Novel antigen-binding polypeptides and their uses

• US 20060153860A1
• Filed: 06/17/2005
• Published: 07/13/2006
• Est. Priority Date: 06/18/2004
• Status: Active Grant

• Current Assignee: Ambrx, Inc. (Johnson & Johnson)
• Original Assignee: Ambrx, Inc. (Johnson & Johnson)
• Inventors: Tian, Feng, Cho, Ho Sung, Hays, Anna-Maria, Daniel, Thomas O., Wilson, Troy E., Ho, Lillian, Cujec, Thomas P., Kimmel, Bruce E.
• Granted Patent: US 7,632,924 B2
• Time in Patent Office: Days
• US Class Current: 424/185.100
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: C07K 14/195 from bacteria
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: C07K 16/2863 against receptors for growth factors, growth regulators
• CPC Class Codes: C07K 16/32 against translation products of oncogenes
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/41 Glycosylation, sialylation, or fucosylation
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)

Abstract

Novel antigen-binding polypeptides (ABP) and uses thereof are provided.

Claims

1. An antigen-binding polypeptide comprising one or more non-naturally encoded amino acids.

2. The antigen-binding polypeptide of claim 1, wherein the antigen-binding polypeptide comprises one or more post-translational modifications.

3. The antigen-binding polypeptide of claim 1, wherein the antigen-binding polypeptide is linked to a linker, polymer, or biologically active molecule.

5. A method of making the antigen-binding polypeptide of claim 3, the method comprising contacting an isolated antigen-binding polypeptide comprising a non-naturally encoded amino acid with a linker, polymer, or biologically active molecule comprising a moiety that reacts with the non-naturally encoded amino acid.

6. A composition comprising the antigen-binding polypeptide of claim 1 and a pharmaceutically acceptable carrier.

7. A method of treating a patient having a disorder modulated by ABP comprising administering to the patient a therapeutically-effective amount of the composition of claim 6.

23. The antigen-binding polypeptide of claim 3, wherein the antigen-binding polypeptide is linked to the linker, polymer, or biologically active molecule under denaturing conditions.

4. An isolated nucleic acid comprising a polynucleotide that hybridizes under stringent conditions to an antigen-binding polypeptide-encoding polynucleotide, wherein the polynucleotide comprises at least one selector codon.

8. A cell comprising the nucleic acid of claim 4.

9. A method of making an antigen-binding polypeptide comprising a non-naturally encoded amino acid, the method comprising, culturing cells comprising a polynucleotide or polynucleotides encoding an antigen-binding polypeptide comprising a selector codon, an orthogonal RNA synthetase and an orthogonal tRNA under conditions to permit expression of the antigen-binding polypeptide comprising a non-naturally encoded amino acid;

and purifying the antigen-binding polypeptide.

10. A method of modulating serum half-life or circulation time of an antigen-binding polypeptide, the method comprising substituting one or more non-naturally encoded amino acids for any one or more naturally occurring amino acids in the antigen-binding polypeptide.

11. An antigen-binding polypeptide encoded by a polynucleotide wherein said polynucleotide comprises a selector codon, and wherein said polypeptide comprises at least one non-naturally encoded amino acid.

12. A composition comprising the antigen-binding polypeptide of claim 11 and a pharmaceutically acceptable carrier.

13. A bispecific ABP comprising a first ABP and a second ABP joined to each other wherein said first ABP and said second ABP bind specifically to different epitopes wherein said first ABP has binding specificity for at least one epitope on a first antigen, and the second ABP has binding specificity for a second epitope on the first antigen or a second antigen which is different from said first epitope, and wherein said bispecific ABP comprises at least one non-naturally encoded amino acid.

14. A composition comprising a bispecific ABP of claim 13 and a pharmaceutically acceptable carrier.

15. A method for treating a disease or condition, said method comprising administering to a patient in need thereof a therapeutically effective amount of the composition of claim 14.

16. An ABP comprising the bispecific ABP of claim 13, coupled to a biologically active molecule.

17. A method of detecting a cell or tissue expressing one or more antigens, said method comprising:

contacting a cell or tissue with an ABP of claim 13 attached to a detectable label; and

detecting said label wherein detection of said label in association with a cell or tissue indicates the presence of a cell or tissue expressing one or more antigens bound by the ABP.

18. An antigen-binding polypeptide comprising a water soluble polymer linked by a covalent bond to the antigen-binding polypeptide at a single amino acid.

19. An antigen-binding polypeptide comprising at least one linker, polymer, or biologically active molecule, wherein said linker, polymer, or biologically active molecule is attached to the polypeptide through a functional group of a non-naturally encoded amino acid ribosomally incorporated into the polypeptide.

20. An antigen-binding polypeptide comprising a linker, polymer, or biologically active molecule that is attached to one or more non-naturally encoded amino acids wherein said non-naturally encoded amino acid is ribosomally incorporated into the polypeptide at pre-selected sites.

21. A method of modulating immunogenicity of an antigen-binding polypeptide, the method comprising substituting one or more non-naturally encoded amino acids for any one or more naturally occurring amino acids in the antigen-binding polypeptide.

22. An antigen-binding polypeptide wherein the polypeptide is selected from the group consisting of SEQ ID NO:

19, 21, 23, 24, 26, 28, 30, 31 or fragment thereof.