IP Library Granted Patent US 7,528,235
Granted Patent B2
US 7,528,235 · App. 10/350,555 · Granted May 5, 2009

Multi-functional antibodies

Assignee: The Regents of the Univarsity of California
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Quick Facts
Patent No.
US 7,528,235
App. No.
10/350,555
Granted
May 5, 2009
Kind
B2
Abstract

The present invention provides a mutant antibody comprising a reactive site not present in the wild-type of the antibody and a antigen recognition domain that specifically binds to a metal chelate, wherein the reactive site is in a position proximate to or within the antigen recognition domain.

Claims (45)

1. An isolated antibody comprising:

i) A light chain comprising:

a) A first CDR having the sequence of SEQ ID NO: 2;

b) A second CDR having a sequence selected from the group consisting of:

i) SEQ ID NO: 3; and

ii) SEQ ID NO: 3 containing a cysteine substitution wherein position 2 is substituted by a cysteine;

c) A third CDR having the sequence of SEQ. ID. NO: 4;

ii) A heavy chain comprising:

a) A first CDR having the sequence of SEQ ID NO: 6;

b) A second CDR having a sequence selected from the group consisting of:

i) SEQ ID NO: 7;

ii) SEQ ID NO: 7 containing a cysteine substitution wherein position 5 has been substituted by a cysteine;

iii) SEQ ID NO: 7 containing a cysteine substitution wherein position 6 has been substituted by a cysteine; and

iv) SEQ ID NO: 7 containing a cysteine substitution wherein

position 7 has been substituted by a cysteine;

c) A third CDR having the sequence SEQ ID NO: 8;

wherein said antibody comprises at least one of said cysteine substitutions, and wherein said antibody binds substituted or unsubstituted 1,4,7,10-tetraazacyclododecane-N,N′,N″,N″-tetraacetic acid (DOTA).

2. The antibody of claim 1 wherein said cysteine substitution interacts with a reactive functional group on said DOTA of complementary reactivity to said cysteine substitution of said antibody and said reactive functional group is a member selected from carboxyl groups, hydroxyl groups, haloalkyl groups, dienophile groups, aldehyde groups, ketone groups, sulfonyl halide groups, thiol groups, amine groups, sulfhydryl groups, alkene groups and epoxide groups.

3. The antibody according to claim 1 further comprising said DOTA bound to said antibody, wherein said DOTA comprises a reactive functional group of complementary reactivity to a thiol group of said cysteine substitution of said antibody.

4. The antibody according to claim 3 , further comprising a covalent bond between a sulfur atom of said thiol group of said antibody and said reactive functional group of said DOTA.

5. The antibody of claim 1 , further comprising a targeting moiety.

6. The antibody according to claim 5 , wherein said targeting moiety binds specifically to a cell surface protein.

7. The antibody according to claim 5 , wherein the targeting moiety is covalently attached to said antibody.

8. The antibody according to claim 6 , wherein the targeting moiety is a second antibody.

9. The antibody according to claim 6 , wherein said cell surface protein is specific to a cancer cell.

10. An isolated antibody having a variable light chain sequence of SEQ. ID. NO: 23 and a variable heavy chain sequence of SEQ. ID. NO: 5.

11. An isolated antibody having a variable light chain sequence of SEQ. ID. NO: 1 and a variable heavy chain sequence selected from the group consisting of:

i.) SEQ. ID. NO: 12;

ii.) SEQ. ID. NO: 13;

iii.) SEQ. ID. NO: 14;

iv.) SEQ. ID. NO: 37;

v.) SEQ. ID. NO: 38; and

vi.) SEQ. ID. NO: 39.

12. A composition having the structure:

(Ab) n′ -L-T

wherein,

n′is an integer from 1-10;

Ab represents an antibody according to claim 1 ;

L is a chemical bond or linking group that may contain one or more functional groups; and

T is a targeting moiety.

13. The composition of claim 12 ,wherein said targeting moiety is an antibody that binds specifically to a cell surface antigen.

14. A pharmaceutical composition comprising the composition of claim 12 , and a pharmaceutically acceptable carrier.

15. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.

16. A pharmaceutical composition comprising the antibody of claim 3 , and a pharmaceutically acceptable carrier.

17. A pharmaceutical composition comprising the antibody of claim 4 and a pharmaceutically acceptable carrier.

Assignments (3)
CONFIRMATORY LICENSE Recorded Mar 5, 2010
From: UNIVERSITY OF CALIFORNIA
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 024038/0722 →
CONFIRMATORY LICENSE Recorded Apr 16, 2008
From: UNIVERSITY OF CALIFORNIA
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 020812/0534 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 8, 2003
From: MEARES, CLAUDE F.; CORNEILLIE, TODD M.
To: REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE
Reel/Frame 013783/0204 →
Continuity (1)
Related Publication 20040146934A1 · Jul 29, 2004