Anti-CCR5 antibody
View Patent ↗The invention is directed an anti-CCR5 antibody which comprises (i) two light chains, each light chain comprising the expression product of a plasmid designated pVK:HuPRO140-VK (ATCC Deposit Designation PTA-4097), and (ii) two heavy chains, each heavy chain comprising an expression product of either a plasmid designated pVg1:HuPRO140 HG2-VH (ATCC Deposit Designation PTA-4098) or a plasmid designated pVg1:HuPRO140 (mutB+D+I)-VH (ATCC Deposit Designation PTA-4099) or a fragment thereof which binds to CCR5 on the surface of a human cell.
1. An anti-CCR5 antibody fragment comprising an antibody fragment selected from the group consisting of:
(a) a light chain, which light chain comprises the expression product of a plasmid designated pVK:HuPRO140-VK (ATCC Deposit Designation PTA-4097);
(b) a heavy chain, which heavy chain comprises the expression product of either a plasmid designated pVg4:HuPRO140 HG2-VH (ATCC Deposit Designation PTA-4098) or a plasmid designated pVg4:HuPRO140 (mut B+D+I)-VH (ATCC Deposit Designation PTA-4099);
(c) a Fab fragment which comprises (i) two light chains, each light chain comprising the expression product of a plasmid designated pVK:HuPRO140-VK (ATCC Deposit Designation PTA-4097), and (ii) two heavy chains, each heavy chain comprising the expression product of either a plasmid designated pVg4:HuPRO140 HG2-VH (ATCC Deposit Designation PTA-4098) or a plasmid designated pVg4:HuPRO140 (mut B+D+I)-VH (ATCC Deposit Designation PTA-4099); and
(d) a F(ab′) 2 fragment which comprises (i) two light chains, each light chain comprising the expression product of a plasmid designated pVK:HuPRO140-VK (ATCC Deposit Designation PTA-4097), and (ii) two heavy chains, each heavy chain comprising the expression product of either a plasmid designated pVg4:HuPRO140 HG2-VH (ATCC Deposit Designation PTA-4098) or a plasmid designated pVg4:HuPRO140 (mut B+D+I)-VH (ATCC Deposit Designation PTA-4099);
and which antibody fragment binds to CCR5 on the surface of a human cell.
2. The anti-CCR5 antibody fragment of claim 1 , wherein the antibody fragment is the light chain expressed by the plasmid designated pVK:HuPRO140-VK (ATCC Deposit Designation PTA-4097).
3. The anti-CCR5 antibody fragment of claim 1 , wherein the antibody fragment is the heavy chain expressed by the plasmid designated pVg4:HuPRO140 HG2-VH (ATCC Deposit Designation PTA-4098).
4. The anti-CCR5 antibody of claim 1 , wherein the antibody fragment is the heavy chain expressed by the plasmid designated pVg4:HuPRO140 (mut B+D+I)-VH (ATCC Deposit Designation PTA-4099).
5. The anti-CCR5 antibody fragment of claim 1 , wherein the antibody fragment is the Fab fragment of the anti-CCR5 antibody which comprises (i) two light chains, each light chain comprising the expression product of a plasmid designated pVK:HuPRO140-VK (ATCC Deposit Designation PTA-4097), and (ii) two heavy chains, each heavy chain comprising the expression product of either a plasmid designated pVg4:HuPRO140 HG2-VH (ATCC Deposit Designation PTA-4098) or a plasmid designated pVg4:HuPRO140 (mut B+D+I)-VH (ATCC Deposit Designation PTA-4099).
6. The anti-CCR5 antibody fragment of claim 1 , wherein the antibody fragment is the F(ab′) 2 fragment of the anti-CCR5 antibody which comprises (i) two light chains, each light chain comprising the expression product of a plasmid designated pVK:HuPRO140-VK (ATCC Deposit Designation PTA-4097), and (ii) two heavy chains, each heavy chain comprising the expression product of either a plasmid designated pVg4:HuPRO140 HG2-VH (ATCC Deposit Designation PTA-4098) or a plasmid designated pVg4:HuPRO140 (mut B+D+I)-VH (ATCC Deposit Designation PTA-4099).
7. The anti-CCR5 antibody fragment of claim 5 , wherein the heavy chains comprise the expression product of the plasmid designated pVg4:HuPRO140 HG2-VH (ATCC Deposit Designation PTA-4098).
8. The anti-CCR5 antibody fragment of claim 5 , wherein the heavy chains comprise the expression product of the plasmid designated pVg4:HuPRO140 (mut B+D+I)-VH (ATCC Deposit Designation PTA-4099).
9. The anti-CCR5 antibody fragment of claim 6 , wherein the heavy chains comprise the expression product of the plasmid designated pVg4:HuPRO140 HG2-VH (ATCC Deposit Designation PTA-4098).
10. The anti-CCR5 antibody fragment of claim 6 , wherein the heavy chains comprise the expression product of the plasmid designated pVg4:HuPRO140 (mut B+D+I)-VH (ATCC Deposit Designation PTA-4099).
11. An anti-CCR5 antibody fragment comprising (i) a light chain which comprises consecutive amino acids having the sequence set forth in SEQ ID NO:6; or (ii) a heavy chain which comprises consecutive amino acids having the sequence set forth in SEQ ID NO:9 or SEQ ID NO:12.
12. A composition comprising the anti-CCR5 antibody fragment of claim 1 or claim 11 and a carrier, a diluent or an excipient.
13. The composition of claim 12 , wherein the anti-CCR5 antibody fragment has attached thereto a material selected from the group consisting of a radioisotope, a toxin, polyethylene glycol, a cytotoxic agent and a detectable label.
14. A method of inhibiting HIV-1 infection of a CD4+ cell which comprises contacting the CD4+ cell with the anti-CCR5 antibody fragment of claim 1 or claim 11 , in an amount and under conditions such that fusion of HIV-1 or an HIV-1 infected cell to the CD4+ cell is inhibited, thereby inhibiting HIV-1 infection of the CD4+ cell.
15. The method of claim 14 , which further comprises labeling the anti-CCR5 antibody fragment with a detectable marker.
16. The method of claim 15 , wherein the detectable marker is a radioactive or a fluorescent marker.
17. The method of claim 14 , wherein the CD4+ cell expresses CCR5.
18. A method of treating a subject afflicted with HIV-1 which comprises administering to the subject an effective HIV-1 treating dosage amount of the composition of claim 12 , under conditions effective to treat said HIV-1-afflicted subject.
19. The method of claim 18 , wherein the composition is administered to the subject by a method selected from the group consisting of intravenous, intramuscular and subcutaneous means.
20. The method of claim 18 , wherein the composition is administered continuously to said subject or at predetermined periodic intervals.
21. The method of claim 18 , wherein the dosage of said composition ranges from about 0.1 to about 100,000 μg/kg body weight of said subject.
22. The method of claim 18 , wherein the dosage of said composition does not inhibit an endogenous chemokine activity on CCR5 in said subject.
23. A method of preventing a subject from contracting an HIV-1 infection which comprises administering to the subject an effective HIV-1 infection-preventing dosage amount of the composition of claim 12 , under conditions effective to prevent said HIV-1 infection in said subject.
24. The method of claim 23 , wherein the anti-CCR5 antibody fragment is administered to the subject by a method selected from the group consisting of intravenous, intramuscular and subcutaneous means.
25. The method of claim 23 , wherein the anti-CCR5 antibody fragment is administered continuously to said subject or at predetermined periodic intervals.
26. The method of claim 23 , wherein the dosage of said anti-CCR5 antibody fragment ranges from about 0.1 to about 100,000 μg/kg body weight of said subject.
27. The method of claim 23 , wherein the dosage of said anti-CCR5 antibody fragment does not inhibit an endogenous chemokine activity on CCR5 in said subject.