Anti-TEM1 antibodies and uses thereof

Patent metadata

Field	Value
Publication number	US-9556272-B2
Application number	US-201013508925-A
Country	US
Kind code	B2
Filing date	Nov 12, 2010
Priority date	Nov 11, 2009
Publication date	Jan 31, 2017
Grant date	Jan 31, 2017

Abstract

The invention relates to Anti-TEM 1 anti-bodies or antigen-binding fragments thereof, yeast libraries comprising the same, and prophylactic, diagnostic, and therapeutic methods using the same.

First claim

What is claimed is:

1. An isolated monoclonal antibody or antigen-binding fragment thereof, whereby said antibody or antigen-binding fragment is specific for both the mouse and human form of an endosialin tumor endothelial marker 1 (TEM1) and binds to an epitope sequence as set forth in SEQ ID NO: 40, wherein the antibody or antigen-binding fragment comprises a heavy chain variable region comprising a CDR1 sequence of residues 31 to 35 of SEQ ID NO: 43; a CDR2 sequence of residues 50 to 65 of SEQ ID NO: 43; and a CDR3 sequence of residues 98 to 102 of SEQ ID NO: 43, and wherein the antibody or antigen-binding fragment comprises a light chain variable region comprising a CDR1 sequence of residues 23 to 36 of SEQ ID NO: 48; a CDR2 sequence of residues 52 to 62 of SEQ ID NO: 48; and a CDR3 sequence of residues 97 to 104 of SEQ ID NO: 48.

2. The antibody of claim 1 , wherein said antibody comprises a modification.

3. The antibody of claim 2 , whereby said modification minimizes conformational changes during the shift from displayed to secreted forms of said antibody or antigen binding fragment.

4. The antibody of claim 2 , wherein said modification is a N-terminus or a C-terminus modification.

5. The antibody of claim 4 , wherein said modification is a biotinylation.

6. The antibody of claim 5 , whereby said biotinylation allows binding to any surface coated with streptavidin, avidin, avidin-derived moieties, or a secondary reagent.

7. The antibody of claim 6 , whereby said secondary reagent is a protein, a peptide, a carbohydrate, or a glycoprotein.

8. The antibody of claim 1 , wherein said antigen-binding fragment is a single chain Fv (scFv), a scFv-Fc bivalent molecule, an Fab, Fab′, Fv, or F(ab′)2.

9. The antibody or antigen-binding fragment of claim 8 , wherein said antigen-binding fragment thereof is high affinity anti-TEM1 scFv-78 with a heavy chain variable region comprising SEQ ID NO: 43 and a light chain variable region comprising SEQ ID NO: 48.

10. The antibody or antigen-binding fragment of claim 9 , whereby biotinylating said scFv-78 at the N-terminus generates biobody-78.

11. The antibody or antigen-binding fragment of claim 10 , whereby said biobody-78 strongly binds to cell lines transduced with human TEM1 and cells that express high and moderate levels of endogenous human or mouse TEM1.

12. A method of treating, inhibiting or suppressing a tumor in a subject comprising the step of contacting said tumor cell with a composition comprising said antibody or antigen-binding fragment thereof of claim 1 that is operably linked to a biologically active agent, wherein said agent is a toxin, a radioisotope, a nanoparticle or a bio-active peptide.

13. The method of claim 12 , said composition further comprising proteolytic inhibitors, pharmaceutical carriers, diluents, and/or adjuvants.

14. A method of treating angiogenesis of a solid tumor in a subject, said method comprising the step of contacting a pericyte of said solid tumor with composition comprising said antibody or antigen-binding fragment thereof of claim 1 operably linked to a biologically active agent, wherein said agent is a toxin, a radioisotope, a nanoparticle or a bio-active peptide.

15. A method of delivering a biologically active agent and said antibody or antigen-binding fragment thereof of claim 1 for the treatment of a tumor in a subject, comprising the step of concomitantly but individually administering said biologically active agent and said antibody or antigen-binding fragment.

16. A method of delaying progression of a solid tumor in a subject, said method comprising administering to said subject an effective amount of said antibody or antigen binding fragment thereof from claim 1 , whereby said subject mounts an immune response against a pericyte of a vasculature of said solid tumor, thereby delaying progression of a solid tumor in a subject.

17. The antibody or antigen-binding portion thereof of claim 1 , wherein said marker is human or murine TEM 1.

18. The antibody or antigen-binding fragment of claim 1 , wherein the heavy chain variable region comprises the sequence set forth in SEQ ID NO: 43 and the light chain variable region comprises the sequence set forth in SEQ ID NO: 48.

Assignees

• Scholler Nathalie
• Zhao Aizhi
• Siegel Donald
• Coukos George
• Univ Pennsylvania

Inventors

• Scholler Nathalie
• Zhao Aizhi
• Siegel Donald
• Coukos George

Classifications

• C07K2317/21

  from primates, e.g. man · CPC title

• C07K16/2851 Primary

  against the lectin superfamily, e.g. CD23, CD72 · CPC title

• C07K2317/622

  Single chain antibody (scFv) · CPC title

• A61P39/00

  General protective or antinoxious agents · CPC title

• A61K2039/505

  comprising antibodies · CPC title