US2021128742A1PendingUtilityA1
CD123 Antibodies and Conjugates Thereof
Est. expiryJun 12, 2035(~8.9 yrs left)· nominal 20-yr term from priority
A61K 47/68035C07K 2317/52C07K 2317/21C07K 2317/14A61K 2039/505A61P 35/02C07K 16/30A61K 39/395A61K 47/6803C07K 2317/56C07K 2317/24C07K 2317/73C07K 2317/92C07K 16/2866A61K 31/5517A61K 9/08A61K 47/6849A61K 47/6851A61K 31/5513A61P 35/00
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Claims
Abstract
The invention provides murine, chimeric, and humanized antibodies that specifically bind to CD123 and conjugates thereof.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . An anti-CD123 antibody-drug conjugate compound having the formula:
or a pharmaceutically salt, solvate, or solvate of the salt; wherein
the subscript n is 1 or 3;
the subscript m is 2 to 5
Ab is an anti-CD123 intact antibody or antigen binding fragment thereof comprising a heavy chain variable region having the amino acid sequence set forth in SEQ ID NO:1; and a light chain variable region having the amino acid sequence set forth in SEQ ID NO:2;
the subscript p is an integer from 1 to 4.
2 . The compound of claim 1 having the formula:
or a pharmaceutically salt, solvate, or solvate of the salt.
3 . The compound of claim 1 having the formula:
or a pharmaceutically salt, solvate, or solvate of the salt.
4 . The compound of any one of claims 1 to 3 wherein n is 1.
5 . The compound of any one of claims 1 to 3 wherein n is 3.
6 . The compound of any one of claims 1 to 5 wherein m is 5.
7 . The compound of any one of claims 1 to 6 wherein attachment to Ab is via a sulfur atom of an engineered cysteine residue of Ab.
8 . The compound of any one of the preceding claims wherein Ab comprises a heavy chain variable region having the amino acid sequence set forth in SEQ ID NO:1 fused to a human heavy chain constant region; and a light chain variable region having the amino acid sequence set forth in SEQ ID NO:2 fused to a human light chain constant region.
9 . The compound of claim 8 wherein Ab comprises a heavy chain having the amino acid sequence set forth in SEQ ID NO:3 and a light chain having the amino acid sequence set forth in SEQ ID NO:4 and attachment to Ab is via a sulfur atom or an engineered cysteine residue at position 239 of the heavy chain constant region, according to the EU index system of numbering.
10 . The compound of any one of the preceding claims wherein p is 2.
11 . A pharmaceutical composition comprising a population of anti-CD123 antibody-drug conjugate molecules having the formula:
or a pharmaceutically salt, solvate, or solvate of the salt; wherein
the subscript n is 1 to 3;
the subscript m is 2 to 5
Ab is an anti-CD123 intact antibody or antigen binding fragment thereof comprising a heavy chain variable region having the amino acid sequence set forth in SEQ ID NO:1; and a light chain variable region having the amino acid sequence set forth in SEQ ID NO:2;
the subscript p is an integer from 1 to 4; and the average drug load of the composition is about 2.
12 . The pharmaceutical composition of claim 11 wherein the antibody-drug conjugate molecules have the formula:
or a pharmaceutically salt, solvate, or solvate of the salt.
13 . The pharmaceutical composition of claim 11 wherein the antibody-drug conjugate molecules have the formula:
or a pharmaceutically salt, solvate, or solvate of the salt.
14 . The pharmaceutical compositions of any one of claims 11 to 13 wherein n is 1.
15 . The pharmaceutical compositions of any one of claims 11 to 13 wherein n is 3.
16 . The pharmaceutical composition of any one of claims 11 to 15 wherein m is 5.
17 . The pharmaceutical composition of any one of claims 11 to 16 wherein attachment to Ab is via a sulfur atom of an engineered cysteine residue of Ab.
18 . The pharmaceutical composition of any one of the preceding claims wherein Ab comprises a heavy chain variable region having the amino acid sequence set forth in SEQ ID NO:1 fused to a human heavy chain constant region; and a light chain variable region having the amino acid sequence set forth in SEQ ID NO:2 fused to a human light chain constant region.
19 . The pharmaceutical composition of claim 18 wherein Ab comprises a heavy chain having the amino acid sequence set forth in SEQ ID NO:3 and a light chain having the amino acid sequence set forth in SEQ ID NO:4 and attachment to Ab is via a sulfur atom or an engineered cysteine residue at position 239 of the heavy chain constant region, according to the EU index system of numbering.
20 . The pharmaceutical composition of any one of claims 11 to 19 wherein p is 1 or 2.
21 . The pharmaceutical composition of any one of claims 11 to 20 in aqueous form.
22 . The pharmaceutical composition of any one of claims 11 to 20 in lyophilized form.
23 . An antibody-drug conjugate composition comprising a population of anti-CD123 antibody-drug conjugate molecules having the formula:
or a pharmaceutically salt, solvate, or solvate of the salt; wherein
the subscript n is 1 to 3;
the subscript m is 2 to 5
Ab is an anti-CD123 intact antibody or antigen binding fragment thereof comprising a heavy chain variable region having the amino acid sequence set forth in SEQ ID NO:1; and a light chain variable region having the amino acid sequence set forth in SEQ ID NO:2; and
the subscript p is an integer from 1 to 4; and the average drug load of the composition is about 2.
24 . The composition of claim 23 wherein the antibody-drug conjugate molecules have the formula:
or a pharmaceutically salt, solvate, or solvate of the salt.
25 . The composition of claim 23 wherein the antibody-drug conjugate molecules have the formula:
or a pharmaceutically salt, solvate, or solvate of the salt.
26 . The compositions of any one of claims 23 to 25 wherein n is 1.
27 . The compositions of any one of claims 23 to 25 wherein n is 3.
28 . The composition of any one of claims 23 to 27 wherein m is 5.
29 . The composition of any one of claims 23 to 28 wherein attachment to Ab is via a sulfur atom of an engineered cysteine residue of Ab.
30 . The composition of any one of claims 23 to 29 wherein Ab comprises a heavy chain variable region having the amino acid sequence set forth in SEQ ID NO:1 fused to a human heavy chain constant region; and a light chain variable region having the amino acid sequence set forth in SEQ ID NO:2 fused to a human light chain constant region.
31 . The composition of claim 30 wherein Ab comprising a heavy chain having the amino acid sequence set forth in SEQ ID NO:3 and a light chain having the amino acid sequence set forth in SEQ ID NO:4 and attachment to Ab is via a sulfur atom or an engineered cysteine residue at position 239 of the heavy chain constant region, according to the EU index system of numbering
32 . An anti-CD123 intact antibody or antigen binding fragment thereof comprising a heavy chain variable region having the amino acid sequence set forth in SEQ ID NO:1; and a light chain variable region having the amino acid sequence set forth in SEQ ID NO:2.
33 . The antibody of claim 32 wherein the heavy chain variable region is fused to a heavy chain constant region; and the light chain variable region is fused to a light chain constant region.
34 . The antibody of claim 32 comprising a heavy chain having the amino acid sequence set forth in SEQ ID NO:3 and a light chain having the amino acid sequence set forth in SEQ ID NO:4.
35 . A method of treating a patient having a cancer that expresses CD123, comprising administering to the patient an effective regimen of a pharmaceutical composition of any one of claims 11 to 21 .
36 . The method of claim 35 wherein the cancer is acute myeloid leukemia (AML).
37 . The method of claim 35 wherein the cancer is myelodysplastic syndrome (MDS), B-cell acute lymphoblastic leukemia (B-ALL), hairy cell leukemia, Fanconi anemia, Blastic plasmacytoid dendritic cell neoplasm (BPDCN), Hodgkin's disease, Immature T-cell acute lymphoblastic leukemia (Immature T-ALL), Burkitt's lymphoma, Follicular lymphoma, chronic lymphocytic leukemia (CLL), or mantle cell lymphoma.
38 . The intact antibody or antigen binding fragment of any one of claims 32 - 34 conjugated to a cytotoxic agent.
39 . The intact antibody or antigen binding fragment of claim 38 wherein the cytotoxic agent is a maytansinoid, auristatin, pyrrolo[1,4]benzodiazepine, indolinobenzodiazepine, or oxazolidinobenzodiazepine.
40 . A pharmaceutical composition comprising the intact antibody or antigen binding fragment thereof of claim 38 or 39 .
41 . An anti-CD123 intact antibody or antigen binding fragment thereof comprising a heavy chain variable region having the amino acid sequence set forth in SEQ ID NO:1 provided that H20 is occupied by M or V, H38 is occupied by K or R, H48 is occupied by I, H66 is occupied by K or R, H67 is occupied by A, H69 is occupied by L, H71 is occupied by V, H73 is occupied by R, H81 is occupied by E or H, H82A is occupied by S or N, and H93 is occupied by T; and a light chain variable region having the amino acid sequence set forth in SEQ ID NO:2 provided that L2 is occupied by F, L19 is occupied by A or V, L21 is occupied by I or M, L22 is occupied by N or S, L38 is occupied by L.
42 . The intact antibody or antigen binding fragment thereof of claim 41 that is HALA, HALB, HBLA, HBLB, or HCLB.
43 . The antibody of claim 41 or 42 wherein the heavy chain variable region is fused to a heavy chain constant region; and the light chain variable region is fused to a light chain constant region.
44 . The intact antibody or antigen binding fragment of any one of claims 41 - 43 conjugated to a cytotoxic agent.
45 . The intact antibody or antigen binding fragment of claim 44 wherein the cytotoxic agent is a maytansinoid, auristatin, pyrrolo[1,4]benzodiazepine, indolinobenzodiazepine, or oxazolidinobenzodiazepine.
46 . The intact antibody or antigen binding fragment of claim 45 wherein the cytotoxic agent is
wherein the subscript n is 1 or 3; or a pharmaceutically acceptable salt, solvate, or solvate of the salt thereof.
47 . A pharmaceutical composition comprising the intact antibody or antigen binding fragment thereof of claim 44 or 45 or 46 .Join the waitlist — get patent alerts
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