TGFBeta Antibodies, Methods and Uses
AssigneeScholar Rock, Inc.
InventorsGregory J. Carven, Thomas Schurpf, Katherine Turner
Life of this patent
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Abstract
ProTGFB1-GARP complex-selective antibodies, polynucleotides capable of encoding the proTGFB1-GARP complex-selective antibodies or antigen-binding fragments, cells expressing proTGFB1-GARP complex-selective antibodies or antigen-binding fragments, as well as associated vectors and detectably labeled proTGFB1-GARP complex-selective antibodies or antigen-binding fragments may be used to enhance an immune response in a subject, for example, against a cancer.
Claims23
An isolated antibody, or an antigen-binding fragment thereof,
- wherein the antibody or antigen binding fragment specifically binds to human proTGFβ1 in a complex with human glycoprotein A repetitions predominant (proTGFβ1-GARP complex) while said complex is in solution and the antibody or antigen binding fragment thereof has no detectable binding according to the biolayer interferometry assay using the experimental design described in Example 4 to any of the following agents:
- a TGFβ1 growth factor domain,
- a TGFβ2 growth factor domain,
- TGFβ3 growth factor domain,
- proTGFβ1 covalently associated with LTBP1,
- proTGFβ1 covalently associated with LTBP3,
- proTGFβ1 covalently associated with LRRC33, and
- proTGFβ1 that is unassociated with human GARP,
- a. as measured by OctetRed 384 under the conditions shown in Examples 4 and 6 and further wherein the antibody or antigen-binding fragment thereof has an inhibitory concentration (IC50) of less than or equal to 10 nM for inhibition of TGFβ1 growth factor release from a cell-associated proTGFβ1-GARP complex under the conditions shown in Example 5, wherein the antibody or antigen binding fragment comprises:
- b. a heavy chain CDR1 having the amino acid sequence of SEQ ID NO:
- 4, a heavy chain CDR2 having the amino acid sequence of SEQ ID NO:
- 5, and a heavy chain CDR3 having the amino acid sequence of SEQ ID NO:
- 6, a light chain CDR1 having the amino acid sequence of SEQ ID NO:
- 7, a light chain CDR2 having the amino acid sequence of SEQ ID NO:
- 8, and a light chain CDR3 having the amino acid sequence of SEQ ID NO:
- 9;
- or
- c. a heavy chain CDR1 having the amino acid sequence of SEQ ID NO:
- 10, a heavy chain CDR2 having the amino acid sequence of SEQ ID NO:
- 11, and a heavy chain CDR3 having the amino acid sequence of SEQ ID NO:
- 12, a light chain CDR1 having the amino acid sequence of SEQ ID NO:
- 13, a light chain CDR2 having the amino acid sequence of SEQ ID NO:
- 14, and a light chain CDR3 having the amino acid sequence of SEQ ID NO:
- 15.
(canceled)
An isolated antibody, or an antigen-binding fragment thereof, comprising a heavy chain variable region selected from the group consisting of the amino acid sequences of SEQ ID NOs:
- 16 and 18 and a light chain variable region selected from the group consisting of the amino acid sequences of SEQ ID NOs:
- 17 and 19.
(canceled)
An isolated antibody, or an antigen-binding fragment thereof, comprising:
- a. a heavy chain CDR1 having at least 80% identity to the amino acid sequence of SEQ ID NO:
- 4, a heavy chain CDR2 having at least 80% identity to the amino acid sequence of SEQ ID NO:
- 5, and a heavy chain CDR3 having at least 80% identity to the amino acid sequence of SEQ ID NO:
- 6, a light chain CDR1 having at least 80% identity to the amino acid sequence of SEQ ID NO:
- 7, a light chain CDR2 having at least 80% identity to the amino acid sequence of SEQ ID NO:
- 8, and a light chain CDR3 having at least 80% identity to the amino acid sequence of SEQ ID NO:
- 9;
- or
- b. a heavy chain CDR1 having at least 80% identity to the amino acid sequence of SEQ ID NO:
- 10, a heavy chain CDR2 having at least 80% identity to the amino acid sequence of SEQ ID NO:
- 11, and a heavy chain CDR3 having at least 80% identity to the amino acid sequence of SEQ ID NO:
- 12, a light chain CDR1 having at least 80% identity to the amino acid sequence of SEQ ID NO:
- 13, a light chain CDR2 having at least 80% identity to the amino acid sequence of SEQ ID NO:
- 14, and a light chain CDR3 having at least 80% identity to the amino acid sequence of SEQ ID NO:
- 15.
An isolated antibody, or an antigen-binding fragment thereof, comprising:
- a. a heavy chain variable region having at least 80% identity to the amino acid sequence of SEQ ID NO:
- 16 paired with a light chain variable region having at least 80% identity to the amino acid sequence of SEQ ID NO:
- 17;
- or
- b. a heavy chain variable region having at least 80% identity to the amino acid sequence of SEQ ID NO:
- 18 paired with a light chain variable region having at least 80% identity to the amino acid sequence of SEQ ID NO:
- 19.
Dependencies are inferred from the claim text.