Modulators and methods of use

Patent metadata

Field	Value
Publication number	US-10017565-B2
Application number	US-201615250151-A
Country	US
Kind code	B2
Filing date	Aug 29, 2016
Priority date	Sep 3, 2010
Publication date	Jul 10, 2018
Grant date	Jul 10, 2018

Abstract

Novel modulators, including antibodies and derivatives thereof, and methods of using such modulators to treat hyperproliferative disorders are provided.

First claim

The invention claimed is:

1. A method of reducing the frequency of tumor initiating cells in a subject in need thereof comprising administering an isolated anti-CD46 antibody or immunoreactive fragment thereof, wherein the antibody or immunoreactive fragment thereof is selected from the group consisting of:
a) an antibody comprising three heavy chain complementarity determining regions set forth as residues 31-35 of SEQ ID NO: 15 for CDR-H1, residues 50-65 of SEQ ID NO: 15 for CDR-H2, and residues 95-102 of SEQ ID NO: 15 for CDR-H3, and comprising three light chain complementarity determining regions set forth as residues 24-34 of SEQ ID NO: 17 for CDR-L1, residues 50-56 of SEQ ID NO: 17 for CDR-L2 and residues 89-97 of SEQ ID NO: 17 for CDR-L3, wherein the residues are numbered according to Kabat;
b) an antibody comprising three heavy chain complementarity determining regions set forth as residues 31-35 of SEQ ID NO: 19 for CDR-H1, residues 50-65 of SEQ ID NO: 19 for CDR-H2, and residues 95-102 of SEQ ID NO: 19 for CDR-H3, and comprising three light chain complementarity determining regions set forth as residues 24-34 of SEQ ID NO: 21 for CDR-L1, residues 50-56 of SEQ ID NO: 21 for CDR-L2 and residues 89-97 of SEQ ID NO: 21 for CDR-L3, wherein the residues are numbered according to Kabat;
c) an antibody comprising three heavy chain complementarity determining regions set forth as residues 31-35 of SEQ ID NO: 23 for CDR-H1, residues 50-65 of SEQ ID NO: 23 for CDR-H2, and residues 95-102 of SEQ ID NO: 23 for CDR-H3, and comprising three light chain complementarity determining regions set forth as residues 24-34 of SEQ ID NO: 25 for CDR-L1, residues 50-56 of SEQ ID NO: 25 for CDR-L2 and residues 89-97 of SEQ ID NO: 25 for CDR-L3, wherein the residues are numbered according to Kabat;
d) an antibody comprising three heavy chain complementarity determining regions set forth as residues 31-35 of SEQ ID NO: 27 for CDR-H1, residues 50-65 of SEQ ID NO: 27 for CDR-H2, and residues 95-102 of SEQ ID NO: 27 for CDR-H3, and comprising three light chain complementarity determining regions set forth as residues 24-34 of SEQ ID NO: 29 for CDR-L1, residues 50-56 of SEQ ID NO: 29 for CDR-L2 and residues 89-97 of SEQ ID NO: 29 for CDR-L3, wherein the residues are numbered according to Kabat;
e) an antibody comprising three heavy chain complementarity determining regions set forth as residues 31-35 of the polypeptide encoded by the polynucleotide set forth as SEQ ID NO: 30 for CDR-H1, residues 50-65 of the polypeptide encoded by the polynucleotide set forth as SEQ ID NO: 30 for CDR-H2, and residues 95-102 of the polypeptide encoded by the polynucleotide set forth as SEQ ID NO: 30 for CDR-H3, and comprising three light chain complementarity determining regions set forth as residues 24-34 of SEQ ID NO: 33 for CDR-L1, residues 50-56 of SEQ ID NO: 33 for CDR-L2 and residues 89-97 of SEQ ID NO: 33 for CDR-L3, wherein the residues are numbered according to Kabat;
f) an antibody comprising three heavy chain complementarity determining regions set forth as residues 31-35 of SEQ ID NO: 35 for CDR-H1, residues 50-65 of SEQ ID NO: 35 for CDR-H2, and residues 95-102 of SEQ ID NO: 35 for CDR-H3, and comprising three light chain complementarity determining regions set forth as residues 24-34 of SEQ ID NO: 37 for CDR-L1, residues 50-56 of SEQ ID NO: 37 for CDR-L2 and residues 89-97 of SEQ ID NO: 37 for CDR-L3, wherein the residues are numbered according to Kabat;
g) an antibody comprising three heavy chain complementarity determining regions set forth as residues 31-35 of SEQ ID NO: 39 for CDR-H1, residues 50-65 of SEQ ID NO: 39 for CDR-H2, and residues 95-102 of SEQ ID NO: 39 for CDR-H3, and comprising three light chain complementarity determining regions set forth as residues 24-34 of SEQ ID NO: 41 for CDR-L1, residues 50-56 of SEQ ID NO: 41 for CDR-L2 and residues 89-97 of SEQ ID NO: 41 for CDR-L3, wherein the residues are numbered according to Kabat;
h) an antibody comprising three heavy chain complementarity determining regions set forth as residues 31-35 of SEQ ID NO: 43 for CDR-H1, residues 50-65 of SEQ ID NO: 43 for CDR-H2, and residues 95-102 of SEQ ID NO: 43 for CDR-H3, and comprising three light chain complementarity determining regions set forth as residues 24-34 of SEQ ID NO: 45 for CDR-L1, residues 50-56 of SEQ ID NO: 45 for CDR-L2 and residues 89-97 of SEQ ID NO: 45 for CDR-L3, wherein the residues are numbered according to Kabat;
i) an antibody comprising three heavy chain complementarity determining regions set forth as residues 31-35 of SEQ ID NO: 47 for CDR-H1, residues 50-65 of SEQ ID NO: 47 for CDR-H2, and residues 95-102 of SEQ ID NO: 47 for CDR-H3, and comprising three light chain complementarity determining regions set forth as residues 24-34 of SEQ ID NO: 49 for CDR-L1, residues 50-56 of SEQ ID NO: 49 for CDR-L2 and residues 89-97 of SEQ ID NO: 49 for CDR-L3, wherein the residues are numbered according to Kabat;
j) an antibody comprising three heavy chain complementarity determining regions set forth as residues 31-35 of SEQ ID NO: 51 for CDR-H1, residues 50-65 of SEQ ID NO: 51 for CDR-H2, and residues 95-102 of SEQ ID NO: 51 for CDR-H3, and comprising three light chain complementarity determining regions set forth as residues 24-34 of SEQ ID NO: 53 for CDR-L1, residues 50-56 of SEQ ID NO: 53 for CDR-L2 and residues 89-97 of SEQ ID NO: 53 for CDR-L3, wherein the residues are numbered according to Kabat;
k) an antibody comprising three heavy chain complementarity determining regions set forth as residues 31-35 of SEQ ID NO: 55 for CDR-H1, residues 50-65 of SEQ ID NO: 55 for CDR-H2, and residues 95-102 of SEQ ID NO: 55 for CDR-H3, and comprising three light chain complementarity determining regions set forth as residues 24-34 of SEQ ID NO: 57 for CDR-L1, residues 50-56 of SEQ ID NO: 57 for CDR-L2 and residues 89-97 of SEQ ID NO: 57 for CDR-L3, wherein the residues are numbered according to Kabat;
l) an antibody comprising three heavy chain complementarity determining regions set forth as residues 31-35 of SEQ ID NO: 59 for CDR-H1, residues 50-65 of SEQ ID NO: 59 for CDR-H2, and residues 95-102 of SEQ ID NO: 59 for CDR-H3, and comprising three light chain complementarity determining regions set forth as residues 24-34 of SEQ ID NO: 61 for CDR-L1, residues 50-56 of SEQ ID NO: 61 for CDR-L2 and residues 89-97 of SEQ ID NO: 61 for CDR-L3, wherein the residues are numbered according to Kabat;
m) an antibody comprising three heavy chain complementarity determining regions set forth as residues 31-35 of SEQ ID NO: 63 for CDR-H1, residues 50-65 of SEQ ID NO: 63 for CDR-H2, and residues 95-102 of SEQ ID NO: 63 for CDR-H3, and comprising three light chain complementarity determining regions set forth as residues 24-34 of SEQ ID NO: 65 for CDR-L1, residues 50-56 of SEQ ID NO: 65 for CDR-L2 and residues 89-97 of SEQ ID NO: 65 for CDR-L3, wherein the residues are numbered according to Kabat;
n) an antibody comprising three heavy chain complementarity determining regions set forth as residues 31-35 of SEQ ID NO: 67 for CDR-H1, residues 50-65 of SEQ ID NO: 67 for CDR-H2, and residues 95-102 of SEQ ID NO: 67 for CDR-H3, and comprising three light chain complementarity determining regions set forth as residues 24-34 of SEQ ID NO: 69 for CDR-L1, residues 50-56 of SEQ ID NO: 69 for CDR-L2 and residues 89-97 of SEQ ID NO: 69 for CDR-L3, wherein the residues are numbered according to Kabat;
o) an antibody comprising three heavy chain complementarity determining regions set forth as residues 31-35 of SEQ ID NO: 71 for CDR-H1, residues 50-65 of SEQ ID NO: 71 for CDR-H2, and residues 95-102 of SEQ ID NO: 71 for CDR-H3, and comprising three light chain complementarity determining regions set forth as residues 24-34 of SEQ ID NO: 73 for CDR-L1, residues 50-56 of SEQ ID NO: 73 for CDR-L2 and residues 89-97 of SEQ ID NO: 73 for CDR-L3, wherein th

Assignees

• Abbvie Stemcentrx Llc

Inventors

• Dylla Scott J
• Foord Orit
• Stull Robert A
• Anderson Wade C
• Ohshima Saiyou

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/04

  specific for metastasis · CPC title

• A61K39/39558

  against tumor tissues, cells, antigens · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title