Light chain variable regions

Patent metadata

Field	Value
Publication number	US-11033634-B2
Application number	US-201916706174-A
Country	US
Kind code	B2
Filing date	Dec 6, 2019
Priority date	Feb 24, 2012
Publication date	Jun 15, 2021
Grant date	Jun 15, 2021

Abstract

Novel modulators, including antibodies and derivatives thereof, and methods of using such modulators to treat proliferative disorders are provided.

First claim

The invention claimed is:

1. A polypeptide comprising a set of three non-contiguous sequences of amino acids, wherein the amino acids of the set of three non-contiguous sequences are:
(1) TASSSVSSSY (SEQ ID NO: 427);
(2) STSNLAS (SEQ ID NO: 428), wherein the serine residue at position 1 of SEQ ID NO: 428 is optionally substituted by another amino acid and the asparagine residue at position 4 of SEQ ID NO: 428 is optionally substituted by another amino acid; and
(3) HQX 1 X 2 RSPX 3 TFGX 4 GTKLX 5 X 6 X 7 (SEQ ID NO: 429), wherein X 1 is F or Y; X 2 is H or N; X 3 is L or F; X 4 is A or S; X 5 is E or K; X 6 is L or I; and X 7 is K or R.

2. The polypeptide of claim 1 , wherein the amino acid at position 1 of SEQ ID NO: 428 is a charged amino acid.

3. The polypeptide of claim 1 , wherein the amino acid at position 1 of SEQ ID NO: 428 is selected from the group consisting of lysine, arginine, histidine, aspartic acid, and glutamic acid.

4. The polypeptide of claim 1 , wherein the amino acid at position 1 of SEQ ID NO: 428 is arginine.

5. The humanized light chain of claim 1 , wherein the amino acid at position 4 of SEQ ID NO: 428 is a charged amino acid.

6. The polypeptide of claim 1 , wherein the amino acid at position 4 of SEQ ID NO: 428 is selected from the group consisting of lysine, arginine, histidine, aspartic acid, and glutamic acid.

7. The polypeptide of claim 1 , wherein the amino acid at position 4 of SEQ ID NO: 428 is arginine.

8. A humanized light chain comprising a light chain variable region having three complementarity determining regions (CDRs) derived from a donor sequence, wherein the three CDRs comprise:
(1) TASSSVSSSY (SEQ ID NO: 427);
(2) STSNLAS (SEQ ID NO: 428), wherein the serine residue at position 1 of SEQ ID NO: 428 is optionally substituted by another amino acid and the asparagine residue at position 4 of SEQ ID NO: 428 is optionally substituted by another amino acid; and
(3) HQX 1 X 2 RSPX 3 T (SEQ ID NO: 430), wherein X 1 is F or Y; X 2 is H or N; and X 3 is L or F.

9. The humanized light chain of claim 8 , wherein the light chain variable region comprises four VK framework regions, wherein each of the VK framework regions are derived from a human framework sequence.

10. The humanized light chain of claim 9 , wherein the VK framework regions comprise a second non-contiguous amino acid sequence comprising:
EIVLTQSPGTLSLSPGERATLSC (FR1) (SEQ ID NO: 414), wherein the glutamic acid residue at position 1, the leucine residue at position 21, and the serine residue at position 22 of SEQ ID NO: 414 are each independently and optionally substituted by a residue from the donor sequence;
WYQQKPGQAPRLLIY (FR2) (SEQ ID NO: 416), wherein the leucine residue at position 13 of SEQ ID NO: 416 is optionally substituted by a residue from the donor sequence;
GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC (FR3) (SEQ ID NO: 418), wherein the isoleucine residue at position 2, the phenylalanine residue at position 27, and the valine residue at position 29 of SEQ ID NO: 418 are each independently and optionally substituted by a residue from the donor sequence; and
FGQGTKVEIK (FR4) (SEQ ID NO: 420), wherein the glutamine residue at position 3 and the valine residue at position 7 of SEQ ID NO: 420 are each independently and optionally substituted by a residue from the donor sequence.

11. The humanized light chain of claim 10 , wherein the amino acid at position 1 of SEQ ID NO: 414 is glutamine, the amino acid at position 21 of SEQ ID NO: 414 is methionine, isoleucine, or leucine, and the amino acid at position 22 of SEQ ID NO: 414 is threonine.

12. The humanized light chain of claim 10 , wherein the amino acid at position 13 of SEQ ID NO: 416 is tryptophan.

13. The humanized light chain of claim 10 , wherein the amino acid at position 2 of SEQ ID NO: 418 is valine, the amino acid at position 27 of SEQ ID NO: 418 is alanine, and the amino acid at position 29 of SEQ ID NO: 418 is threonine.

14. The humanized light chain of claim 10 , wherein the amino acid at position 3 of SEQ ID NO: 420 is alanine or serine and the amino acid at position 7 of SEQ ID NO: 420 is leucine.

15. The humanized light chain of claim 10 , wherein the amino acid at position 1 of SEQ ID NO: 428 is a charged amino acid and the amino acid at position 4 of SEQ ID NO: 428 is a charged amino acid.

16. The humanized light chain of claim 15 , wherein the amino acid at position 1 of SEQ ID NO: 414 is glutamine, the amino acid at position 21 of SEQ ID NO: 414 is methionine, isoleucine, or leucine, and the amino acid at position 22 of SEQ ID NO: 414 is threonine; the amino acid at position 13 of SEQ ID NO: 416 is tryptophan; the amino acid at position 2 of SEQ ID NO: 418 is valine, the amino acid at position 27 of SEQ ID NO: 418 is alanine, and the amino acid at position 29 of SEQ ID NO: 418 is threonine; and the amino acid at position 3 of SEQ ID NO: 420 is alanine or serine and the amino acid at position 7 of SEQ ID NO: 420 is leucine.

Assignees

• Abbvie Stemcentrx Llc

Inventors

• Stull Robert A
• Saunders Laura
• Dylla Scott J
• Foord Orit
• Liu David
• Torgov Michael
• Shao Hui

Classifications

• G01N33/5759

  involving compounds localised on the membrane of tumour or cancer cells · CPC title

• G01N33/5752

  of the lungs · CPC title

• A61K47/68035

  the drug being a pyrrolobenzodiazepine · CPC title

• C07K16/28 Primary

  against receptors, cell surface antigens or cell surface determinants · CPC title

• C07K2317/70

  characterized by effect upon binding to a cell or to an antigen · CPC title