Anti-tumor endothelial marker-1 (TEM1) antibody variants and uses thereof

• US 9,783,610 B2
• Filed: 03/15/2013
• Issued: 10/10/2017
• Est. Priority Date: 04/27/2012
• Status: Active Grant

• Current Assignee: Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Original Assignee: Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Inventors: Coukos, George, Li, Chunsheng
• Primary Examiner(s): Huff, Sheela J
• Application Number:
  US14/397,128
• Publication Number:
  US 20150125385A1
• Time in Patent Office: 1,670 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 51/1045 against animal or human tumor cells or tumor cell determinants
• CPC Class Codes: C07K 16/2851 against the lectin superfamily, e.g. CD23, CD72
• CPC Class Codes: C07K 2317/14 Specific host cells or culture conditions, e.g. components, pH or temperature
• CPC Class Codes: C07K 2317/30 characterized by aspects of specificity or valency
• CPC Class Codes: C07K 2317/33 Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
• CPC Class Codes: C07K 2317/524 CH2 domain
• CPC Class Codes: C07K 2317/526 CH3 domain
• CPC Class Codes: C07K 2317/53 Hinge
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/77 Internalization into the cell
• CPC Class Codes: C07K 2317/90 characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C07K 2317/94 Stability, e.g. half-life, pH, temperature or enzyme-resistance
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: G01N 33/57492 involving compounds localized on the membrane of tumor or cancer cells

Abstract

The invention relates to variants of an antibody or antigen-binding fragment that binds specifically to an endosialin tumor endothelial marker 1 (TEM1), and prophylactic, diagnostic, and therapeutic methods using the same.

Claims

1. An anti-tumor endothelial marker-1 (TEM-1) antigen-binding fragment dimer comprising two anti-TEM1 antigen-binding fragments, wherein each antigen-binding fragment comprises a single chain variable region and a hinge region, wherein the two antigen-binding fragments are linked through the two hinge regions, wherein said antigen-binding fragments specifically bind an epitope situated between TEM1 amino acids 324 and 390, wherein each monomer further comprises an antibody constant region comprising an Fc region, and wherein said antigen-binding fragment is scFv78-Fc, and the amino acid sequence of said scFv78-Fc comprises the sequence set forth in SEQ ID NO:

44.

2. An anti-tumor endothelial marker-1 (TEM1) antigen-binding fragment dimer comprising two anti-TEM1 antigen-binding fragments, wherein each antigen-binding fragment comprises a single chain variable region and a hinge region, wherein the two antigen-binding fragments are linked through the two hinge regions, wherein said antigen-binding fragments specifically bind an epitope situated between TEM1 amino acids 324 and 390, wherein each monomer further comprises an antibody constant region comprising a CH2 constant region, and wherein said antigen-binding fragment is scFv78CH2, and the amino acid sequence of said scFv78CH2 comprises the sequence set forth in SEQ ID NO:

46.

3. An anti-tumor endothelial marker-1 (TEM1) antigen-binding fragment dimer comprising two anti-TEM1 antigen-binding fragments, wherein each antigen-binding fragment comprises a single chain variable region and a hinge region, wherein the two antigen-binding fragments are linked through the two hinge regions, wherein said antigen-binding fragments specifically bind an epitope situated between TEM1 amino acids 324 and 390, wherein each monomer further comprises an antibody constant region comprising an Fc region, and wherein said antigen-binding fragment is scFv78CH3, and the amino acid sequence of said scFv78CH3 comprises the sequence set forth in SEQ ID NO:

48.

4. An anti-tumor endothelial marker-1 (TEM1) antigen-binding fragment dimer comprising two anti-TEM1 antigen-binding fragments, wherein each antigen-binding fragment comprises a single chain variable region and a hinge region, wherein the two antigen-binding fragments are linked through the two hinge regions, wherein said antigen-binding fragments specifically bind an epitope situated between TEM1 amino acids 324 and 390, and wherein said antigen-binding fragment is scFv78-minibody and the amino acid sequence of said scFv78-minibody comprises the sequence set forth in SEQ ID NO:

50.