Polynucleotides encoding anti-kit antibodies

Patent metadata

Field	Value
Publication number	US-9605081-B2
Application number	US-201615084715-A
Country	US
Kind code	B2
Filing date	Mar 30, 2016
Priority date	Jul 25, 2012
Publication date	Mar 28, 2017
Grant date	Mar 28, 2017

Abstract

Provided herein, in one aspect, are antibodies that immunospecifically bind to a human KIT antigen comprising the fourth and/or fifth extracellular Ig-like domains (that is, D4 and/or D5 domains), polynucleotides comprising nucleotide sequences encoding such antibodies, and expression vectors and host cells for producing such antibodies. The antibodies can inhibit KIT activity, such as ligand-induced receptor phosphorylation. Also provided herein are kits and pharmaceutical compositions comprising antibodies that specifically bind to a KIT antigen, as well as methods of treating or managing a KIT-associated disorder or disease and methods of diagnosing a KIT-associated disorder or disease using the antibodies described herein.

First claim

The invention claimed is:

1. A polynucleotide comprising nucleotide sequences encoding a heavy chain variable region (“VH”), a light chain variable region (“VL”), or both a VL and a VH, of an antibody which immunospecifically binds to a D4 region of human KIT, wherein
(i) the VL comprises the amino acid sequence of SEQ ID NO: 8 and the VH comprises the amino acid sequence of SEQ ID NO: 4;
(ii) the VL comprises the amino acid sequence of SEQ ID NO: 10 and the VH comprises the amino acid sequence of SEQ ID NO: 3;
(iii) the VL comprises the amino acid sequence of SEQ ID NO: 8 and the VH comprises the amino acid sequence of SEQ ID NO: 6;
(iv) the VL comprises the amino acid sequence of SEQ ID NO: 7 and the VH comprises the amino acid sequence of SEQ ID NO: 5;
(v) the VL comprises the amino acid sequence of SEQ ID NO: 7 and the VH comprises the amino acid sequence of SEQ ID NO: 2;
(vi) the VL comprises the amino acid sequence of SEQ ID NO: 7 and the VH comprises the amino acid sequence of SEQ ID NO: 3;
(vii) the VL comprises the amino acid sequence of SEQ ID NO: 7 and the VH comprises the amino acid sequence of SEQ ID NO: 4;
(viii) the VL comprises the amino acid sequence of SEQ ID NO: 7 and the VH comprises the amino acid sequence of SEQ ID NO: 6;
(ix) the VL comprises the amino acid sequence of SEQ ID NO: 8 and the VH comprises the amino acid sequence of SEQ ID NO: 2;
(x) the VL comprises the amino acid sequence of SEQ ID NO: 8 and the VH comprises the amino acid sequence of SEQ ID NO: 3;
(xi) the VL comprises the amino acid sequence of SEQ ID NO: 8 and the VH comprises the amino acid sequence of SEQ ID NO: 5;
(xii) the VL comprises the amino acid sequence of SEQ ID NO: 9 and the VH comprises the amino acid sequence of SEQ ID NO: 2;
(xiii) the VL comprises the amino acid sequence of SEQ ID NO: 9 and the VH comprises the amino acid sequence of SEQ ID NO: 3;
(xiv) the VL comprises the amino acid sequence of SEQ ID NO: 9 and the VH comprises the amino acid sequence of SEQ ID NO: 4;
(xv) the VL comprises the amino acid sequence of SEQ ID NO: 9 and the VH comprises the amino acid sequence of SEQ ID NO: 5;
(xvi) the VL comprises the amino acid sequence of SEQ ID NO: 9 and the VH comprises the amino acid sequence of SEQ ID NO: 6;
(xvii) the VL comprises the amino acid sequence of SEQ ID NO: 10 and the VH comprises the amino acid sequence of SEQ ID NO: 2;
(xviii) the VL comprises the amino acid sequence of SEQ ID NO: 10 and the VH comprises the amino acid sequence of SEQ ID NO: 4;
(xix) the VL comprises the amino acid sequence of SEQ ID NO: 10 and the VH comprises the amino acid sequence of SEQ ID NO: 5; or
(xx) the VL comprises the amino acid sequence of SEQ ID NO: 10 and the VH comprises the amino acid sequence of SEQ ID NO: 6.

2. A vector comprising the polynucleotide of claim 1 .

3. A host cell comprising the polynucleotide of claim 1 .

4. A method of making an antibody which immunospecifically binds to a D4 region of human KIT comprising culturing, and/or expressing the antibody in the host cell of claim 3 .

5. A polynucleotide comprising nucleotide sequences encoding a VH, a VL, or both a VL and a VH, of an antibody which immunospecifically binds to a D4 region of human KIT, wherein said antibody comprises:
(i) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 comprising the amino acid sequences of SEQ ID NOs: 19, 20, and 21, respectively; and a VH comprising the amino acid sequence of SEQ ID NO: 2;
(ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 comprising the amino acid sequences of SEQ ID NOs: 19, 20, and 21, respectively; and a VH comprising the amino acid sequence of SEQ ID NO: 3;
(iii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 comprising the amino acid sequences of SEQ ID NOs: 19, 20, and 21, respectively; and a VH comprising the amino acid sequence of SEQ ID NO: 4;
(iv) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 comprising the amino acid sequences of SEQ ID NOs: 19, 20, and 21, respectively; and a VH comprising the amino acid sequence of SEQ ID NO: 5;
(v) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 comprising the amino acid sequences of SEQ ID NOs: 19, 20, and 21, respectively; and a VH comprising the amino acid sequence of SEQ ID NO: 6;
(vi) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 comprising the amino acid sequences of SEQ ID NOs: 59, 60, and 61, respectively; and a VH comprising the amino acid sequence of SEQ ID NO: 2;
(vii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 comprising the amino acid sequences of SEQ ID NOs: 59, 60, and 61, respectively; and a VH comprising the amino acid sequence of SEQ ID NO: 3;
(viii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 comprising the amino acid sequences of SEQ ID NOs: 59, 60, and 61, respectively; and a VH comprising the amino acid sequence of SEQ ID NO: 4;
(ix) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 comprising the amino acid sequences of SEQ ID NOs: 59, 60, and 61, respectively; and a VH comprising the amino acid sequence of SEQ ID NO: 5;
(x) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 comprising the amino acid sequences of SEQ ID NOs: 59, 60, and 61, respectively; and a VH comprising the amino acid sequence of SEQ ID NO: 6;
(xi) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 comprising the amino acid sequences of SEQ ID NOs: 66, 67, and 68, respectively; and a VH comprising the amino acid sequence of SEQ ID NO: 2;
(xii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 comprising the amino acid sequences of SEQ ID NOs: 66, 67, and 68, respectively; and a VH comprising the amino acid sequence of SEQ ID NO: 3;
(xiii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 comprising the amino acid sequences of SEQ ID NOs: 66, 67, and 68, respectively; and a VH comprising the amino acid sequence of SEQ ID NO: 4;
(xiv) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 comprising the amino acid sequences of SEQ ID NOs: 66, 67, and 68, respectively; and a VH comprising the amino acid sequence of SEQ ID NO: 5;
(xv) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 comprising the amino acid sequences of SEQ ID NOs: 66, 67, and 68, respectively; and a VH comprising the amino acid sequence of SEQ ID NO: 6;
(xvi) a VL comprising the amino acid sequence of SEQ ID NO: 7, and a VH comprising a VH CDR1, VH CDR2, and VH CDR3 comprising the amino acid sequences of SEQ ID NOs: 16, 17, and 18, respectively;
(xvii) a VL comprising the amino acid sequence of SEQ ID NO: 8, and a VH comprising a VH CDR1, VH CDR2, and VH CDR3 comprising the amino acid sequences of SEQ ID NOs: 16, 17, and 18, respectively;
(xviii) a VL comprising the amino acid sequence of SEQ ID NO: 9, and a VH comprising a VH CDR1, VH CDR2, and VH CDR3 comprising the amino acid sequences of SEQ ID NOs: 16, 17, and 18, respectively;
(xix) a VL comprising the amino acid sequence of SEQ ID NO: 10, and a VH comprising a VH CDR1, VH CDR2, and VH CDR3 comprising the amino acid sequences of SEQ ID NOs: 16, 17, and 18, respectively;
(xx) a VL comprising the amino acid sequence of SEQ ID NO: 7, and a VH comprising a VH CDR1, VH CDR2, and VH CDR3 comprising the amino acid sequences of SEQ ID NOs: 56, 57, and 58, respectively;
(xxi) a VL comprising the amino acid sequence of SEQ ID NO: 8, and a VH comprising a VH CDR1, VH CDR2, and VH CDR3 comprising the amino acid sequences of SEQ ID NOs: 56, 57, and 58, respectively;
(xxii) a VL comprising the amino acid sequence of SEQ ID NO: 9, and a VH comprising a VH CDR1, VH CDR2, and VH CDR3 comprising the amino acid sequences of SEQ ID NOs: 56, 57, and 58, respectively;
(xxiii) a VL comprising the amino acid sequence of SEQ ID NO: 10, and a VH comprising a VH CDR1, VH CDR2, and VH CDR3 comprising the amino acid sequences of SEQ ID NOs: 56, 57, and 58, respectively;
(xxiv) a VL comprising the amino acid sequence o

Assignees

• Kolltan Pharmaceuticals Inc
• Celldex Therapeutics Inc

Inventors

• Hadari Yaron
• Mandel-Bausch Elizabeth M
• Carr Francis Joseph
• Jones Timothy David
• Perry Laura Clare Alexandra

Classifications

• A61P43/00

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

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P11/06

  Antiasthmatics · CPC title