Method of transplanting cells by contacting donor cells with B7-1-and B7-2-specific immunoglobulins

• US 6,984,383 B1
• Filed: 07/27/2000
• Issued: 01/10/2006
• Est. Priority Date: 02/12/1999
• Status: Expired due to Fees

• Current Assignee: Genetics Institute LLC (Pfizer Inc.)
• Original Assignee: Genetics Institute LLC (Pfizer Inc.)
• Inventors: Vasquez, Maximiliano, Collins, Mary, O'Hara, Denise, Veldman, Geertruida M., Goldman, Samuel, Rup, Bonita, Knight, Andrea, Carreno, Beatriz, Gray, Gary S., Co, Man Sung, Celniker, Abbie Cheryl
• Primary Examiner(s): Gambel, Phillip
• Application Number:
  US09/626,731
• Time in Patent Office: 1,993 Days
• Field of Search: 424/130.1, 424/133.1, 424/143.1, 424/173.1, 424/577, 530/387.1, 530/388.2, 530/388.73
• US Class Current: 424/153.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: C07K 16/2827 against B7 molecules, e.g. CD80, CD86
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/52 Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

Abstract

The invention relates to a humanized anti-B7-2 antibody that comprises a variable region of nonhuman origin and at least a portion of an immunoglobulin of human origin. The invention also pertains to methods of treatment for various autoimmune diseases, transplant rejection, inflammatory disorders and infectious diseases by administering humanized anti-B7-2 and/or anti-B7-1 antibodies.

Claims

1. A method for transplanting cells to a patient in need thereof, comprising:

a) obtaining cells from a donor,

b) obtaining recipient cells from the patient;

c) contacting the donor cells with an immunoglobulin specific to B7-1 and an immunoglobulin specific to B7-2, wherein the immunoglobulin specific to B7-2 has a binding affinity of at least about 10⁷ M<sup>−

1</sup>, and wherein said immunoglobulin comprises an antigen binding region of non-human origin and at least a portion of an immunoglobulin of human origin, further wherein the antigen binding region of non-human origin comprises at least one framework region containing a substitution of at least one amino acid to a corresponding amino acid in the III2R heavy chain framework region or the H2F light chain framework region;

d) combining b) and c) to form a mixture, and

e) introducing the mixture of step d) to the patient.

2. The method of claim 1, wherein the cells from the donor are derived from bone marrow or blood.

3. The method of claim 2, wherein the recipient cell is a lymphocyte.

4. The method of claim 3, wherein the immunoglobulin specific to B7-1, and the immunoglobulin specific to B7-2 are in contact with the donor cells for a period of time between about 12 hours and 48 hours.

5. The method of claim 4, wherein the period of time is about 36 hours.

6. The method of claim 1, wherein the patient has a disease that is selected from the group consisting of:

a proliferative disease, anemia and myeloid dysplasia syndrome.

7. The method of claim 6, wherein the proliferative disease is selected from the group consisting of:

leukemia, lymphoma and cancer.

8. The method of claim 6, wherein the anemia is selected from the group consisting of:

sickle-cell anemia, thalassemia and aplastic anemia.

9. The method of claim 1, wherein the immunoglobulin specific to B7-1 and the immunoglobulin specific to B7-2 are humanized.

10. The method of claim 1, wherein the immunoglobulin specific to B7-1 and the immunoglobulin specific to B7-2 are in contact with the donor cells for a period of time between about 1 hour and 48 hours.

11. The method of claim 1, wherein the immunoglobulin specific to B7-2 can compete with the murine antibody 3D1 (SEQ ID NOS:

2 and

     4) for binding to B7-2.

12. The method of claim 1, wherein the immunoglobulin specific to B7-2 is derived from the cell line deposited with the ATCC, Accession No. CRL-12524.

13. A method for transplanting cells to a patient in need thereof, comprising:

a) obtaining cells from a donor,

b) obtaining a tissue, an organ, or recipient cells from the patient,

c) contacting the donor cells with an immunoglobulin specific to B7-1 and an immunoglobulin specific to B7-2, wherein the immunoglobulin specific to B7-2 has a binding affinity of at least about 10⁷ M<sup>−

1</sup>, and wherein said immunoglobulin comprises an antigen binding region of non-human origin and at least a portion of an immunoglobulin of human origin, further wherein the antigen binding region of non-human origin comprises at least one framework region containing a substitution of at least one amino acid to a corresponding amino acid in the III2R heavy chain framework region or the H2F light chain framework region;

d) combining b) and c) to form a mixture, and

e) introducing the mixture of step d) to the patient.

14. The method of claim 13, wherein the cells derived from the donor are derived from bone marrow, stem cells or immature blood cells.

15. The method of claim 13, wherein the immunoglobulin specific to B7-1 and the immunoglobulin specific to B7-2 are in contact with the donor cells for a period of time between about 1 hour and 48 hours.

16. The method of claim 13, wherein the immunoglobulin specific to B7-1 and the immunoglobulin specific to B7-2 are humanized.

17. The method of claim 13, wherein the immunoglobulin specific to B7-2 can compete with the murine antibody 3D1 (SEQ ID NOS:

2 and

     4) for binding to B7-2.

18. The method of claim 13, wherein the immunoglobulin specific to B7-2 is derived from the cell line deposited with the ATCC, Accession No. CRL-12524.