Binding proteins that bind to human FGFR1C, human β-klotho and both human FGFR1C and human β-klotho
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C07K-001/00
C07K-014/00
출원번호
US-0958209
(2010-12-01)
등록번호
US-8372952
(2013-02-12)
발명자
/ 주소
Smith, Richard
Bakker, Alice
Duguay, Amy N.
Li, Peng
Li, Yang
출원인 / 주소
Amgen Inc.
인용정보
피인용 횟수 :
10인용 특허 :
70
초록
Binding proteins that specifically bind to β-Klotho or portions thereof, FGFR1c or portions thereof, or both FGFR1c and β-Klotho, and optionally other proteins as well are provided. Coding sequences, methods of treatment and pharmaceutical compositions are also provided.
대표청구항▼
1. A binding protein that selectively binds β-Klotho and Fibroblast Growth Factor Receptor 1c (“FGFR1c”) comprising (a) one or more domains that selectively bind β-Klotho, and (b) one or more domains that selectively bind FGFR1c, wherein the binding protein comprises: (a) a β-Klotho binding domain c
1. A binding protein that selectively binds β-Klotho and Fibroblast Growth Factor Receptor 1c (“FGFR1c”) comprising (a) one or more domains that selectively bind β-Klotho, and (b) one or more domains that selectively bind FGFR1c, wherein the binding protein comprises: (a) a β-Klotho binding domain comprising: (SEQ ID NO: 257)CGADQFRCGNGSCVPRAWRCDGVDDCGDGSDEAPEIC;(b) an FGFR1c binding domain comprising: (SEQ ID NO: 108)CG[AE][GS]LFTC[GR][NRS][AST][KN]ICIS[EHQS][AV]W[IV]CDG[IV]DDC[DE]DNSDE[DKMNT][NSY]C, wherein the FGFR1c binding domain retains the ability to bind FGFR1c; andwherein amino acids in brackets indicate alternative amino acids at a specified position and “−” indicates no amino acid at the specified position. 2. The binding protein of claim 1 further comprising at least one linker joining (a) and (b). 3. The binding protein of claim 2, wherein the linker comprises: SAPASEPPGSL (SEQ ID NO: 12). 4. The binding protein of claim 3, wherein the FGFR1c binding domain of (b) comprises one or more of: (SEQ ID NO: 109)CGAGLFTCRS TNICISQVWV CDGVDDCEDN SDEDSC;(SEQ ID NO: 110)CGAGLFTCRS TNICISQAWV CDGVDDCEDN SDENYC;(SEQ ID NO: 111)CGAGLFTCRS TNICISQAWV CDGVDDCEDN SDETNC;(SEQ ID NO: 112)CGEGLFTCGS TNICISSAWV CDGVDDCEDN SDENNC;(SEQ ID NO: 113)CGEGLFTCRS TNICISHAWV CDGVDDCEDN SDENNC;(SEQ ID NO: 114)CGEGLFTCRS TNICISEAWI CDGVDDCEDN SDEKNC;(SEQ ID NO: 115)CGAGLFTCRS AKICISHAWV CDGIDDCEDN SDENNC;(SEQ ID NO: 116)CGAGLFTCRN SKICISQAWV CDGVDDCDDN SDEKYC;(SEQ ID NO: 117)CGASLFTCRR SNICISQAWV CDGVDDCEDN SDEMNC;and(SEQ ID NO: 118)CGAGLFTCRS TKICISQAWV CDGVDDCEDN SDEKNC. 5. The binding protein of claim 4, wherein the FGFR1c binding domain of (b) further comprises a linker comprising the sequence SAPASEPPGSL (SEQ ID NO: 12). 6. The binding protein of claim 5, wherein the FGFR1c binding domain comprises one or more of: (SEQ ID NO: 293)CGAGLFTCRSTNICISQVWVCDGVDDCEDNSDEDSCSAPASEPPGSL;(SEQ ID NO: 294)CGAGLFTCRSTNICISQAWVCDGVDDCEDNSDENYCSAPASEPPGSL;(SEQ ID NO: 295)CGAGLFTCRSTNICISQAWVCDGVDDCEDNSDETNCSAPASEPPGSL;(SEQ ID NO: 448)CGEGLFTCGSTNICISSAWVCDGVDDCEDNSDENNCSAPASEPPGSL;(SEQ ID NO: 297)CGEGLFTCRSTNICISHAWVCDGVDDCEDNSDENNCSAPASEPPGSL;(SEQ ID NO: 449)CGEGLFTCRSTNICISEAWICDGVDDCEDNSDEKNCSAPASEPPGSL;(SEQ ID NO: 450)CGAGLFTCRSAKICISHAWVCDGIDDCEDNSDENNCSAPASEPPGSL;(SEQ ID NO: 464)CGAGLFTCRNSKICISQAWVCDGVDDCDDNSDEKYCSAPASEPPGSL;(SEQ ID NO: 296)CGASLFTCRRSNICISQAWVCDGVDDCEDNSDEMNCSAPASEPPGSL;and(SEQ ID NO: 287)CGAGLFTCRSTKICISQAWVCDGVDDCEDNSDEKNCSAPASEPPGSL. 7. A binding protein that selectively binds β-Klotho and FGFR1c comprising (a) one or more domains that selectively bind β-Klotho, and (b) one or more domains that selectively bind FGFR1c, wherein the binding protein comprises: (a) a β-Klotho binding domain comprising: (i) a first binding domain comprising: (SEQ ID NO: 257)CGADQFRCGNGSCVPRAWRCDGVDDCGDGSDEAPEIC;(ii) a second binding domain comprising one or more of: (SEQ ID NO: 394)CQSNEFRCRSGRCIPQHWLCDGLNDCGDGSDE[PS][PQ][AQ][-H]C;(SEQ ID NO: 217)C[ELPQR][APS][DGIN][EGQ][FQ][FKPQRT][-E]C[GNRS][NS]G[HNQR]C[IV]P[AELPQRV][AHPQRT]W[LRV]CDG[DEV][DNP]DC[GLQ]D[DGNS]SDE[AEKT][DGLNS][-A][-H]C;and(SEQ ID NO: 254)C[AGP][APS][DGN][EQ]F[QRT]C[GNRS][GNS][GT][GKQS][-IK]C[ILV]P[LQRV][AEHP]W[LRV]CDG[DLV][DN]DCGD[GN]SDE[AEKPS][GLPS][-AEV][-IT]C, wherein the second binding domain retains the ability to bind β-Klotho; and(iii) a linker joining the first binding domain and the second binding domain; and(b) an FGFR1c binding domain comprising a sequence selected from the group represented by the sequence: (SEQ ID NO: 108)CG[AE][GS]LFTC[GR][NRS][AST][KN]ICIS[EHQS][AV]W[IV]CDG[IV]DDC[DE]DNSDE[DKMNT][NSY]C wherein the FGFR1c binding domain retains the ability to bind FGFR1c; and(c) a linker joining the sequences of (a) and (b),wherein amino acids in brackets indicate alternative amino acids at a specified position and “−” indicates no amino acid at the specified position. 8. The binding protein of claim 7, wherein the second binding domain of (a) comprises one or more of: (SEQ ID NO: 481)CQSNEFRCRSGRCIPQHWLCDGLNDCGDGSDESQQCSAPASEPPGSL (SEQ ID NO: 159)CQSNEFRCRSGRCIPQHWLCDGLNDCGDGSDESQQC;(SEQ ID NO: 1323)CRAGEFRCSNGRCVPLTWLCDGEDDCQDNSDEKNC;(SEQ ID NO: 1324)CPSNQFPCRSTGICIPLAWVCDGLNDCGDGSDESPAHC;and(SEQ ID NO: 1325)CQSNEFRCRSGRCIPQHWLCDGLNDCGDGSDEPPAHC. 9. The binding protein of claim 8, wherein the linker of (a) comprises: ETPT (SEQ ID NO: 1319). 10. The binding protein of claim 9, wherein the FGFR1c binding domain comprises one or more of: (SEQ ID NO: 109)CGAGLFTCRS TNICISQVWV CDGVDDCEDN SDEDSC;(SEQ ID NO: 110)CGAGLFTCRS TNICISQAWV CDGVDDCEDN SDENYC;(SEQ ID NO: 111)CGAGLFTCRS TNICISQAWV CDGVDDCEDN SDETNC;(SEQ ID NO: 112)CGEGLFTCGS TNICISSAWV CDGVDDCEDN SDENNC;(SEQ ID NO: 113)CGEGLFTCRS TNICISHAWV CDGVDDCEDN SDENNC;(SEQ ID NO: 114)CGEGLFTCRS TNICISEAWI CDGVDDCEDN SDEKNC;(SEQ ID NO: 115)CGAGLFTCRS AKICISHAWV CDGIDDCEDN SDENNC;(SEQ ID NO: 116)CGAGLFTCRN SKICISQAWV CDGVDDCDDN SDEKYC;(SEQ ID NO: 117)CGASLFTCRR SNICISQAWV CDGVDDCEDN SDEMNC;and(SEQ ID NO: 118)CGAGLFTCRS TKICISQAWV CDGVDDCEDN SDEKNC. 11. The binding protein of claim 10, wherein the FGFR1c binding domain further comprises a linker comprising the sequence SAPASEPPGSL.(SEQ ID NO: 12) 12. The binding protein of claim 11, wherein the FGFR1c binding domain comprises one or more of: (SEQ ID NO: 293)CGAGLFTCRSTNICISQVWVCDGVDDCEDNSDEDSCSAPASEPPGSL;(SEQ ID NO: 294)CGAGLFTCRSTNICISQAWVCDGVDDCEDNSDENYCSAPASEPPGSL;(SEQ ID NO: 295)CGAGLFTCRSTNICISQAWVCDGVDDCEDNSDETNCSAPASEPPGSL;(SEQ ID NO: 448)CGEGLFTCGSTNICISSAWVCDGVDDCEDNSDENNCSAPASEPPGSL;(SEQ ID NO: 297)CGEGLFTCRSTNICISHAWVCDGVDDCEDNSDENNCSAPASEPPGSL;(SEQ ID NO: 449)CGEGLFTCRSTNICISEAWICDGVDDCEDNSDEKNCSAPASEPPGSL;(SEQ ID NO: 450)CGAGLFTCRSAKICISHAWVCDGIDDCEDNSDENNCSAPASEPPGSL;(SEQ ID NO: 464)CGAGLFTCRNSKICISQAWVCDGVDDCDDNSDEKYCSAPASEPPGSL;(SEQ ID NO: 296)CGASLFTCRRSNICISQAWVCDGVDDCEDNSDEMNCSAPASEPPGSL;and(SEQ ID NO: 287)CGAGLFTCRSTKICISQAWVCDGVDDCEDNSDEKNCSAPASEPPGSL. 13. The binding protein of claim 12, wherein the FGFR1c binding domain comprises: (SEQ ID NO: 297)CGEGLFTCRSTNICISHAWVCDGVDDCEDNSDENNCSAPASEPPGSL. 14. The binding protein of claim 7, wherein the linker of (c) comprises one or more of: AQPT (SEQ ID NO:1322), AHT, PERT (SEQ ID NO: 7), TTRT (SEQ ID NO: 8), GTTGPT (SEQ ID NO: 9), ETSGPT (SEQ ID NO: 10), SQDPEFHKVS (SEQ ID NO: 11), SAPASEPPGSL (SEQ ID NO: 12), GRPGPGATSAPAA (SEQ ID NO: 13), and GDSHILPFSTPGPST (SEQ ID NO: 14). 15. A binding protein comprising the sequence: (SEQ ID NO 359)CGADQFRCGNGSCVPRAWRCDGVDDCGDGSDEAPEICETPTCQSNEFRCRSGRCIPQHWLCDGLNDCGDGSDESQQCSAPASEPPGSLCGEGLFTCRSTNICISHAWVCDGVDDCEDNSDENNCSAPASEPPGSL. 16. The binding protein of claim 1 or 7, wherein the binding protein further comprises a half life-extending moiety that increases the serum half-life of the binding protein in a mammal compared to the serum half-life of the binding protein lacking the half life-extending moiety in a mammal. 17. The binding protein of claim 16, wherein the half life-extending moiety is one or more of: polyethylene glycol (PEG), human serum albumin (HSA), an immunoglobulin (IgG), and an Fc moeity. 18. The binding protein of claim 16, wherein the half life-extending moiety comprises a protein sequence that specifically binds a blood factor. 19. The binding protein of claim 18, wherein the blood factor is serum albumin, an immunoglobulin or an erythrocyte. 20. The binding protein of claim 1 or 7, wherein the binding protein comprises an amino acid sequence comprising one or more non-naturally occurring amino acids. 21. A binding protein that selectively binds β-Klotho and FGFR1c comprising (a) one or more domains that selectively bind β-Klotho, and (b) one or more domains that selectively bind FGFR1c, wherein the binding protein comprises: (a) a β-Klotho binding domain comprising one or more of: (SEQ ID NO: 254)C[AGP][APS][DGN][EQ]F[QRT]C[GNRS][GNS][GT][GKQS][IK]C[ILV]P[LQRV][AEHP]W[LRV]CDG[DLV][DN]DCGD[GN]SDE[AEKPS][GLPS][-AEV][-IT]C;(SEQ ID NO: 597)CLPDEFQC[SG]SGRCIPQ[HT]W[VL]CDGLNDCGDGSDE[PS]PA[HT]C;(SEQ ID NO: 249)C[AGPR][AP][DGNS][EQ]F[QRT]C[GSK]N[GT][GHR][-R]C[ILV][PS][ALQ][NST]W[LRV]CDG[DEV]DDC[GL]DGSDE[AET][DNS][-A][-T]C,and wherein the β-Klotho binding domain retains the ability to bind β-Klotho;(b) an FGFR1c binding domain comprising: (SEQ ID NO: 297)CGEGLFTCRSTNICISHAWVCDGVDDCEDNSDENNCSAPASEPPGSL; andwherein amino acids in brackets indicate alternative amino acids at a specified position and “−” indicates no amino acid at the specified position. 22. The binding protein of claim 21, further comprising at least one linker joining (a) and (b). 23. The binding protein of claim 22, wherein the linker comprises SAPASEPPGSL (SEQ ID NO:12). 24. The binding protein of claim 23, wherein the β-Klotho binding domain of (a) comprises one or more of: (SEQ ID NO: 255)CGPDQFRCSSGKCIPQHWLCDGLNDCGDGSDESPATC;(SEQ ID NO: 256)CGANEFQCRSTGICVPVEWVCDGDNDCGDGSDEPPVC;(SEQ ID NO: 257)CGADQFRCGNGSCVPRAWRCDGVDDCGDGSDEAPEIC;(SEQ ID NO: 258)CGPDEFRCNNGQCIPLPWRCDGVDDCGDNSDEPLEIC;(SEQ ID NO: 259)CASGEFTCNNGQCVPLAWRCDGVNDCQDGSDEKGC;(SEQ ID NO: 260)CGPDEFRCNNGQCIPLPWRCDGVDDCGDNSDEPLEIC;(SEQ ID NO: 261)CPPDEFQCRGTKKCLPLAWVCDGDNDCEDDSDEESC;(SEQ ID NO: 1237)CLPDEFQCGSGRCIPQHWLCDGLNDCGDGSDEPPAHC;(SEQ ID NO: 1326)CLPDEFQCGSGRCIPQHWLCDGLNDCGDGSDEPPAHC;(SEQ ID NO: 1327)CAPGEFTCKNTGRCIPLNWRCDGDDDCGDGSDETDC;and(SEQ ID NO: 1328)CGPDEFRCNNGQCIPLPWRCDGVDDCGDNSDEPLEIC. 25. A binding protein that selectively binds β-Klotho and FGFR1c comprising (a) one or more domains that selectively bind β-Klotho, and (b) one or more domains that selectively bind FGFR1c, wherein the binding protein comprises: (a) a β-Klotho binding domain comprising: (i) a first binding domain comprising one or more of: (SEQ ID NO: 254)C[AGP][APS][DGN][EQ]F[QRT]C[GNRS][GNS][GT][GKQS][-IK]C[ILV]P[LQRV][AEHP]W[LRV]CDG[DLV][DN]DCGD[GN]SDE[AEKPS][GLPS][-AEV][-IT]C;(SEQ ID NO: 597)CLPDEFQC[SG]SGRCIPQ[HT]W[VL]CDGLNDCGDGSDE[PS]PA[HT]C;(SEQ ID NO: 249)C[AGPR][AP][DGNS][EQ]F[QRT]C[GSK]N[GT][GHR][-R]C[ILV][PS][ALQ][NST]W[LRV]CDG[DEV]DDC[GL]DGSDE[AET][DNS][-A][-T]C, wherein the first binding domain retains the ability to bind β-Klotho;(ii) a second binding domain comprising one or more of: (SEQ ID NO: 394)CQSNEFRCRSGRCIPQHWLCDGLNDCGDGSDE[PS][PQ][AQ][-H]C;(SEQ ID NO: 217)C[ELPQR][APS][DGIN][EGQ][FQ][FKPQRT][-E]C[GNRS][NS]G[HNQR]C[IV]P[AELPQRV][AHPQRT]W[LRV]CDG[DEV][DNP]DC[GLQ]D[DGNS]SDE[AEKT][DGLNS][-A][-H]C;(SEQ ID NO: 254)C[AGP][APS][DGN][EQ]F[QRT]C[GNRS][GNS][GT][GKQS][-IK]C[ILV]P[LQRV][AEHP]W[LRV]CDG[DLV][DN]DCGD[GN]SDE[AEKPS][GLPS][-AEV][-IT]C; (SEQ ID NO: 481)CQSNEFRCRSGRCIPQHWLCDGLNDCGDGSDESQQCSAPASEPPGSL, wherein the second binding domain retains the ability to bind β-Klotho; and(iii) a linker joining the first binding domain and the second binding domain; and(b) an FGFR1c binding domain comprising (SEQ ID NO: 297)CGEGLFTCRSTNICISHAWVCDGVDDCEDNSDENNCSAPASEPPGSL; and(c) a linker joining the sequences of (a) and (b),wherein amino acids in brackets indicate alternative amino acids at a specified position and “−” indicates no amino acid at the specified position. 26. The binding protein of claim 25, wherein the second binding domain of (a) comprises one or more of: (SEQ ID NO: 481)CQSNEFRCRSGRCIPQHWLCDGLNDCGDGSDESQQCSAPASEPPGSL;(SEQ ID NO: 159)CQSNEFRCRSGRCIPQHWLCDGLNDCGDGSDESQQC;(SEQ ID NO: 1323)CRAGEFRCSNGRCVPLTWLCDGEDDCQDNSDEKNC;(SEQ ID NO: 1324)CPSNQFPCRSTGICIPLAWVCDGLNDCGDGSDESPAHC;and(SEQ ID NO: 1325)CQSNEFRCRSGRCIPQHWLCDGLNDCGDGSDEPPAHC. 27. The binding protein of claim 26, wherein the linker of (a) comprises ETPT (SEQ IP NO: 1319). 28. The binding protein of claim 27, wherein the first b-Klotho binding domain comprises: (SEQ ID NO: 481)CQSNEFRCRSGRCIPQHWLCDGLNDCGDGSDESQQCSAPASEPPGSL. 29. A pharmaceutical composition comprising: (a) a binding protein of claim 1, 7, 21 or 25, and (b) a pharmaceutically acceptable formulation agent. 30. The pharmaceutical composition of claim 29, wherein the pharmaceutically acceptable formulation agent is a carrier, adjuvant, solubilizer, stabilizer, or anti-oxidant. 31. The binding protein of claim 1, 7, 21 or 25, wherein the β-Klotho binding domain of (a) comprises SEQ ID NO:312.
연구과제 타임라인
LOADING...
LOADING...
LOADING...
LOADING...
LOADING...
이 특허에 인용된 특허 (70)
Yayon,Avner; Rom,Eran; Thomassen Wolf,Elisabeth; Borges,Eric, Antibodies that block receptor protein tyrosine kinase activation, methods of screening for and uses thereof.
Kim Jin-Seok (Salt Lake City UT) Maruyama Atsushi (Yokohama JPX) Akaike Toshihiro (Tokyo JPX) Kim Sung Wan (Salt Lake City UT), Cationic polymer and lipoprotein-containing system for gene delivery.
Keifer, Michael C.; Valenzuela, Pablo D. T.; Barr, Philip J., Compositions comprising polynucleotides encoding human fibroblast growth factor receptor and uses thereof.
Keifer Michael C. (Clayton CA) Valenzuela Pablo D. T. (Berkeley CA) Barr Philip J. (Oakland CA), Expression and use of human fibroblast growth factor receptor.
Bergonzoni Laura (Milan ITX) Mazue Guy (Milan ITX) Isacchi Antonella (Milan ITX) Roncucci Romeo (Milan ITX) Sarmientos Paolo (Milan ITX), Extracellular form of the human fibroblast growth factor receptor.
Imamura, Toru; Asada, Masahiro; Suzuki, Masashi, Heparin-binding protein modified with heparan sulfate sugar chains, process for producing the same and pharmaceutical compositions containing the same.
Queen Cary L. (Los Altos CA) Co Man Sung (Cupertino CA) Schneider William P. (Mountain View CA) Landolfi Nicholas F. (Milpitas CA) Coelingh Kathleen L. (San Francisco CA) Selick Harold E. (Belmont CA, Humanized immunoglobulins.
Aebischer Patrick (Providence RI) Galletti Pierre M. (Providence RI) Panol George (Warwick RI) Miracoli Luigi (Genoa ITX), Implantable delivery system for biological factors.
Aebischer Patrick (Providence RI) Winn Shelley R. (Providence RI) Galletti Pierre M. (Providence RI), In vivo delivery of neurotransmitters by implanted, encapsulated cells.
Sanford John C. (Geneva NY) Wolf Edward D. (Ithaca NY) Allen Nelson K. (Newfield NY), Method for transporting substances into living cells and tissues and apparatus therefor.
Aslam Muhammed (Rochester NY) Light William (Victor NY), Method of making a projection viewable transparency comprising an electrostatographic toner image.
Roninson Igor B. (818 S. Laflin St. Chicago IL 60607) Holzmayer Tatyana (1451 W. Flournoy St. ; Apt. 2E Chicago IL 60607) Choi Kyunghee (1121 Albion St. ; Apt. 806 Denver CO 80220), Methods and applications for efficient genetic suppressor elements.
Davis Frank F. (19 Farmingdale Rd. East Brunswick NJ 08816) Van Es Theodorus (313 Overbrook Rd. Piscataway NJ 08854) Palczuk Nicholas C. (45 W. Franklin St. Bound Brook NJ 08805), Non-immunogenic polypeptides.
Benjamin Howard ; Chai Ling ; Findeis Mark A. ; Goodwin William ; Hundal Arvind ; Israel David I. ; Kelley Michael ; Keough Martin P. ; Lu Kuanghui ; Natoli Farah ; Peticolas Alicia ; Signer Ethan R., Peptide compounds useful for modulating FGF receptor activity.
Surani Azim M. (Cambridge GB3) Neuberger Michael S. (Cambridge GB3) Bruggemann Marianne (Cambridge GB3), Production of antibodies from transgenic animals.
Vegeto Elisabetta (7707 Eads Ave. LaJolla CA 92037) McDonnell Donald P. (10382 Rue Riviere Verte San Diego CA 92131) O\Malley Bert W. (629 Ramblewood Houston TX 77079), Progesterone receptor having C. terminal hormone binding domain truncations.
Cabilly Shmuel (Monrovia CA) Heyneker Herbert L. (Burlingame CA) Holmes William E. (Pacifica CA) Riggs Arthur D. (La Verne CA) Wetzel Ronald B. (San Francisco CA), Recombinant immunoglobin preparations.
Bujard Hermann (Heidelberg DEX) Gossen Manfred (Heidelberg DEX) Salfeld Jochen G. (North Grafton MA) Voss Jeffrey W. (Framingham MA), Tight control of gene expression in eucaryotic cells by tetracycline-responsive promoters.
※ AI-Helper는 부적절한 답변을 할 수 있습니다.