Anti-ror1 antibodies

Abstract

The invention relates to antibodies, and in particular, to antibodies exhibiting specificity for Receptor tyrosine kinase-like Orphan Receptors (ROR), and to uses thereof, for example in the treatment of cancer. The invention extends to polynucleotide and polypeptide sequences encoding the antibodies, and therapeutic uses thereof, and to diagnostic kits comprising these molecules. The invention also extends to antibody-drug conjugates and to uses thereof in therapy.

1 .- 44 . (canceled) 
     
     
         45 . A polypeptide capable of binding to Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR1) protein, the peptide comprising an amino acid sequence selected from a group consisting of:
 (i) SEQ ID NO:8, 9, 10, 16, 17 and/or 18;   (ii) SEQ ID NO:24, 25, 26, 32, 33 and/or 34;   (iii) SEQ ID NO:40, 41, 42, 48, 49 and/or 50;   (iv) SEQ ID NO:56, 57, 58, 64, 65 and/or 66;   (v) SEQ ID NO:72, 73, 74, 80, 81 and/or 82;   (vi) SEQ ID NO:88, 89, 90, 96, 97 and/or 98;   (vii) SEQ ID NO:104, 105, 106, 112, 113 and/or 114;   (viii) SEQ ID NO:120, 121, 122, 128, 129 and/or 130;   (ix) SEQ ID NO:136, 137, 138, 144, 145 and/or 146;   (x) SEQ ID NO:152, 153, 154, 160, 161 and/or 162;   (xi) SEQ ID NO:168, 169, 170, 176, 177 and/or 178;   (xii) SEQ ID NO:184, 185, 186, 192, 193 and/or 194;   (xiii) SEQ ID NO:200, 201, 202, 208, 209 and/or 210; and/or   (xiv) SEQ ID NO:216, 217, 218, 224, 225 and/or 226.   
     
     
         46 . The polypeptide of  claim 45 , comprising a functional fragment of an anti-ROR1 antibody. 
     
     
         47 . The polypeptide of  claim 46 , comprising an anti-ROR1 scFv. 
     
     
         48 . The polypeptide of  claim 45 , comprising at least two, three, four, five or six amino acid sequences defined in any of (i) to (xiv). 
     
     
         49 . The polypeptide according to  claim 45 , wherein the peptide comprises an amino acid sequence substantially as set out in SEQ ID NO: 4, 20, 36, 52, 68, 84, 100, 116, 132, 148, 164, 180, 196 or 212, or a functional variant or fragment thereof, or an amino acid sequence substantially as set out in SEQ ID NO: 12, 28, 44, 60, 76, 92, 108, 124, 140, 156, 172, 188, 204 or 220, or a functional variant or fragment thereof. 
     
     
         50 . A composition comprising a polypeptide of  claim 45 , optionally derivatized, and a pharmaceutically acceptable vehicle. 
     
     
         51 . A nucleic acid encoding the polypeptide of  claim 45 . 
     
     
         52 . The nucleic acid of  claim 51 , comprising a polynucleotide sequence selected from a group consisting of:
 (i) SEQ ID NO:5, 6, 7, 13, 14 and/or 15;   (ii) SEQ ID NO:21, 22, 23, 29, 30 and/or 31;   (iii) SEQ ID NO:37, 38, 39, 45, 46 and/or 47;   (iv) SEQ ID NO:53, 54, 55, 61, 62 and/or 63;   (v) SEQ ID NO:69, 70, 71, 77, 78 and/or 79;   (vi) SEQ ID NO:85, 86, 87, 93, 94 and/or 95;   (vii) SEQ ID NO:101, 102, 103, 109, 110 and/or 111;   (viii) SEQ ID NO:117, 118, 119, 125, 126 and/or 127;   (ix) SEQ ID NO:133, 134, 135, 141, 142 and/or 143;   (x) SEQ ID NO:149, 150, 151, 157, 158 and/or 159;   (xi) SEQ ID NO:165, 166, 167, 173, 174 and/or 175;   (xii) SEQ ID NO:181, 182, 183, 189, 190 and/or 191;   (xiii) SEQ ID NO:197, 198, 199, 205, 206 and/or 207; and/or   (xiv) SEQ ID NO:213, 214, 215, 221, 222 and/or 223.   
     
     
         53 . The nucleic acid of  claim 52 , wherein the nucleic acid comprises a nucleotide sequence substantially as set out in SEQ ID NO:3, 19, 35, 51, 67, 83, 99, 115, 131, 147, 163, 179, 195 or 211, or a functional variant or fragment thereof, or a nucleotide sequence substantially as set out in SEQ ID NO:11, 27, 43, 59, 75, 91, 107, 123, 139, 155, 171, 187, 203 or 219, or a functional variant or fragment thereof. 
     
     
         54 . A genetic construct comprising the nucleic acid of  claim 50 . 
     
     
         55 . A recombinant vector comprising the genetic construct of  claim 54 . 
     
     
         56 . A host cell comprising the genetic construct of  claim 54 . 
     
     
         57 . A host cell comprising the polypeptide of  claim 45 . 
     
     
         58 . A composition comprising the nucleic acid of  claim 51  and a pharmaceutically acceptable vehicle. 
     
     
         59 . A method of treating, preventing or ameliorating cancer in a subject, the method comprising administering, to a patient in need of such treatment, a therapeutically effective amount of the polypeptide of  claim 45  or the nucleic acid of  claim 51 , each being optionally derivatized. 
     
     
         60 . The method of  claim 59 , wherein the polypeptide or nucleic acid is used in the treatment, prevention, or amelioration of a ROR1-positive cancer type. 
     
     
         61 . The method of  claim 59 , wherein the cancer is chronic lymphocytic leukemia (CLL); mantle cell lymphoma (MCL); B-cell acute lymphoblastic leukemia (B-ALL); marginal zone lymphoma (MZL); neuroblastoma; renal cancer; lung cancer; or breast cancer.