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US 2026/0297198 A1Published application
Compositions and methods involving integrin alpha3beta1
Assignees149 Bio, LLC, Rush University Medical Center
InventorsSantiago Balza Pineda, Darlah Lopez-Rodriguez, Carl J. Abrahams, Antonio J. Barbosa, Vineet Gupta
Life of this patent
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Abstract
Compositions and methods comprising antibodies that bind to integrin α3β1 are provided.
Claims39
An isolated antibody that binds to an integrin α3β1 or a portion thereof, comprising:
- (1) a heavy chain complementarity-determining region 1 (CDR H1) comprising the sequence of X1X2SGX3TFX4X5YX6X7X8 (SEQ ID NO:38), wherein X1 is A or K;
- X2 is A or T;
- X3 is F, G, or Y;
- X4 is S or T;
- X5 is S or N;
- X6 is G, S, or A;
- X7 is M or I;
- and X8 is H, N, or S;
- (2) a CDR H2 comprising a sequence having up to two amino acid substitutions relative to the sequence of GISGSADTTY (SEQ ID NO:6), SISSSSSYIY (SEQ ID NO:9), or GIIPIFGTAN (SEQ ID NO:10), or the sequence of WISAX1NGNX2N (SEQ ID NO:39), wherein X1 is Y or N;
- and X2 is T or S;
- (3) a CDR H3 comprising a sequence having up to two amino acid substitutions relative to the sequence of VRDDIQLRD (SEQ ID NO:11) or AREFPGWYFDY (SEQ ID NO:13), or a sequence having up to four amino acid substitutions relative to the sequence of
- (SEQ ID NO:
- 12)
- ARDYSGSWYPSNGPALDY,
- (SEQ ID NO:
- 14)
- AREYYDFWSGYPSGYAFDI,
- or
- (SEQ ID NO:
- 15)
- ARGVPSGSGYYLGLDY;
- (4) a light chain complementarity-determining region 1 (CDR L1) comprising the sequence of X1ASQX2ISX3YLN (SEQ ID NO:40), wherein X1 is Q or A;
- X2 is D or Y;
- and X3 is N or S, or a sequence having up to three amino acid substitutions relative to the sequence of
- (SEQ ID NO:
- 23)
- QGDSLRSYYAS
- or
- (SEQ ID NO:
- 24)
- SGSSSNIGSNYVY;
- (5) a CDR L2 comprising a sequence having up to one amino acid substitution relative to the sequence of YDASNLET (SEQ ID NO:25), or the sequence of YX1X2NX3RPS (SEQ ID NO:41), wherein X1 is G or R;
- X2 is K or N;
- and X3 is N or Q;
- and
- (6) a CDR L3 comprising the sequence of X1QX2YX3X4PX5T (SEQ ID NO:42), wherein X1 is L or Q;
- X2 is D or S;
- X3 is N, S, or R;
- X4 is Y or T;
- and X5 is L or P, or a sequence having up to two amino acid substitutions relative to the sequence of NSRDSSGNHWV (SEQ ID NO:31) or AAWDDSLSGPV (SEQ ID NO:32).
37 more elements
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-39. (canceled)
-48. (canceled)
A method for identifying antibodies that bind to an integrin α3β1 or a portion thereof, comprising:
- 1) removing antibodies that bind against the β1 chain of the integrin α3β1 in the presence or absence of a ligand mimetic peptide and/or an antibody;
- 2) from the remaining antibodies from step 1), selecting for antibodies that bind to the integrin α3β1 in the presence or absence of a β1 agonist antibody;
- 3) counter selecting for antibodies that bind to the integrin α3β1 against immobilized β1 agonist antibodies or a ligand mimetic peptide alone;
- and
- 4) repeating steps 1), 2), and 3) above to enrich for antibodies that are integrin α3 allosteric agonists in the presence of cell surface-expressed integrin α3β1.
2 more elements
-51. (canceled)
Dependencies are inferred from the claim text.