Neutralizing human anti-IGFR antibody
AssigneeSchering Corporation
InventorsYan Wang, Robert Greenberg, Leonard Presta, Jonathan A. Pachter, Judith Hailey, Peter Brams, Denise Williams, Mohan Srinivasan, Diane Feingersh
Life of this patent
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Abstract
The present invention includes fully human, neutralizing, monoclonal antibodies against human Insulin-like Growth Factor Receptor-I (IGFR1). The antibodies are useful for treating or preventing cancer in a subject. Also included are methods of using and producing the antibodies of the invention.
Claims20
A binding composition that specifically binds to IGFR1 comprising a member selected from the group consisting of:
- a) a light chain amino acid sequence which comprises CDR-L1 defined by SEQ ID. NO:
- 8, CDR-L2 defined by SEQ ID NO:
- 9 and CDR-L3 defined by SEQ ID NO:
- 10;
- b) a light chain amino acid sequence which comprises CDR-L1 defined by SEQ ID NO:
- 31, CDR-L2 defined by SEQ ID NO:
- 32 and CDR-L3 defined by SEQ ID NO:
- 33;
- c) a heavy chain amino acid sequence which comprises CDR-H1 defined by SEQ ID NO:
- 14 or SEQ ID. NO:
- 17, CDR-H2 defined by SEQ ID NO:
- 15 and CDR-H3 defined by SEQ ID NO:
- 16;
- and
- d) a heavy chain amino acid sequence which comprises CDR-H1 defined by SEQ ID NO:
- 37 or SEQ ID NO:
- 70, CDR-H2 defined by SEQ ID NO:
- 38 and CDR-H3 defined by SEQ ID NO:
- 39.
A binding composition that specifically binds to IGFR1 comprising a member selected from the group consisting of:
- (a) a light chain variable region comprising amino acids 20-128 of SEQ ID NO:
- 2 and a heavy chain variable region comprising amino acids 20-137 of SEQ ID NO:
- 4;
- (b) a light chain variable region comprising amino acids 21-130 of SEQ ID NO:
- 25 and a heavy chain variable region comprising amino acids 20-140 of SEQ ID NO:
- 27;
- (c) a light variable region comprising amino acids 20-128 of SEQ ID NO:
- 72 and a heavy chain variable region comprising amino acids 20-137 of SEQ ID NO:
- 45;
- (d) a light variable region comprising amino acids 20-128 of SEQ ID NO:
- 74 and a heavy chain variable region comprising amino acids 20-137 of SEQ ID NO:
- 45;
- (e) a light variable region comprising amino acids 20-128 of SEQ ID NO:
- 76 and a heavy chain variable region comprising amino acids 20-137 of SEQ ID NO:
- 45;
- (f) a light variable region comprising amino acids 20-128 of SEQ ID NO:
- 78 and a heavy chain variable region comprising amino acids 20-137 of SEQ ID NO:
- 45;
- (g) a light variable region comprising amino acids 20-128 of SEQ ID NO:
- 72 and a heavy chain variable region comprising amino acids 20-137 of SEQ ID NO:
- 112;
- (h) a light variable region comprising amino acids 20-128 of SEQ ID NO:
- 74 and a heavy chain variable region comprising amino acids 20-137 of SEQ ID NO:
- 112;
- (i) a light variable region comprising amino acids 20-128 of SEQ ID NO:
- 76 and a heavy chain variable region comprising amino acids 20-137 of SEQ ID NO:
- 112;
- and
- (j) a light variable region comprising amino acids 20-128 of SEQ ID NO:
- 78 and a heavy chain variable region comprising amino acids 20-137 of SEQ ID NO:
- 112.
An isolated nucleic acid encoding a polypeptide selected from the group consisting of:
- (a) amino acids 20-128 of SEQ ID NO:
- 2;
- (b) amino acids 21-130 of SEQ ID NO:
- 25;
- (c) amino acids 20-128 of SEQ ID NO:
- 72;
- (d) amino acids 20-128 of SEQ ID NO:
- 74;
- (e) amino acids 20-137 of SEQ ID NO:
- 4;
- (f) amino acids 20-140 of SEQ ID NO:
- 27;
- (g) amino acids 20-137 of SEQ ID NO:
- 45;
- (h) amino acids 20-137 of SEQ ID NO:
- 112;
- (i) amino acids 20-128 of SEQ ID NO:
- 76;
- and
- (j) amino acids 20-128 of SEQ ID NO:
- 78.
A method for treating or preventing a medical condition in a subject, which medical condition is mediated by elevated expression or activity of Insulin-like Growth Factor Receptor-I, comprising administering a binding composition that specifically binds to IGFR1 comprising a member selected from the group consisting of:
- (a) a light chain amino acid sequence which comprises CDR-L1 defined by SEQ ID NO:
- 8, CDR-L2 defined by SEQ ID NO:
- 9 and CDR-L3 defined by SEQ ID NO:
- 10;
- (b) a light chain amino acid sequence which comprises CDR-L1 defined by SEQ ID NO:
- 31, CDR-L2 defined by SEQ ID NO:
- 32 and CDR-L3 defined by SEQ ID NO:
- 33;
- (c) a heavy chain amino acid sequence which comprises CDR-H1 defined by SEQ ID NO:
- 14 or SEQ ID NO:
- 17, CDR-H2 defined by SEQ ID NO:
- 15 and CDR-H3 defined by SEQ ID NO:
- 16;
- and
- (d) a heavy chain amino acid sequence which comprises CDR-H1 defined by SEQ ID NO:
- 37 or SEQ ID NO:
- 70, CDR-H2 defined by SEQ ID NO:
- 38 and CDR-H3 defined by SEQ ID NO:
- 39;
- to the subject.
A method for producing a fully human, monoclonal antibody which specifically binds to IGFR1 comprising the steps of:
- (i) immunizing a transgenic non-human animal having a genome comprising a human heavy chain transgene and a human light chain transgene with an IGFR1 antigenic polypeptide, such that the antibody is produced by a B cell of the animal;
- (ii) isolating said B cell of the animal;
- (iii) fusing the B cell with a myeloma cell to form an immortal hybridoma cell that secretes said antibody;
- and
- (iv) isolating the antibody from the hybridoma cell.
A binding composition which specifically binds to human IGFR1 comprising a property selected from the group consisting of:
- (a) Binds to IGFR1 with a Kd of about 86×10−11 or less;
- (b) Has an off rate (Koff) for IGFR1 of about 6.50×10−5 or smaller;
- (c) Has an on rate (Kon) for IGFR1 of about 0.7×105 or greater;
- (d) Competes with IGF1 for binding to IGFR1;
- (e) Inhibits autophosphorylation of IGFR1;
- and
- (f) Inhibits anchorage-independent growth of a cell expressing IGFR1.
Dependencies are inferred from the claim text.