Endoglin Antibodies
AssigneeTracon Pharmaceuticals, Inc.
InventorsCharles P. Theuer, Maximiliano Vasquez
Life of this patent
Estimating the term…
Abstract
The present application relates to compositions of humanized and humanized/deimmunized anti-endoglin antibodies and antigen-binding fragments thereof. One aspect relates to antibodies having one or more modifications in at least one amino acid residue of at least one of the framework regions of the variable heavy chain, the variable light chain or both. Another aspect relates to antibodies which bind endoglin and inhibit angiogenesis. Another aspect relates to the deimmunization of humanized antibodies to reduce immunogenicity. Another aspect relates to the use of humanized and humanized/deimmunized antibodies which bind endoglin for the detection, diagnosis or treatment of a disease or condition associated with endoglin, angiogenesis or a combination thereof.
Claims63
An antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region having an amino acid sequence set forth as SEQ ID NO:
- 89 and a light chain variable region having an amino acid sequence set forth as SEQ ID NO:
- 93.
An antibody, or antigen-binding fragment thereof, that binds endoglin, comprising a heavy chain variable region having an amino acid sequence set forth as SEQ ID NO:
- 89 and a light chain variable region having an amino acid sequence set forth as SEQ ID NO:
- 93, wherein:
- said heavy chain variable region further comprises one or more modifications selected from the group consisting of a substitution of glycine (G) by alanine (A) or serine (S) at position 49;
- a substitution of alanine (A) by isoleucine (I) at position 51;
- a substitution of lysine (K) by arginine (R) or glutamine (Q) at position 52b;
- a substitution of leucine (L) by valine (V) at position 78 utilizing the Kabat numbering system;
- and
- the light chain variable region further comprises one or more modifications selected from the group consisting of a substitution of methionine (M) by leucine (L) at position 4;
- a substitution of alanine (A) by valine (V) at position 19;
- a substitution of threonine (T) by serine (S) at position 22;
- a substitution of alanine (A) by isoleucine (I) at position 48;
- and a substitution of threonine (T) by serine (S) at position 51 utilizing the Kabat numbering system.
A diagnostic method comprising:
- a) providing a sample of cancer cells of a solid tumor or plasma from a patient to be tested;
- b) detecting in the sample the expression of at least one gene or gene product chosen from a panel of genes or gene products whose expression has been correlated with sensitivity or resistance to an angiogenesis inhibitor, wherein the at least one gene or gene product is chosen from one or more genes or gene products selected from the group consisting of VEGF, VEGF receptor, HIF-1α, placental growth factor receptor, and CD105;
- and
- c) comparing the level of expression of at least one gene or gene product detected in the patient sample to a level of expression of at least one gene or gene product that has been correlated with sensitivity or resistance to the angiogenesis inhibitor.
A kit comprising reagents for the detection of expression levels that have been correlated with sensitivity or resistance to an angiogenesis inhibitor of one or more genes selected from VEGF, VEGF receptor, HIF-1α, placental growth factor receptor, and endoglin in a sample of cancer cells or human plasma.
An antibody, or antigen-binding fragment thereof, that binds endoglin, that comprises a heavy chain variable region having an amino acid sequence set forth as SEQ ID NO:
- 88, 89, 90, 91 or 92 and a light chain variable region having an amino acid sequence set forth as SEQ ID NO:
- 93, 94, 95, or 102, wherein the antibody, or antigen-binding fragment thereof, has an affinity of from about 100 nanomolar (nM) to about 0.1 nM, from about 100 nM to about 1 picomolar (pM) or from about 100 nM to about 1 femtomolar (fM).
An antibody, or antigen-binding fragment thereof, that binds endoglin, that comprises a heavy chain variable region having an amino acid sequence set forth as SEQ ID NO:
- 88, 89, 90, 91 or 92 and a light chain variable region having an amino acid sequence set forth as SEQ ID NO:
- 93, 94, 95, or 102, wherein the antibody, or antigen-binding fragment thereof, has a KD of from about 5×10−10 or greater.
Dependencies are inferred from the claim text.