Claims for Patent: 7,981,416

Summary for Patent: 7,981,416

Title:	Humanized immunomodulatory monoclonal antibodies for the treatment of immunodeficiency
Abstract:	The present invention provides to a humanized monoclonal antibody having immunostimulatory effects. This antibody binds specifically to B lymphoblastoid cells, induces proliferation and activation of peripheral blood lymphocytes, particularly T cells, and is capable of eliciting an anti-tumor effect upon administration to subjects suffering from an immune deficiency.
Inventor(s):	Hardy; Britta (Tel Aviv, IL), Jones; Steven Tarran (Radlett, GB), Klapper; Leah (Givataim, IL)
Assignee:	CureTech Ltd. (Yavne, IL) Mor-Research Applications Ltd. (Petach Tikva, IL)
Application Number:	12/406,492
Patent Claims:	1. A method of inducing proliferative activity of lymphocytes, particularly CD4+ T cells, comprising administering to an individual in need thereof and having an immune deficiency, a pharmaceutical composition comprising an effective amount of a humanized monoclonal antibody comprising the complementarity determining regions (CDRs) of murine monoclonal antibody BAT-1 (mBAT-1) and the framework regions (FRs) from an acceptor human immunoglobulin, or modified therefrom, wherein the humanized antibody retains the activity of mBAT-1 monoclonal antibody and comprises: a light chain variable region selected from the group consisting of: BATRKA (SEQ ID NO: 15), BATRKB (SEQ ID NO: 16), BATRKC (SEQ ID NO: 17), and BATRKD (SEQ ID NO: 18), and a heavy chain variable region selected from the group consisting of: BATRHA (SEQ ID NO: 20), BATRHB (SEQ ID NO: 21), BATRHC (SEQ ID NO: 22), BATRHD (SEQ ID NO: 23) and BATRHE (SEQ ID NO: 24). 2. The method of claim 1, wherein the variable regions are selected from the group consisting of: BATRHA/BATRKA (SEQ ID NO: 20/SEQ ID NO: 15), BATRHB/BATRKA (SEQ ID NO: 21/SEQ ID NO: 15), BATRHB/BATRKB (SEQ ID NO: 21/SEQ ID NO: 16), BATRHC/BATRKB (SEQ ID NO: 22/SEQ ID NO: 16), BATRHB/BATRKD (SEQ ID NO: 21/SEQ ID NO: 18), and BATRHC/BATRKD (SEQ ID NO: 22/SEQ ID NO: 18). 3. The method of claim 1, wherein the individual has a blood count that shows a decrease in lymphocytes, particularly CD4+ T cells. 4. The method of claim 3, wherein the individual is suffering from a genetic or an acquired immune deficiency, is in the early stages of HIV infection or has AIDS (Acquired Immune Deficiency Syndrome). 5. A method of inducing cytolytic activity of lymphocytes, particularly of CD4+ T cells, comprising administering to an individual in need thereof and having an immune deficiency, a pharmaceutical composition comprising an effective amount of a humanized monoclonal antibody comprising the complementarity determining regions (CDRs) of murine monoclonal antibody BAT-1 (mBAT-1) and the framework regions (FRs) from an acceptor human immunoglobulin, or modified therefrom, wherein the humanized antibody retains the activity of mBAT-1 monoclonal antibody and comprises: a light chain variable region selected from the group consisting of: BATRKA (SEQ ID NO: 15), BATRKB (SEQ ID NO: 16), BATRKC (SEQ ID NO: 17), and BATRKD (SEQ ID NO: 18), and a heavy chain variable region selected from the group consisting of: BATRHA (SEQ ID NO: 20), BATRHB (SEQ ID NO: 21), BATRHC (SEQ ID NO: 22), BATRHD (SEQ ID NO: 23) and BATRHE (SEQ ID NO: 24). 6. The method of claim 5, wherein the variable regions are selected from the group consisting of: BATRHA/BATRKA (SEQ ID NO: 20/SEQ ID NO: 15), BATRHB/BATRKA (SEQ ID NO: 21/SEQ ID NO: 15), BATRHB/BATRKB (SEQ ID NO: 21/SEQ ID NO: 16), BATRHC/BATRKB (SEQ ID NO: 22/SEQ ID NO: 16), BATRHB/BATRKD (SEQ ID NO: 21/SEQ ID NO: 18), and BATRHC/BATRKD (SEQ ID NO: 22/SEQ ID NO: 18). 7. The method of claim 5, wherein the individual has a blood count that shows a decrease in lymphocytes, particularly CD4+ T cells. 8. The method of claim 7, wherein the individual is suffering from a genetic or an acquired immune deficiency, is in the early stages of HIV infection or has AIDS (Acquired Immune Deficiency Syndrome). 9. A method of inducing stimulatory activity of lymphocytes, particularly CD4+ T cells, comprising administering to an individual in need thereof and having an immune deficiency, a pharmaceutical composition comprising an effective amount of a humanized monoclonal antibody comprising the at least one complementarity determining region (CDR) of murine monoclonal antibody BAT-1 (mBAT-1) and a framework region (FR) from an acceptor human immunoglobulin, or modified therefrom, wherein the humanized antibody retains the activity of mBAT-1 monoclonal antibody and comprises: a light chain variable region selected from the group consisting of: BATRKA (SEQ ID NO: 15), BATRKB (SEQ ID NO: 16), BATRKC (SEQ ID NO: 17), and BATRKD (SEQ ID NO: 18), and a heavy chain variable region selected from the group consisting of: BATRHA (SEQ ID NO: 20), BATRHB (SEQ ID NO: 21), BATRHC (SEQ ID NO: 22), BATRHD (SEQ ID NO: 23) and BATRHE (SEQ ID NO: 24). 10. The method of claim 9, wherein the variable regions are selected from the group consisting of: BATRHA/BATRKA (SEQ ID NO: 20/SEQ ID NO: 15), BATRHB/BATRKA (SEQ ID NO: 21/SEQ ID NO: 15), BATRHB/BATRKB (SEQ ID NO: 21/SEQ ID NO: 16), BATRHC/BATRKB (SEQ ID NO: 22/SEQ ID NO: 16), BATRHB/BATRKD (SEQ ID NO: 21/SEQ ID NO: 18), and BATRHC/BATRKD (SEQ ID NO: 22/SEQ ID NO: 18). 11. The method of claim 9, wherein the individual has a blood count that shows a decrease in lymphocytes, particularly CD4+ T cells. 12. The method of claim 11, wherein the individual is suffering from a genetic or an acquired immune deficiency, is in the early stages of HIV infection or has AIDS (Acquired Immune Deficiency Syndrome). 13. A method of increasing the survival of activated CD4+ T cells comprising administering to an individual in need thereof and having an immune deficiency, a pharmaceutical composition comprising an effective amount of a humanized monoclonal antibody comprising the complementarity determining regions (CDRs) of murine monoclonal antibody BAT-1 (mBAT-1) and the framework regions (FRs) from an acceptor human immunoglobulin, or modified therefrom, wherein the humanized antibody retains the activity of mBAT-1 monoclonal antibody and comprises: a light chain variable region selected from the group consisting of: BATRKA (SEQ ID NO: 15), BATRKB (SEQ ID NO: 16), BATRKC (SEQ ID NO: 17), and BATRKD (SEQ ID NO: 18), and a heavy chain variable region selected from the group consisting of: BATRHA (SEQ ID NO: 20), BATRHB (SEQ ID NO: 21), BATRHC (SEQ ID NO: 22), BATRHD (SEQ ID NO: 23) and BATRHE (SEQ ID NO: 24). 14. The method of claim 13, wherein the variable regions are selected from the group consisting of: BATRHA/BATRKA (SEQ ID NO: 20/SEQ ID NO: 15), BATRHB/BATRKA (SEQ ID NO: 21/SEQ ID NO: 15), BATRHB/BATRKB (SEQ ID NO: 21/SEQ ID NO: 16), BATRHC/BATRKB (SEQ ID NO: 22/SEQ ID NO: 16), BATRHB/BATRKD (SEQ ID NO: 21/SEQ ID NO: 18), and BATRHC/BATRKD (SEQ ID NO: 22/SEQ ID NO: 18). 15. The method of claim 13, wherein the individual has a blood count that shows a decrease in lymphocytes, particularly CD4+ T cells. 16. The method of claim 15, wherein the individual is suffering from a genetic or an acquired immune deficiency, is in the early stages of HIV infection or has AIDS (Acquired Immune Deficiency Syndrome). 17. A method of increasing the survival of activated CD4+ T cells comprising contacting the activated T cells with a pharmaceutical composition comprising an effective amount of a humanized monoclonal antibody comprising the complementarity determining regions (CDRs) of murine monoclonal antibody BAT-1 (mBAT-1) and the framework regions (FRs) from an acceptor human immunoglobulin, or modified therefrom, wherein the humanized antibody retains the activity of mBAT-1 monoclonal antibody and comprises: a light chain variable region selected from the group consisting of: BATRKA (SEQ ID NO: 15), BATRKB (SEQ ID NO: 16), BATRKC (SEQ ID NO: 17), and BATRKD (SEQ ID NO: 18), and a heavy chain variable region selected from the group consisting of: BATRHA (SEQ ID NO: 20), BATRHB (SEQ ID NO: 21), BATRHC (SEQ ID NO: 22), BATRHD (SEQ ID NO: 23) and BATRHE (SEQ ID NO: 24). 18. The method of claim 17, wherein the pharmaceutical composition is administered to an individual that has an immune deficiency and a blood count that shows a decrease in lymphocytes, particularly in CD4+ T cells. 19. The method of claim 18, wherein the individual is suffering from a genetic or an acquired immune deficiency, is in the early stages of HIV infection or has AIDS (Acquired Immune Deficiency Syndrome). 20. The method of claim 17, wherein the variable regions are selected from the group consisting of: BATRHA/BATRKA (SEQ ID NO: 20/SEQ ID NO: 15), BATRHB/BATRKA (SEQ ID NO: 21/SEQ ID NO: 15), BATRHB/BATRKB (SEQ ID NO: 21/SEQ ID NO: 16), BATRHC/BATRKB (SEQ ID NO: 22/SEQ ID NO: 16), BATRHB/BATRKD (SEQ ID NO: 21/SEQ ID NO: 18), and BATRHC/BATRKD (SEQ ID NO: 22/SEQ ID NO: 18).

Details for Patent 7,981,416

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Emergent Biosolutions Canada Inc.	BAT	botulism antitoxin heptavalent (a, b, c, d, e, f, g) - (equine)	Solution	125462	03/22/2013		2022-05-23