US2022185898A1PendingUtilityA1
Methods of use of anti-sortilin antibodies for treating a disease, disorder, or injury
Est. expiryApr 7, 2035(~8.7 yrs left)· nominal 20-yr term from priority
A61K 31/7088A61P 27/02C07K 2317/34A61P 43/00A61P 25/28C07K 2319/32C07K 2319/30A61P 29/00C07K 2317/14A61P 9/10C07K 2317/21A61P 19/02C07K 2317/92C07K 16/286C07K 2317/76C07K 2317/31A61P 25/16A61P 31/04C07K 2317/55C07K 2317/56C07K 16/2863A61P 21/02A61P 25/00A61P 25/08A61P 27/06
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Claims
Abstract
The present disclosure is generally directed to compositions that include antibodies, e.g., monoclonal, chimeric, humanized antibodies, antibody fragments, etc., that specifically bind on or more epitopes within a Sortilin protein, e.g., human Sortilin or a mammalian Sortilin, and use of such compostions in preventing, reducing risk, or treating an individual in need thereof.
Claims
exact text as granted — not AI-modified1 - 93 . (canceled)
94 . A method of decreasing cellular levels of Sortilin in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of an isolated anti-Sortilin antibody, wherein the anti-Sortilin antibody decreases cellular levels of Sortilin, wherein the decrease in cellular levels of Sortilin is a decrease in cell surface levels of Sortilin, a decrease in intracellular levels of Sortilin, or a decrease in total levels of Sortilin.
95 . The method of claim 94 , wherein levels of Sortilin are decreased in the brain, blood, and/or one or more peripheral organs of the individual.
96 . The method of claim 94 , wherein the anti-Sortilin antibody induces Sortilin degradation, Sortilin cleavage, Sortilin internalization, Sortilin down regulation, or any combination thereof.
97 . The method of claim 94 , wherein the anti-Sortilin antibody inhibits interaction between Sortilin and one or more proteins by: a) reducing the effective levels of Sortilin available for interacting with the one or more proteins; b) inducing degradation of Sortilin; or both.
98 . The method of claim 94 , wherein the anti-Sortilin antibody inhibits interaction between Sortilin and pro-nerve growth factor (pro-NGF).
99 . The method of claim 94 , wherein the anti-Sortilin antibody does not inhibit interaction between Sortilin and pro-nerve growth factor (pro-NGF).
100 . The method of claim 94 , wherein the anti-Sortilin antibody binds specifically to human Sortilin.
101 . The method of claim 100 , wherein the anti-Sortilin antibody binds with a dissociation constant (K D ) for human Sortilin that ranges from about 0.005 nM to about 100 nM.
102 . The method of claim 94 , wherein the anti-Sortilin antibody binds specifically to mouse Sortilin.
103 . The method of claim 102 , wherein the anti-Sortilin antibody binds with a dissociation constant (K D ) for mouse Sortilin that ranges from about 0.005 nM to about 100 nM.
104 . The method of claim 94 , wherein the anti-Sortilin antibody inhibits the interaction between Sortilin expressed on a cell and Progranulin.
105 . The method of claim 104 , wherein the anti-Sortilin antibody comprises a light chain variable domain and a heavy chain variable domain, wherein:
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 55, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 129, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 155, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 190; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 55, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 513, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 526, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 190; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 55, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 516, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 527, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 190; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 55, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 520, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 533, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 553; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 55, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 523, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 526, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 190; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 97, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 142, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 169, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 231; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 13, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 33, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 91, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 140, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 166, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 225; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 7, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 31, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 54, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 129, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 155, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 190; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 21, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 95, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 142, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 169, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 229; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 101, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 142, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 169, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 234; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 6, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 89, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 140, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 166, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 223; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 30, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 100, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 142, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 170, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 233; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 11, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 48, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 127, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 152, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 185; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 123, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 148, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 173, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 254; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 85, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 136, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 163, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 219; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 11, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 103, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 142, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 169, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 236; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 46, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 126, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 151, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 183; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 12, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 32, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 112, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 145, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 175, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 244; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 15, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 104, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 142, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 169, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 236; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 30, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 105, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 142, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 169, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 237; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 22, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 106, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 144, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 172, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 238; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 20, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 109, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 144, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 175, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 241; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 13, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 39, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 114, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 145, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 175, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 245; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 24, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 116, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 144, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 173, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 247; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 30, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 121, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 148, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 173, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 252; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 30, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 70, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 136, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 163, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 204; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 16, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 66, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 135, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 161, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 201; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 6, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 84, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 139, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 163, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 218; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 11, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 125, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 149, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 178, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 256; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 64, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 133, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 160, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 199; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 343, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 342; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 343, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 621; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 343, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 624; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 343, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 648; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 343, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 666; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 425, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 426; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 413, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 414; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 341, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 342; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 421, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 422; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 432, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 433; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 409, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 410; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 430, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 431; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 330, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 331; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 474, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 475; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 401, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 402; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 436, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 437; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 326, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 327; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 453, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 454; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 438, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 437; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 439, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 440; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 441, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 442; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 447, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 448; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 457, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 456; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 460, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 461; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 470, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 471; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 371, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 372; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 364, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 365; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 399, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 400; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 478, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 479; or the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 360, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 361.
106 . The method of claim 104 , wherein the anti-Sortilin antibody:
(a) competes with a reference anti-Sortilin antibody for binding to human Sortilin, and/or (b) binds to an epitope of human Sortilin that is the same as the Sortilin epitope bound by a reference anti-Sortilin antibody; wherein the reference anti-Sortilin antibody comprises a light chain variable domain and a heavy chain variable domain, wherein:
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 55, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 129, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 155, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 190;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 55, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 513, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 526, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 190;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 55, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 516, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 527, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 190;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 55, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 520, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 533, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 553;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 55, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 523, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 526, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 190;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 97, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 142, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 169, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 231;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 13, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 33, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 91, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 140, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 166, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 225; the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 7, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 31, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 54, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 129, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 155, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 190; the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 21, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 95, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 142, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 169, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 229; the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 101, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 142, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 169, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 234; the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 6, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 89, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 140, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 166, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 223; the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 30, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 100, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 142, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 170, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 233; the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 11, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 48, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 127, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 152, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 185; the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 123, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 148, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 173, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 254; the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 85, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 136, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 163, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 219; the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 11, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 103, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 142, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 169, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 236;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 46, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 126, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 151, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 183;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 12, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 32, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 112, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 145, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 175, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 244; the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 15, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 104, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 142, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 169, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 236;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 30, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 105, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 142, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 169, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 237;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 22, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 106, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 144, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 172, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 238;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 20, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 109, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 144, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 175, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 241;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 13, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 39, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 114, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 145, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 175, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 245;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 24, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 116, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 144, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 173, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 247;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 30, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 121, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 148, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 173, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 252;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 30, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 70, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 136, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 163, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 204;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 16, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 66, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 135, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 161, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 201;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 6, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 84, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 139, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 163, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 218;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 11, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 125, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 149, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 178, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 256;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 64, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 133, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 160, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 199;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 343, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 342;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 343, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 621;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 343, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 624;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 343, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 648;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 343, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 666;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 425, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 426;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 413, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 414;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 341, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 342;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 421, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 422;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 432, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 433;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 409, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 410;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 430, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 431;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 330, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 331;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 474, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 475;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 401, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 402;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 436, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 437;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 326, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 327;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 453, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 454; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 438, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 437;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 439, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 440;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 441, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 442;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 447, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 448;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 457, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 456;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 460, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 461;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 470, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 471;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 371, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 372;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 364, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 365;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 399, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 400;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 478, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 479; or
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 360, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 361.
107 . The method of claim 94 , wherein the anti-Sortilin antibody does not inhibit the interaction between Sortilin expressed on a cell and Progranulin.
108 . The method of claim 107 , wherein the anti-Sortilin antibody comprises a light chain variable domain and a heavy chain variable domain, wherein:
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 7, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 42, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 126, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 150, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 180; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 7, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 42, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 482, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 493, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 180; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 7, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 42, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 483, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 494, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 180; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 7, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 42, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 486, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 503, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 180; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 7, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 35, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 59, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 130, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 158, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 194; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 122, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 147, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 173, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 253;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 122, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 147, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 598, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 253;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 122, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 593, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 600, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 253;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 122, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 596, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 603, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 253;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 8, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 28, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 62, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 130, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 158, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 197;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 8, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 28, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 62, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 567, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 573, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 197;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 8, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 28, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 62, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 130, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 577, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 197;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 8, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 28, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 62, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 570, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 579, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 197;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 30, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 69, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 135, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 162, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 203; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 60, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 130, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 156, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 195; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 13, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 58, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 130, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 157, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 193; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 30, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 68, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 135, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 162, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 203; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 7, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 61, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 130, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 157, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 196; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 319, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 320; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 319, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 604; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 319, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 605; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 319, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 614; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 350, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 351; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 472, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 473; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 472, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 687; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 472, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 689; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 472, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 692; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 356, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 357; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 356, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 672; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 356, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 676; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 356, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 678; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 370, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 369; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 352, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 353; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 348, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 349; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 368, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 369; or the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 354, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 355.
109 . The method of claim 107 , wherein the anti-Sortilin antibody:
(a) competes with a reference anti-Sortilin antibody for binding to human Sortilin, and/or (b) binds to an epitope of human Sortilin that is the same as the Sortilin epitope bound by a reference anti-Sortilin antibody; wherein the reference anti-Sortilin antibody comprises a light chain variable domain and a heavy chain variable domain, wherein:
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 7, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 42, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 126, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 150, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 180;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 7, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 42, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 482, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 493, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 180;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 7, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 42, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 483, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 494, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 180;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 7, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 42, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 486, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 503, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 180; the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 7, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 35, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 59, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 130, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 158, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 194; the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 122, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 147, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 173, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 253;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 122, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 147, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 598, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 253;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 122, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 593, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 600, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 253;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 122, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 596, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 603, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 253;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 8, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 28, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 62, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 130, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 158, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 197;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 8, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 28, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 62, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 567, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 573, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 197;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 8, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 28, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 62, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 130, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 577, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 197;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 8, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 28, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 62, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 570, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 579, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 197;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 30, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 69, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 135, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 162, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 203; the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 60, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 130, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 156, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 195; the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 13, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 58, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 130, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 157, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 193; the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 30, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 68, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 135, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 162, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 203; the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 7, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 61, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 130, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 157, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 196; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 319, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 320; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 319, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 604; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 319, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 605; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 319, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 614; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 350, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 351; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 472, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 473; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 472, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 687; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 472, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 689; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 472, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 692; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 356, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 357; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 356, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 672; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 356, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 676; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 356, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 678; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 370, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 369; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 352, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 353; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 348, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 349; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 368, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 369; or the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 354, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 355.
110 . The method of claim 94 , wherein the anti-Sortilin antibody increases extracellular levels of Progranulin.
111 . The method of claim 110 , wherein the anti-Sortilin antibody:
(a) induces one or more Progranulin activities; (b) reduces endosomal internalization of Progranulin, or fragments thereof; and/or (c) increases the effective concentration of Progranulin.
112 . The method of claim 110 , wherein the anti-Sortilin antibody comprises a light chain variable domain and a heavy chain variable domain, wherein:
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 7, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 42, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 126, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 150, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 180; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 7, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 42, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 482, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 493, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 180; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 7, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 42, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 483, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 494, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 180; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 7, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 42, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 486, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 503, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 180; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 7, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 35, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 59, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 130, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 158, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 194; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 122, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 147, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 173, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 253;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 122, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 147, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 598, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 253;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 122, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 593, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 600, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 253;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 122, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 596, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 603, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 253;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 8, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 28, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 62, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 130, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 158, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 197;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 8, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 28, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 62, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 567, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 573, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 197;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 8, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 28, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 62, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 130, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 577, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 197;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 8, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 28, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 62, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 570, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 579, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 197;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 30, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 69, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 135, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 162, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 203; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 60, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 130, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 156, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 195;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 55, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 129, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 155, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 190;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 55, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 513, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 526, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 190;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 55, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 516, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 527, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 190;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 55, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 520, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 533, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 553;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 55, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 523, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 526, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 190;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 13, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 58, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 130, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 157, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 193; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 30, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 68, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 135, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 162, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 203; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 7, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 61, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 130, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 157, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 196;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 97, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 142, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 169, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 231;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 13, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 33, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 91, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 140, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 166, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 225; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 7, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 31, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 54, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 129, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 155, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 190; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 21, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 95, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 142, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 169, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 229; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 101, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 142, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 169, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 234; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 6, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 89, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 140, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 166, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 223;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 30, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 100, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 142, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 170, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 233;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 11, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 48, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 127, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 152, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 185;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 123, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 148, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 173, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 254;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 85, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 136, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 163, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 219;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 11, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 103, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 142, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 169, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 236;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 46, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 126, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 151, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 183;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 12, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 32, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 112, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 145, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 175, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 244; the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 15, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 104, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 142, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 169, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 236;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 30, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 105, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 142, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 169, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 237;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 22, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 106, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 144, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 172, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 238;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 13, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 39, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 114, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 145, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 175, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 245;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 24, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 116, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 144, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 173, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 247;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 30, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 121, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 148, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 173, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 252;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 30, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 70, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 136, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 163, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 204;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 16, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 66, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 135, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 161, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 201;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 6, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 84, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 139, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 163, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 218;
the light chain variable domain comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 11, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 125, and the heavy chain variable domain comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 149, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 178, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 256;
the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 319, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 320; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 319, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 604; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 319, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 605; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 319, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 614; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 350, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 351; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 472, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 473; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 472, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 687; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 472, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 689; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 472, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 692; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 356, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 357; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 356, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 672; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 356, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 676; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 356, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 678; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 370, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 369; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 352, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 353; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 343, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 342; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 343, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 621; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 343, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 624; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 343, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 648; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 343, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 666; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 348, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 349; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 368, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 369; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 354, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 355; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 425, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 426; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 413, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 414; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 341, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 342; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 421, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 422; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 432, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 433; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 409, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 410;
the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 430, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 431;
the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 330, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 331;
the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 474, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 475;
the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 401, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 402;
the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 436, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 437;
the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 326, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 327;
the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 453, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 454; the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 438, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 437;
the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 439, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 440;
the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 441, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 442;
the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 457, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 456;
the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 460, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 461;
the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 470, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 471;
the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 371, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 372;
the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 364, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 365;
the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 399, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 400; or
the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 478, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 479.
113 . The method of claim 110 , wherein the anti-Sortilin antibody:
(a) competes with a reference anti-Sortilin antibody for binding to human Sortilin, and/or (b) binds to an epitope of human Sortilin that is the same as the Sortilin epitope bound by a reference anti-Sortilin antibody; wherein the reference anti-Sortilin antibody comprises a light chain variable domain and a heavy chain variable domain, wherein:
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 7, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 42, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 126, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 150, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 180;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 7, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 42, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 482, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 493, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 180;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 7, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 42, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 483, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 494, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 180;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 7, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 42, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 486, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 503, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 180; the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 7, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 35, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 59, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 130, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 158, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 194; the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 122, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 147, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 173, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 253;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 122, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 147, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 598, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 253;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 122, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 593, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 600, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 253;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 122, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 596, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 603, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 253;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 8, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 28, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 62, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 130, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 158, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 197;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 8, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 28, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 62, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 567, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 573, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 197;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 8, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 28, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 62, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 130, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 577, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 197;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 8, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 28, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 62, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 570, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 579, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 197;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 30, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 69, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 135, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 162, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 203; the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 60, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 130, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 156, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 195;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 55, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 129, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 155, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 190;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 55, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 513, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 526, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 190; the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 55, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 516, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 527, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 190; the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 55, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 520, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 533, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 553; the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 55, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 523, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 526, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 190; the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 13, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 58, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 130, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 157, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 193; the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 30, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 68, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 135, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 162, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 203; the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 7, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 61, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 130, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 157, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 196; the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 97, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 142, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 169, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 231; the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 13, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 33, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 91, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 140, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 166, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 225; the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 7, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 31, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 54, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 129, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 155, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 190; the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 21, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 95, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 142, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 169, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 229; the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 101, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 142, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 169, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 234; the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 6, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 89, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 140, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 166, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 223;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 30, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 100, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 142, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 170, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 233;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 11, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 48, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 127, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 152, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 185;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 123, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 148, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 173, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 254;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 85, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 136, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 163, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 219;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 11, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 103, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 142, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 169, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 236;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 29, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 46, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 126, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 151, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 183;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 12, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 32, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 112, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 145, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 175, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 244; the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 15, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 104, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 142, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 169, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 236;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 30, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 105, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 142, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 169, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 237;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 22, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 106, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 144, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 172, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 238;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 13, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 39, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 114, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 145, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 175, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 245;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 24, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 116, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 144, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 173, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 247;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 30, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 121, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 148, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 173, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 252;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 30, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 70, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 136, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 163, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 204;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 16, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 27, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 66, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 135, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 161, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 201;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 6, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 84, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 139, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 163, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 218;
the light chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 11, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 125, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 149, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 178, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 256;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 319, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 320; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 319, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 604; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 319, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 605; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 319, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 614; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 350, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 351; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 472, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 473; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 472, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 687; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 472, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 689; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 472, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 692; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 356, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 357; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 356, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 672; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 356, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 676; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 356, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 678; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 370, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 369; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 352, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 353;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 343, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 342;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 343, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 621;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 343, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 624;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 343, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 648;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 343, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 666;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 348, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 349; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 368, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 369; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 354, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 355;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 425, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 426;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 413, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 414; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 341, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 342; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 421, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 422; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 432, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 433; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 409, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 410;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 430, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 431;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 330, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 331;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 474, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 475;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 401, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 402;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 436, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 437;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 326, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 327;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 453, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 454; the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 438, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 437;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 439, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 440;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 441, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 442;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 457, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 456;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 460, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 461;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 470, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 471;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 371, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 372;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 364, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 365;
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 399, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 400; or
the light chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 478, and the heavy chain variable domain of the reference anti-Sortilin antibody comprises the amino acid sequence of SEQ ID NO: 479.
114 . The method of claim 94 , wherein the anti-Sortilin antibody is a human antibody, a humanized antibody, a bispecific antibody, a monoclonal antibody, a multivalent antibody, a conjugated antibody, or a chimeric antibody.
115 . The method of claim 94 , wherein the anti-Sortilin antibody is a multivalent antibody recognizing a second antigen.
116 . The method of claim 115 , wherein the second antigen is an antigen facilitating transport across the blood-brain-barrier.
117 . The method of claim 116 , wherein the second antigen is selected from the group consisting of transferrin receptor (TR), insulin receptor (HIR), insulin-like growth factor receptor (IGFR), low-density lipoprotein receptor related proteins 1 and 2 (LPR-1 and 2), diphtheria toxin receptor, CRM197, TMEM 30(A), a protein transduction domain, TAT, Syn-B, penetratin, a poly-arginine peptide, an angiopep peptide, and ANG1005.
118 . The method of claim 94 , wherein the anti-Sortilin antibody is an antibody fragment that binds to an epitope comprising amino acid residues on human Sortilin or a mammalian Sortilin protein, and wherein the antibody fragment is an Fab, Fab′, Fab′-SH, F(ab′)2, Fv, or scFv fragment.
119 . The method of claim 94 , wherein the anti-Sortilin antibody has an IgG1 or IgG4 isotype.
120 . The method of claim 119 , wherein:
(a) the anti-Sortilin antibody has a human IgG1 isotype and comprises one or more amino acid substitutions in the Fc region at a residue position selected from the group consisting of: N297A, N297Q, D265A, L234A, L235A, C226S, C229S, P238S, E233P, L234V, P238A, A327Q, A327G, P329A, K322A, L234F, L235E, P331S, T394D, A330L, M252Y, S254T, T256E, and any combination thereof, wherein the numbering of the residues is according to EU numbering; or (b) the anti-Sortilin antibody has a human IgG4 isotype and comprises one or more amino acid substitutions in the Fc region at a residue position selected from the group consisting of: E233P, F234V, L234A/F234A, L235A, G237A, E318A, S228P, L236E, S241P, L248E, T394D, M252Y, S254T, T256E, N297A, N297Q, and any combination thereof, wherein the numbering of the residues is according to EU numbering.
121 . The method of claim 120 , wherein:
(a) the IgG1 Fc region further comprises one or more additional amino acid substitutions at a position selected from the group consisting of A330L, L234F, L235E, P331S, and any combination thereof, wherein the numbering of the residues is according to EU numbering; (b) the IgG1 or IgG4 Fc region further comprises one or more additional amino acid substitutions at a position selected from the group consisting of M252Y, S254T, T256E, and any combination thereof, wherein the numbering of the residues is according to EU numbering; or (c) the IgG4 Fc region further comprises a S228P amino acid substitution according to EU numbering.
122 . The method of claim 119 , wherein: (a) the anti-Sortilin antibody has a human IgG4 isotype and comprises an amino acid substitution at residue positions S228P, F234A, and L235A, wherein the numbering of the residue position is according to EU numbering; or (b) the anti-Sortilin antibody has a human IgG1 isotype and comprises an amino acid substitution at residue positions L234A, L235A, and P331S, wherein the numbering of the residue position is according to EU numbering.Cited by (0)
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