Claims for Patent: 10,035,848

Summary for Patent: 10,035,848

Title:	Antibody targeting cell surface deposited complement protein C3d and use thereof
Abstract:	An anti-C3d antibody or antibody fragment; method for use thereof to kill cancer cells; and related methods and compositions.
Inventor(s):	Wiestner; Adrian U. (Bethesda, MD), Skarzynski; Martin W. (North Bethesda, MD), Lindorfer; Margaret A. (Keswick, VA), Taylor; Ronald P. (Keswick, VA), Rader; Christoph (Jupiter, FL), Vire; Berengere (Le Cres, FR)
Assignee:	The United States of America, as represented by the Secretary, Department of Health and Human Services (Washington, DC) University of Virginia Patent Foundation (Charlottesville, VA)
Application Number:	15/110,577
Patent Claims:	1. An anti-C3d antibody or antibody fragment comprising a heavy chain variable region comprising SEQ ID NO: 1 as heavy chain complementary determining region-1 (CDRH1); SEQ ID NO: 2 as heavy chain complementary determining region-2 (CDRH2); and SEQ ID NO: 3 or 4 as heavy chain complementary determining region-3 (CDRH3); and a light chain variable region comprising SEQ ID NO: 5 as light chain complementary determining region-1 (CDRL1); SEQ ID NO: 6 as light chain complementary determining region-2 (CDRL2); and SEQ ID NO: 7 as light chain complementary determining region-3 (CDRL3). 2. An anti-C3d antibody or antibody fragment comprising a heavy chain variable region comprising SEQ ID NO: 1 as heavy chain complementary determining region-1 (CDRH1); SEQ ID NO: 2 as heavy chain complementary determining region-2 (CDRH2); and SEQ ID NO: 3 as heavy chain complementary determining region-3 (CDRH3); and a light chain variable region comprising SEQ ID NO: 5 as light chain complementary determining region-1 (CDRL1); SEQ ID NO: 6 as light chain complementary determining region-2 (CDRL2); and SEQ ID NO: 7 as light chain complementary determining region-3 (CDRL3). 3. The anti-C3d antibody or antibody fragment of claim 1, wherein the heavy chain comprises SEQ ID NO: 8 and the light chain comprises SEQ ID NO: 9. 4. An anti-C3d antibody or antibody fragment comprising a heavy chain variable region comprising SEQ ID NO: 1 as heavy chain complementary determining region-1 (CDRH1); SEQ ID NO: 2 as heavy chain complementary determining region-2 (CDRH2); and SEQ ID NO: 4 as heavy chain complementary determining region-3 (CDRH3); and a light chain variable region comprising SEQ ID NO: 5 as light chain complementary determining region-1 (CDRL1); SEQ ID NO: 6 as light chain complementary determining region-2 (CDRL2); and SEQ ID NO: 7 as light chain complementary determining region-3 (CDRL3). 5. The anti-C3d antibody or antibody fragment of claim 1, wherein the heavy chain comprises SEQ ID NO: 10 and the light chain comprises SEQ ID NO: 11. 6. The anti-C3d antibody or antibody fragment of claim 1, wherein the antibody binds to an epitope comprising SEQ ID NO: 16 or an epitope within SEQ ID NO: 16. 7. The antibody or antibody fragment of claim 1, wherein the antibody or antibody fragment is selected from the group consisting of IgA1, IgA2, IgD, IgE, IgG1, IgG2, IgG3, IgG4, IgM, scFv, IgG.DELTA.CH.sub.2, F(ab')2, scFv2CH3, F(ab), scFv4, scFv3, scFv2, dsFv, Fv, scFv-Fc, (scFv)2, a diabody, a T-body, a multispecific antibody, and a multivalent antibody. 8. The antibody or antibody fragment of claim 1, wherein the antibody or antibody fragment is conjugated to another molecule. 9. The antibody of claim 8, wherein the antibody or antibody fragment conjugated to a transmembrane region and an intracellular T-cell receptor (TCR) signaling domain to provide a T-body. 10. The antibody of claim 8, wherein the anti-C3d antibody or antibody fragment is conjugated to a label. 11. The antibody of claim 8, wherein the anti-C3d antibody or antibody fragment is conjugated to a cytotoxic agent or a therapeutic radioisotope. 12. A method of killing a cancer cell having C3d complement protein on the surface thereof in a subject, the method comprising administering to the subject an anti-C3d antibody or antibody fragment of claim 1. 13. The method of claim 12, further comprising inducing the formation of C3d complement protein on the surface of the cancer cell by contacting the cell with an antibody or antibody fragment to a cell-surface protein other than C3d. 14. The method of claim 13, wherein the anti-C3d antibody is a multi-specific antibody that is immunospecific for C3d and a cell-surface protein other than C3d, and contacting the cell with an antibody or antibody fragment to a cell-surface protein other than C3d is accomplished by administering the multi-specific antibody. 15. A pharmaceutical composition comprising the antibody or antibody fragment of claim 1. 16. A nucleic acid encoding the antibody or antibody fragment of claim 1, optionally in a vector. 17. A method of preparing an antibody or antibody fragment of claim 1, the method comprising expressing a nucleic acid encoding the antibody or antibody fragment in a cell. 18. A cell comprising the nucleic acid of claim 16. 19. The method of claim 13, wherein the antibody or antibody fragment to a cell-surface protein other than C3d is administered simultaneously with the administration of the anti-C3d antibody or antibody fragment. 20. The method of claim 13, wherein the antibody or antibody fragment to a cell-surface protein other than C3d is administered sequentially in any order with the administration of the anti-C3d antibody or antibody fragment. 21. The method of claim 13, wherein the antibody or antibody fragment to a cell surface protein other than C3d is an anti-CD20 antibody or antibody fragment. 22. The method of claim 21, wherein the anti-CD20 antibody or antibody fragment is rituximab, ofatumumab, ocrelizumab, veltuzumab, obinutuzumab, PRO131921, or ocaratuzumab. 23. The method of claim 21, wherein the cancer cell is a B-cell expressing CD20. 24. A method of killing a cancer cell having C3d complement protein on the surface thereof in a subject, the method comprising administering to the subject an anti-C3d antibody or antibody fragment of claim 2. 25. A method of killing a cancer cell having C3d complement protein on the surface thereof in a subject, the method comprising administering to the subject an anti-C3d antibody or antibody fragment of claim 4.

Details for Patent 10,035,848

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2034-01-08
Novartis Pharmaceuticals Corporation	ARZERRA	ofatumumab	Injection	125326	10/26/2009		2034-01-08
Novartis Pharmaceuticals Corporation	ARZERRA	ofatumumab	Injection	125326	04/01/2011		2034-01-08
Novartis Pharmaceuticals Corporation	KESIMPTA	ofatumumab	Injection	125326	08/20/2020		2034-01-08
Genentech, Inc.	GAZYVA	obinutuzumab	Injection	125486	11/01/2013		2034-01-08
Genentech, Inc.	OCREVUS	ocrelizumab	Injection	761053	03/28/2017		2034-01-08
Genentech, Inc.	RITUXAN HYCELA	rituximab and hyaluronidase human	Injection	761064	06/22/2017		2034-01-08