US2022106707A1PendingUtilityA1

Recombinant peptide-mhc complex binding proteins and their generation and use

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Assignee: MOLECULAR PARTNERS AGPriority: Dec 11, 2019Filed: Aug 2, 2021Published: Apr 7, 2022
Est. expiryDec 11, 2039(~13.4 yrs left)· nominal 20-yr term from priority
Inventors:Victor LevitskyNatalia VenetzMarcel WalserKaspar BinzJohannes SchillingPatrik Forrer
C07K 14/47A61K 38/00C40B 40/10C07K 2318/20C07K 2317/74C07K 2317/32C07K 16/3069C07K 16/082C07K 16/30C07K 2319/70C12N 15/62C07K 2317/92C07K 2317/73A61P 35/00G01N 33/575Y02A50/30
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Claims

Abstract

The present invention relates to a method of producing recombinant binding proteins with binding specificity for a peptide-MHC (pMHC) complex. The invention also relates to recombinant binding proteins comprising one, two or more designed repeat domain(s), preferably designed ankyrin repeat domain(s), with binding specificity for a pMHC complex, and to such binding proteins which further comprise a binding agent having binding specificity for a protein expressed on the surface of an immune cell, preferably a T-cell. In addition, the invention relates to nucleic acids encoding such binding proteins or repeat domains, pharmaceutical compositions comprising such binding proteins or nucleic acids, and the use of such binding proteins, nucleic acids or pharmaceutical compositions in methods for treating or diagnosing diseases, including cancer, infectious diseases and autoimmune diseases.

Claims

exact text as granted — not AI-modified
1 - 78 . (canceled) 
     
     
         79 . A library comprising designed ankyrin repeat proteins, wherein said designed ankyrin repeat proteins comprise an N-terminal capping module having the amino acid sequence of SEQ ID NO: 5, 6 or 7, wherein leucine (L) at position 17 of SEQ ID NO: 5, 6 or 7 is optionally substituted with valine (V), isoleucine (I), methionine (M), or alanine (A), and wherein G at position 1 and/or S at position 2 of SEQ ID NOs: 5 to 7 are optionally missing. 
     
     
         80 . The library comprising designed ankyrin repeat proteins of  claim 79 , wherein said designed ankyrin repeat proteins comprise an N-terminal capping module having the amino acid sequence of SEQ ID NO: 5, 6 or 7, wherein G at position 1 and/or S at position 2 of SEQ ID NOs: 5 to 7 are optionally missing. 
     
     
         81 . The library comprising designed ankyrin repeat proteins of  claim 79 , wherein said designed ankyrin repeat proteins comprise an N-terminal capping module having the amino acid sequence of SEQ ID NO: 5, 6 or 7. 
     
     
         82 . The library comprising designed ankyrin repeat proteins of  claim 79 , wherein said designed ankyrin repeat proteins comprise an N-terminal capping module having the amino acid sequence of SEQ ID NO: 5, wherein G at position 1 and/or S at position 2 of SEQ ID NO: 5 are optionally missing. 
     
     
         83 . The library comprising designed ankyrin repeat proteins of  claim 79 , wherein said designed ankyrin repeat proteins comprise an N-terminal capping module having the amino acid sequence of SEQ ID NO: 5. 
     
     
         84 . The library comprising designed ankyrin repeat proteins of  claim 79 , wherein said designed ankyrin repeat proteins comprise an N-terminal capping module having the amino acid sequence of SEQ ID NO: 6, wherein G at position 1 and/or S at position 2 of SEQ ID NO: 6 are optionally missing. 
     
     
         85 . The library comprising designed ankyrin repeat proteins of  claim 79 , wherein said designed ankyrin repeat proteins comprise an N-terminal capping module having the amino acid sequence of SEQ ID NO: 6. 
     
     
         86 . The library comprising designed ankyrin repeat proteins of  claim 79 , wherein said designed ankyrin repeat proteins comprise an N-terminal capping module having the amino acid sequence of SEQ ID NO: 7, wherein G at position 1 and/or S at position 2 of SEQ ID NO: 7 are optionally missing. 
     
     
         87 . The library comprising designed ankyrin repeat proteins of  claim 79 , wherein said designed ankyrin repeat proteins comprise an N-terminal capping module having the amino acid sequence of SEQ ID NO: 7. 
     
     
         88 . A designed ankyrin repeat protein selected from the library of  claim 79 . 
     
     
         89 . A designed ankyrin repeat protein selected from the library of  claim 82 . 
     
     
         90 . A designed ankyrin repeat protein selected from the library of  claim 83 . 
     
     
         91 . The designed ankyrin repeat protein of  claim 88 , wherein said designed ankyrin repeat protein has an amino acid sequence selected from SEQ ID NOs: 20-22, 29-33, 96, 105-110 and 167-173. 
     
     
         92 . A library comprising designed ankyrin repeat proteins, wherein said designed ankyrin repeat proteins comprise an N-terminal capping module having a leucine (L), valine (V), isoleucine (I), methionine (M), or alanine (A) at a position corresponding to position 17 of SEQ ID NO: 5. 
     
     
         93 . The library comprising designed ankyrin repeat proteins of  claim 92 , wherein said designed ankyrin repeat proteins comprise an N-terminal capping module having a leucine (L) at a position corresponding to position 17 of SEQ ID NO: 5. 
     
     
         94 . A designed ankyrin repeat protein selected from the library of  claim 92 . 
     
     
         95 . The designed ankyrin repeat protein of  claim 92 , wherein said designed ankyrin repeat protein has an amino acid sequence selected from SEQ ID NOs: 20-22, 29-33, 96-97, 105-110 and 167-173. 
     
     
         96 . A designed ankyrin repeat protein comprising an N-terminal capping module having the amino acid sequence of SEQ ID NO: 5, 6 or 7, wherein leucine (L) at position 17 of SEQ ID NO: 5, 6 or 7 is optionally substituted with valine (V), isoleucine (I), methionine (M), or alanine (A), and wherein G at position 1 and/or S at position 2 of SEQ ID NOs: 5 to 7 are optionally missing. 
     
     
         97 . The designed ankyrin repeat protein of  claim 96 , wherein said designed ankyrin repeat protein comprises an N-terminal capping module having the amino acid sequence of SEQ ID NO: 5, 6 or 7, wherein G at position 1 and/or S at position 2 of SEQ ID NOs: 5 to 7 are optionally missing. 
     
     
         98 . The designed ankyrin repeat protein of  claim 96 , wherein said designed ankyrin repeat protein comprises an N-terminal capping module having the amino acid sequence of SEQ ID NO: 5, 6 or 7. 
     
     
         99 . The designed ankyrin repeat protein of  claim 96 , wherein said designed ankyrin repeat protein comprises an N-terminal capping module having the amino acid sequence of SEQ ID NO: 5, wherein G at position 1 and/or S at position 2 of SEQ ID NO: 5 are optionally missing. 
     
     
         100 . The designed ankyrin repeat protein of  claim 96 , wherein said designed ankyrin repeat protein comprises an N-terminal capping module having the amino acid sequence of SEQ ID NO: 5. 
     
     
         101 . The designed ankyrin repeat protein of  claim 96 , wherein said designed ankyrin repeat protein comprises an N-terminal capping module having the amino acid sequence of SEQ ID NO: 6, wherein G at position 1 and/or S at position 2 of SEQ ID NO: 6 are optionally missing. 
     
     
         102 . The designed ankyrin repeat protein of  claim 96 , wherein said designed ankyrin repeat protein comprises an N-terminal capping module having the amino acid sequence of SEQ ID NO: 6. 
     
     
         103 . The designed ankyrin repeat protein of  claim 96 , wherein said designed ankyrin repeat protein comprises an N-terminal capping module having the amino acid sequence of SEQ ID NO: 7, wherein G at position 1 and/or S at position 2 of SEQ ID NO: 7 are optionally missing. 
     
     
         104 . The designed ankyrin repeat protein of  claim 96 , wherein said designed ankyrin repeat protein comprises an N-terminal capping module having the amino acid sequence of SEQ ID NO: 7. 
     
     
         105 . The designed ankyrin repeat protein of  claim 96 , wherein said designed ankyrin repeat protein has an amino acid sequence selected from SEQ ID NOs: 20-22, 29-33, 96, 105-110 and 167-173. 
     
     
         106 . A designed ankyrin repeat protein comprising an N-terminal capping module having a leucine (L), valine (V), isoleucine (I), methionine (M), or alanine (A) at a position corresponding to position 17 of SEQ ID NO: 5. 
     
     
         107 . The designed ankyrin repeat protein of  claim 106 , wherein said designed ankyrin repeat protein comprises an N-terminal capping module having a leucine (L) at a position corresponding to position 17 of SEQ ID NO: 5. 
     
     
         108 . The designed ankyrin repeat protein of  claim 106 , wherein said designed ankyrin repeat protein has an amino acid sequence selected from SEQ ID NOs: 20-22, 29-33, 96-97, 105-110 and 167-173.

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