CD8-specific capture agents, compositions, and methods of using and making
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsHeather Dawn Agnew, Bert Tsunyin Lai
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Abstract
The present application provides stable peptide-based CD8 capture agents and methods of use as detection agents. The application further provides methods of manufacturing CD8 capture agents.
Claims13
A method of producing a synthetic capture agent that specifically binds to CD8 comprising
- (a) selecting a first ligand that binds to a first synthetic epitope of CD8 by screening a peptide library for epitope-templated in situ click reaction of the first synthetic epitope and a peptide in the peptide library that comprises a proparglyglycine;
- (b) selecting a second ligand that binds to a second synthetic epitope of CD8 by screening a peptide library for epitope-templated in situ click reaction of the second synthetic epitope and a peptide in the peptide library that comprises a proparglyglycine;
- and
- (c) covalently joining a linker to the first ligand and the second ligand, thereby producing the synthetic capture agent that binds to CD8,
- wherein the first synthetic epitope comprises the sequence SQFRVSPLD[Az4]TWNLGETVELKSQ (SEQ ID NO:
- 54) and the second synthetic epitope comprises the sequence FLLYLSQNKP[Az4]AAEGLDTQR (SEQ ID NO:
- 55).
A synthetic capture agent that binds to CD8, wherein the synthetic capture agent comprises a first ligand that is cyclic and 5-9 amino acids in length having affinity for a first epitope on CD8, a second ligand that is cyclic and 5-9 amino acids in length having affinity for a second epitope on CD8, and a linker covalently connecting the first ligand to the second ligand,
- wherein the first ligand comprises an amino acid sequence chosen from:
- (a)
- (SEQ ID NO:
- 6)
- HGSYG;
- (b)
- (SEQ ID NO:
- 7)
- KRLGA;
- (c)
- (SEQ ID NO:
- 8)
- AKYRG;
- (d)
- (SEQ ID NO:
- 9)
- hallw;
- (e)
- (SEQ ID NO:
- 10)
- lrGvw;
- (f)
- (SEQ ID NO:
- 11)
- vashf;
- (g)
- (SEQ ID NO:
- 12)
- nGnvh;
- (h)
- (SEQ ID NO:
- 13)
- wplrf;
- (i)
- (SEQ ID NO:
- 14)
- rwfnv;
- (j)
- (SEQ ID NO:
- 15)
- havwh;
- (k)
- (SEQ ID NO:
- 16)
- wvplw;
- (l)
- (SEQ ID NO:
- 17)
- ffrly;
- and
- (m)
- (SEQ ID NO:
- 18)
- wvvGf,
- and
- wherein the second ligand comprises an amino acid sequence chosen from:
- (a)
- (SEQ ID NO:
- 19)
- AGDSW;
- (b)
- (SEQ ID NO:
- 20)
- HVRHG;
- (c)
- (SEQ ID NO:
- 21)
- HGRGH;
- (d)
- (SEQ ID NO:
- 22)
- THPTT;
- (e)
- (SEQ ID NO:
- 23)
- FAGYH;
- (f)
- (SEQ ID NO:
- 24)
- WTEHG;
- (g)
- (SEQ ID NO:
- 25)
- PWTHG;
- (h)
- (SEQ ID NO:
- 26)
- TNDFD;
- (i)
- (SEQ ID NO:
- 27)
- LFPFD;
- (j)
- (SEQ ID NO:
- 28)
- slrfG;
- (k)
- (SEQ ID NO:
- 29)
- yfrGs;
- (l)
- (SEQ ID NO:
- 30)
- wnwvG;
- (m)
- (SEQ ID NO:
- 31)
- vawlG;
- (n)
- (SEQ ID NO:
- 32)
- fhvhG;
- (o)
- (SEQ ID NO:
- 33)
- wvsnv;
- (p)
- (SEQ ID NO:
- 34)
- wsvnv;
- (q)
- (SEQ ID NO:
- 35)
- lnshG;
- (r)
- (SEQ ID NO:
- 36)
- yGGvr;
- (s)
- (SEQ ID NO:
- 37)
- nsvhG;
- (t)
- (SEQ ID NO:
- 38)
- ttvhG;
- (u)
- (SEQ ID NO:
- 39)
- fdvGh;
- (v)
- (SEQ ID NO:
- 40)
- rhGwk;
- and
- (w)
- (SEQ ID NO:
- 49)
- hGrGh.
Dependencies are inferred from the claim text.