US2020308304A1PendingUtilityA1

Hinge modified antibody fragments and methods of making

54
Assignee: GENENTECH INCPriority: Oct 30, 2015Filed: Apr 17, 2020Published: Oct 1, 2020
Est. expiryOct 30, 2035(~9.3 yrs left)· nominal 20-yr term from priority
Inventors:Yu-Ju G. MengHok Seon KimIngrid KimChristoph Spiess
C07K 16/4283C07K 2317/53C07K 2317/34C07K 2317/71C07K 2317/52A61P 43/00C07K 2317/76C07K 2317/55C07K 2317/94C07K 2317/54C07K 2317/75
54
PatentIndex Score
0
Cited by
0
References
0
Claims

Abstract

The instant disclosure provides antibody fragments (e.g., Fab and F(ab′)2) having reduced or no reactivity towards pre-existing anti-hinge antibodies (AHA) and compositions comprising such antibody fragments, as well as methods of making and using such antibody fragments and compositions.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A composition comprising an isolated Fab antibody fragment, wherein the Fab antibody fragment has reduced or no reactivity towards pre-existing anti-hinge antibodies. 
     
     
         2 . The composition of  claim 1 , wherein the Fab antibody fragment is an IgG1 Fab. 
     
     
         3 . The composition of  claim 2 , wherein the IgG1 Fab terminates with residue D 221.    
     
     
         4 . The composition of  claim 2 , wherein the IgG1 Fab terminates with residue K222. 
     
     
         5 . The composition of  claim 2 , wherein the IgG1 Fab comprises a T225X mutation, wherein X is any amino acid except T. 
     
     
         6 . The composition of  claim 2 , wherein the IgG1 Fab terminates with amino acids comprising an amino acid sequence selected from the group consisting of CDKTHT (SEQ ID NO: 4), CDKTHL (SEQ ID NO: 15), CDKTH (SEQ ID NO: 16), CDKT (SEQ ID NO: 17), CDK and CD. 
     
     
         7 . The composition of  claim 6 , wherein the IgG1 Fab terminates with amino acids comprising the amino acid sequence CDKTHT (SEQ ID NO: 4) 
     
     
         8 . The composition of  claim 6 , wherein the IgG1 Fab terminates with amino acids comprising the amino acid sequence CDKTHL (SEQ ID NO: 15). 
     
     
         9 . The composition of  claim 6 , wherein the IgG1 Fab terminates with amino acids comprising the amino acid sequence CDKTH (SEQ ID NO: 16). 
     
     
         10 . The composition of  claim 6 , wherein the IgG1 Fab terminates with amino acids comprising the amino acid sequence CDKT (SEQ ID NO: 17). 
     
     
         11 . The composition of  claim 6 , wherein the IgG1 Fab terminates with amino acids comprising the amino acid sequence CDK. 
     
     
         12 . The composition of  claim 6 , wherein the IgG1 Fab terminates with amino acids comprising the amino acid sequence CD. 
     
     
         13 . The composition of  claim 1 , wherein the Fab antibody fragment is an IgG4 Fab. 
     
     
         14 . The composition of  claim 13 , wherein the IgG4 Fab terminates with amino acids comprising an amino acid sequence selected from group consisting of KYGPP (SEQ ID NO: 18), KYGP (SEQ ID NO: 19), KYG and KY. 
     
     
         15 . The composition of  claim 14 , wherein the IgG4 Fab terminates with amino acids comprising the amino acid sequence KYGPP (SEQ ID NO: 18). 
     
     
         16 . The composition of  claim 14 , wherein the IgG4 Fab terminates with amino acids comprising the amino acid sequence KYGP (SEQ ID NO: 19). 
     
     
         17 . The composition of  claim 14 , wherein the IgG4 Fab terminates with amino acids comprising the amino acid sequence KYG. 
     
     
         18 . The composition of  claim 14 , wherein the IgG4 Fab terminates with amino acids comprising the amino acid sequence KY. 
     
     
         19 . The composition of  claim 13 , wherein the IgG4 Fab terminates with residue K218. 
     
     
         20 . The composition of  claim 1 , wherein the Fab antibody fragment comprises a heavy chain constant region that comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and conservative modifications of. 
     
     
         21 . The composition of  claim 1 , wherein the Fab antibody fragment exhibits reduced binding to FcγRIIIa, C1q or a combination thereof. 
     
     
         22 . A pharmaceutical formulation comprising the composition of  claim 1  and a pharmaceutically acceptable carrier.

Join the waitlist — get patent alerts

Track US2020308304A1 — get alerts on status changes and closely related new filings.

We store only your email — no account needed. See our privacy policy.