Anti-endoglin antibodies and uses thereof
AssigneeTracon Pharmaceuticals, Inc.
InventorCharles Theuer
Life of this patent
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Abstract
The present application relates to compositions of humanized and 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 anti-endoglin antibodies which inhibit or treat fibrosis.
Claims41
A composition comprising an endoglin binding antibody or binding fragment thereof and a pharmaceutically acceptable excipient for use in treating or inhibiting a myelofibrosis or a neurofibromatosis, wherein the antibody or the antigen binding fragment thereof comprises a heavy chain variable region and a light chain variable region wherein:
- the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:89 optionally comprising 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 asparagine (Q) at position 52b;
- a substitution of leucine (L) by valine (V) at position 78 utilising the Kabat number system;
- and wherein the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:93 optionally comprising 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 utilising the Kabat number system;
- and a pharmaceutically acceptable excipient, whereby fibrosis is treated or inhibited.
A composition comprising an endoglin binding antibody or binding fragment thereof and a pharmaceutically acceptable excipient for use in treating or inhibiting a myelofibrosis or a neurofibromatosis, wherein the antibody or the antigen binding fragment thereof comprises 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 and a pharmaceutically acceptable excipient, whereby fibrosis is treated or inhibited.
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A method of treating or inhibiting a myelofibrosis or a neurofibromatosis in a subject in need thereof, comprising administering to the subject a composition comprising 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 and a pharmaceutically acceptable excipient, whereby fibrosis is treated or inhibited.
A method of treating or inhibiting a myelofibrosis or a neurofibromatosis in a subject in need thereof, comprising administering to the subject a composition comprising 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 asparagine (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;
- and a pharmaceutically acceptable excipient, whereby fibrosis is treated or inhibited.
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The method of clam 29, wherein the anti-endoglin antibody, or antigen-binding fragment and one or more fibrosis inhibitors are administered at different sites.
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Dependencies are inferred from the claim text.