IGF-1R specific antibodies useful in the detection and diagnosis of cellular proliferative disorders

• US 8,344,112 B2
• Filed: 07/25/2008
• Issued: 01/01/2013
• Est. Priority Date: 07/31/2007
• Status: Expired due to Fees

• Current Assignee: Pierre Fabre Medicament (Fondation Pierre Fabre), Merck Sharp & Dohme Limited (Merck & Co., Inc.)
• Original Assignee: Merck Sharp & Dohme Limited (Merck & Co., Inc.)
• Inventors: Goetsch, Liliane, Brooks, David, Chastain, Michael, Zhang, Zhi-Qiang, Corvaia, Nathalie
• Primary Examiner(s): Stucker, Jeffrey
• Assistant Examiner(s): WEGERT, SANDRA L
• Application Number:
  US12/670,863
• Publication Number:
  US 20100215573A1
• Time in Patent Office: 1,621 Days
• Field of Search: None
• US Class Current: 530/388.1
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 16/2863 against receptors for growth factors, growth regulators
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: G01N 2333/71 for growth factors; for growth regulators
• CPC Class Codes: G01N 33/574 for cancer

Abstract

The present invention relates to mammalian antibodies, designated 12B1 and antigen-binding portions thereof that specifically bind to insulin-like growth factor I receptor (IGF-IR), preferably human IGF-IR. Also included are chimeric, bispecific, derivatized, single chain antibodies derived from the antibodies disclosed herein. Nucleic acid molecules encoding the mammalian antibodies as well as methods of use thereof are also disclosed. Also included are pharmaceutical compositions comprising these antibodies and methods of using the antibodies and compositions thereof for treatment and diagnosis of pathological hyperproliferative oncogenic disorders associated with expression of IGF-1R.

Claims

1. An isolated antibody or an antigen-binding portion thereof that specifically binds insulin-like growth factor I receptor, comprising a light chain immunoglobulin that comprises three complementarity determining regions comprising the amino acid sequences set forth in SEQ ID NO. 1, 2, and 3, and a heavy chain immunoglobulin that comprises three complementarity determining regions comprising the amino acid sequence set forth in SEQ ID NO. 4, 5 and 6.

2. The antibody or antigen-binding portion according to claim 1, which is an antigen-binding portion wherein said antigen-binding portion is selected from the group consisting of:

a Fab fragment, an F(ab′

)2 fragment and an Fv fragment.

3. The antibody according to claim 1, wherein said light chain comprises the amino acid sequence as set forth in SEQ ID NO:

7 and said heavy chain comprises the amino acid sequence as set forth in SEQ ID NO;

8.

4. The antibody or antigen-binding portion of claim 1 which is an antibody wherein said antibody is an isotype selected from the group consisting of IgM, IgD, IgG, IgA, and IgE.

5. The antibody or antigen-binding portion of claim 1 which is an antibody wherein said antibody is a monoclonal antibody, a humanized antibody or a human antibody.

6. The antibody or antigen-binding portion of claim 1 which is an antibody wherein said antibody is a chimeric antibody.

7. The antibody or antigen-binding portion of claim 1 which is conjugated.

8. The antibody or antigen-binding portion of claim 7 which is conjugated, wherein the antibody or antigen-binding portion is conjugated to a member selected from the group consisting of Lead-212, Bismuth-212, Astatine-211, Iodine-131, Scandium-47, Rhenium-186, Rhenium-188, Yttrium-90, Iodine-123, Iodine-125, Bromine-77, Indium-111, Boron-10, polyethylene glycol, an Actinide and a cytotoxic drug.

9. The antibody or antigen-binding portion of claim 7 which is conjugated, wherein the antibody or antigen-binding portion is conjugated to a member selected from the group consisting of ricin, modified Pseudomonas enterotoxin A, calicheamicin, adriamycin and 5-fluorouracil.

10. The antibody or antigen-binding portion of claim 1 which is bound to insulin-like growth factor I receptor.

11. A method for making the antibody or antigen-binding portion of claim 1 comprising transforming a vector comprising a nucleic acid molecule encoding said light chain immunoglobulin and said heavy chain immunoglobulin into a host cell and culturing the host cell in a medium under conditions favoring expression of the chains.

12. The method of claim 11 further comprising recovering the antibody or antigen-binding portion from the medium.