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US 2026/0234240 A1Published application
Il-10 receptor antibodies and methods of use thereof
OwnerJedd D WOLCHOK, Taha MERGHOUB +2inventors
InventorsJedd D WOLCHOK, Taha MERGHOUB, Danny Nejad KHALIL, Elizabeth NYAKATURA
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Abstract
The invention is directed to human monoclonal antibodies that bind to Interleukin 10 (IL-10) and methods of use thereof.
Claims95
An isolated monoclonal antibody or fragment thereof that specifically binds to Interleukin-10 (IL-10) or IL-10 receptor, the monoclonal antibody comprising a heavy chain, light chain or a combination thereof.
A nucleic acid encoding a monoclonal antibody, wherein the monoclonal antibody comprises a VH amino acid sequence as indicated below, or a sequence at least 90% identical thereto:
- a.
- EVQLVESGGGLVQPGGSLRLSCAASGFTFSDYYMYWVRQAPGKGLEWVS
- TISDGGSYTYYPDSVKGRFTISRDNAKNNLYLQMNSLRAEDTAVYYCAR
- GYYYGLFTYWGQGTLVTVSS;
- b.
- EVQLVESGGGLVKPGGSLKLSCAASGFTFSDYYMYWVRQTPEKRLEWVA
- TISDGGSYTYYPDSVKGRFTISRDNAKNNLYLQMSSLKSEDTAMFYCAR
- GYYYGLFTYWGQGTLVTVSA;
- c.
- EVQLQQSGPDLVKPGASVRMSCKASGYTFTNYVMHWVKQRPGQGLEWIG
- YISPYNDGTKYNEKFKGKATLTSDKSSSTAYMELNSLTSEDSAVYYCAG
- GDYSYAMDYWGQGTSVTVSS;
- d.
- EVQLQQSGPDLVKPGASVKMSCKASGYTFTHYVMHWVKQKPGQGLEWIG
- YISPYNDGIKYNEKFKGKATLTSDKSSSTAYMELSSLTSEDSAVYYCAG
- GDYSYAMDYWGQGTSVTVSS;
- e.
- EVQLVESGGGLVKPGGSLKLSCAASGFTFSDYYIYWVRQTPEKRLEWVA
- TISDGGSYTYYPDSVKGRFTISRDNAKNNLYLQMSSLKSEDTAMYYCAR
- GYYYGLFTYWGQGTLVTVSA;
- f.
- QVQLKQSGPSLVQPSQSLSITCTVSGFSLTTYGVHWVRQSPGKGLEWLG
- VIWRGGSTDYNAGFMSRLSITKDNSKSQVFFKMNSLQADDTAIYYCAKN
- SYYYGGNYYFDYWGQGTTLTVSS;
- g.
- QVQLKQSGPSLVQPSQSLSINCTVSGFSLTTYGVHWLRQSPGKGLEWLG
- VIWRGGSTDYNAAFMSRLSITKDNSKSQVFFKMNSLQADDTAIYYCAKP
- YYVYGAMDYWGQGTSVTVSS;
- h.
- QVQLQESGPGLVKPSETLSLTCAVSGGSLSSDYWTWIRQPAGKGLEWIG
- RIFATGTTNYNPSLKSRVTMSIDTSKNQFSLKLNSVTAADTAVYYCARD
- DWYFDLWGRGTLVTVSS;
- i.
- QVQLQESGPGLVKPSETLSLTCTVSGGSISSDYWSWIRQPAGKRLEWIG
- RIFTSGSTNYNPSLKSRVTMSVDTSKNQFSLKLNSLTAADTAVYYCARD
- DWYFDLWGRGTLVTVSS;
- j.
- QVQLQESGPGLVKPSETLSLTCTVSGGSISRDYWSWVRQPAGKGLEWIG
- RIFTNGVTNYNPSLKSRVTMSVDTSKTQFSLKLSSVTAADTAVYFCARD
- DWYLDLWGRGTLVTVSS;
- k.
- QVQMKQSGPGLVQPSQSLSITCTVSGFSLTTYGVHWVRQSPGKGLEWLG
- VIWSGGSTYYNAAFISRLSISKDNSKSQVIFKMNSLQVDDTAIYYCARW
- DGYSFYYGMDYWGQGTSVTVSS;
- or
- l.
- QVQLKQSGPGLVQPSQSLSITCTVSGFSLTSYGVHWVRQSPGKGLEWLG
- VIWSGGSTDYNAAFISRLSISKDNSKSQVFFKMNSLQADDTAIYYCARW
- DGDSFYYAMDYWGQGTSVTVSS.
46 more elements
A nucleic acid encoding a monoclonal antibody, wherein the monoclonal antibody comprises a VL amino acid sequence as indicated below, or a sequence at least 90% identical thereto:
- a.
- DIQMTQSPSSLSASVGDRVTITCRASQDVNTGLNWYQQKPGQAPKLLIY
- WASSRQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPYTF
- GQGTKLEIK;
- b.
- DIVMTQSHKFMSTSVGDRVSITCKASQDVNTGVAWYQQKPGQSPKLLIY
- WASTRHTGVPDRFTGSGSGTDYILTISSVQAEDLALYYCQQHYSTPYTF
- GGGTKLEIK;
- c.
- DIQMTQSPASLSVSVGETVTITCRVSENIYSNLAWYHQKQGKSPQLLVY
- AATNLADGVPSRFSGSKSGTQYSLKISSLQSEDFGSYYCQHFWGTLTFG
- AGTKLELK;
- d.
- DIQMTQSPASLSVSVGETVTITCRVSENIYSNLAWYQQKQGKSPQLLVY
- AATNLADGVSSRFSGSVSGTQYSLKINSLQSEDFGSYYCQHFWGTLTFG
- AGTKLELK;
- e.
- DIVMTQSHKFMSTSVGDRVSITCKASQDVSTGVAWYRQKPGRSPKLLIY
- WASTRHTGVPDRFTGSGSGTDYILTISSVQAEDLALYYCQQHYSTPYTF
- GGGTKLEIK;
- f.
- DVVMTQTPFSLPVSLGDQASISCRSSQSLVHSNGNTHLHWYLQKPGQSP
- KLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYFCSQSTH
- VPPTFGGGTKLEIK;
- g.
- DVLMTQTPLSLPVSLGDQASISCRSSESIVHSNGNTYLEWFLQKPGQSP
- KLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSH
- VPLTFGAGTKLEIK;
- h.
- EIVMTQSPATLSVSPGERATLSCRASQSVSNNLAWYQERPGQAPRLLIY
- GASTRTTGIPARFSGSGSGTEFILTISSLQPEDFAIYYCQQYNEWPWTF
- GQGTKVEIK;
- i.
- EIVMTQSPATLSVSPGERATLSCRASQSVSNNLAWYQQKPGQAPRFLIY
- GASTRATGMPARFSGSGSGTEFTLTISSLQSEDFAVYFCQQYNEWPWTF
- GQGTKVEIK;
- j.
- EIVMTQSPATLSVSPGERATLSCRASQSVSNNLAWYQQTPGQAPRFLIY
- GASTGATGIPARFSGSGSGTEFTLTITSLQSEDFAVYFCQQYNDWPWTF
- GQGTKVEIK;
- k.
- QAVVTQESALTTSPGETVTLTCRSSTGAVTTSNYANWVQEKPDHLFTGL
- IGSTNNRAPGVPARFSGSLIGDKAALIITGAQTEDEARYFCALWYSNHL
- VFGGGTKLTVL;
- or
- l.
- QAVVIQESALTTSPGETVTLTCRSSTGAVTTSNYASWVQEKPDHLFIGL
- IGGTNNRAPGVPARFSGSLIGDKAALTITGAQTEDEAIYFCALWYSNHL
- VFGGGTKLTVL.
46 more elements
A nucleic acid encoding a monoclonal antibody, wherein the monoclonal antibody comprises:
- a. a heavy chain with three CDRs comprising the amino acid sequences GFTFSDYY, ISDGGSYT, and ARGYYYGLFTY respectively, and/or a light chain with three CDRs comprising the amino acid sequences QDVNTG, WAS, and QQHYSTPYT respectively;
- b. a heavy chain with three CDRs comprising the amino acid sequences GFTFSDYY, ISDGGSYT, and ARGYYYGLFTY respectively, and/or a light chain with three CDRs comprising the amino acid sequences QDVNTG, WAS, and QQHYSTPYT respectively;
- c. a heavy chain with three CDRs comprising the amino acid sequences GYTFTNYV, ISPYNDGT, and AGGDYSYAMDY respectively, and/or a light chain with three CDRs comprising the amino acid sequences ENIYSN, AAT, and QHFWGTLT respectively;
- d. a heavy chain with three CDRs comprising the amino acid sequences GYTFTHYV, ISPYNDGI, and AGGDYSYAMDY respectively, and/or a light chain with three CDRs comprising the amino acid sequences ENIYSN, AAT, and QHFWGTLT respectively;
- e. a heavy chain with three CDRs comprising the amino acid sequences GFTFSDYY, ISDGGSYT, and ARGYYYGLFTY respectively, and/or a light chain with three CDRs comprising the amino acid sequences QDVSTG, WAS, and QQHYSTPYT respectively;
- f. a heavy chain with three CDRs comprising the amino acid sequences GFSLTTYG, IWRGGST, and AKNSYYYGGNYYFDY respectively, and/or a light chain with three CDRs comprising the amino acid sequences QSLVHSNGNTH, KVS, and SQSTHVPPT respectively;
- g. a heavy chain with three CDRs comprising the amino acid sequences GFSLTTYG, IWRGGST, and AKPYYVYGAMDY respectively, and/or a light chain with three CDRs comprising the amino acid sequences ESIVHSNGNTY, KVS, and FQGSHVPLT respectively;
- h. a heavy chain with three CDRs comprising the amino acid sequences GGSLSSDY, IFATGTT, and ARDDWYFDL respectively, and/or a light chain with three CDRs comprising the amino acid sequences QSVSNN, GAS, and QQYNEWPWT respectively;
- i. a heavy chain with three CDRs comprising the amino acid sequences GGSISSDY, IFTSGST, and ARDDWYFDL respectively, and/or a light chain with three CDRs comprising the amino acid sequences QSVSNN, GAS, and QQYNEWPWT respectively;
- j. a heavy chain with three CDRs comprising the amino acid sequences GGSISRDY, IFTNGVT, and ARDDWYLDL respectively, and/or a light chain with three CDRs comprising the amino acid sequences QSVSNN, GAS, and QQYNDWPWT respectively;
- k. a heavy chain with three CDRs comprising the amino acid sequences GFSLTTYG, IWSGGST, and ARWDGYSFYYGMDY respectively, and/or a light chain with three CDRs comprising the amino acid sequences TGAVTTSNY, STN, and ALWYSNHLV respectively;
- or
- l. a heavy chain with three CDRs comprising the amino acid sequences GFSLTSYG, IWSGGST, and ARWDGDSFYYAMDY respectively, and/or a light chain with three CDRs comprising the amino acid sequences TGAVTTSNY, GTN, and ALWYSNHLV respectively.
10 more elements
A nucleic acid encoding a monoclonal antibody, wherein the monoclonal antibody comprises:
- a. a VH according to the amino acid sequence of EVOLVESGGGLVQPGGSLRLSCAASGFTFSDYYMYWVRQAPGKGLEWV STISDGGSYTYYPDSVKGRFTISRDNAKNNLYLQMNSLRAEDTAVYYCAR GYYYGLFTYWGQGTLVTVSS or a sequence at least 90% identical thereto, and a VL according to the amino acid sequence of DIQMTQSPSSLSASVGDRVTITCRASQDVNTGLNWYQQKPGQAPKLLIYW ASSRQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPYTFGQGT KLEIK or a sequence at least 90% identical thereto;
- b. a VH according to the amino acid sequence of EVOLVESGGGLVKPGGSLKLSCAASGFTFSDYYMYWVRQTPEKRLE WVATISDGGSYTYYPDSVKGRFTISRDNAKNNLYLQMSSLKSEDTAM FYCARGYYYGLFTYWGQGTLVTVSA or a sequence at least 90% identical thereto, and a VL according to the amino acid sequence of DIVMTQSHKFMSTSVGDRVSITCKASQDVNTGVAWYQQKPGQSPKLL IYWASTRHTGVPDRFTGSGSGTDYILTISSVQAEDLALYYCQQHYSTP YTFGGGTKLEIK or a sequence at least 90% identical thereto;
- c. a VH according to the amino acid sequence of EVQLQQSGPDLVKPGASVRMSCKASGYTFTNYVMHWVKQRPGQGLE WIGYISPYNDGTKYNEKFKGKATLTSDKSSSTAYMELNSLTSEDSAVY YCAGGDYSYAMDYWGQGTSVTVSS or a sequence at least 90% identical thereto, and a VL according to the amino acid sequence of DIQMTQSPASLSVSVGETVTITCRVSENIYSNLAWYHQKQGKSPQLLV YAATNLADGVPSRFSGSKSGTQYSLKISSLQSEDFGSYYCQHFWGTLT FGAGTKLELK or a sequence at least 90% identical thereto;
- d. a VH according to the amino acid sequence of EVQLQQSGPDLVKPGASVKMSCKASGYTFTHYVMHWVKQKPGQGL EWIGYISPYNDGIKYNEKFKGKATLTSDKSSSTAYMELSSLTSEDSAVY YCAGGDYSYAMDYWGQGTSVTVSS or a sequence at least 90% identical thereto, and a VL according to the amino acid sequence of DIQMTQSPASLSVSVGETVTITCRVSENIYSNLAWYQQKQGKSPQLLV YAATNLADGVSSRFSGSVSGTQYSLKINSLQSEDFGSYYCQHFWGTLT FGAGTKLELK or a sequence at least 90% identical thereto;
- e. a VH according to the amino acid sequence of EVOLVESGGGLVKPGGSLKLSCAASGFTFSDYYIYWVRQTPEKRLEW VATISDGGSYTYYPDSVKGRFTISRDNAKNNLYLQMSSLKSEDTAMY YCARGYYYGLFTYWGQGTLVTVSA or a sequence at least 90% identical thereto, and a VL according to the amino acid sequence of DIVMTQSHKFMSTSVGDRVSITCKASQDVSTGVAWYRQKPGRSPKLLI YWASTRHTGVPDRFTGSGSGTDYILTISSVQAEDLALYYCQQHYSTPY TFGGGTKLEIK or a sequence at least 90% identical thereto;
- f. a VH according to the amino acid sequence of QVQLKQSGPSLVQPSQSLSITCTVSGFSLTTYGVHWVRQSPGKGLEWL GVIWRGGSTDYNAGFMSRLSITKDNSKSQVFFKMNSLQADDTAIYYC AKNSYYYGGNYYFDYWGQGTTLTVSS or a sequence at least 90% identical thereto, and a VL according to the amino acid sequence of DVVMTQTPFSLPVSLGDQASISCRSSQSLVHSNGNTHLHWYLQKPGQS PKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYFCSQST HVPPTFGGGTKLEIK or a sequence at least 90% identical thereto;
- g. a VH according to the amino acid sequence of QVQLKQSGPSLVQPSQSLSINCTVSGFSLTTYGVHWLRQSPGKGLEWL GVIWRGGSTDYNAAFMSRLSITKDNSKSQVFFKMNSLQADDTAIYYC AKPYYVYGAMDYWGQGTSVTVSS or a sequence at least 90% identical thereto, and a VL according to the amino acid sequence of DVLMTQTPLSLPVSLGDQASISCRSSESIVHSNGNTYLEWFLQKPGQSP KLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSH VPLTFGAGTKLEIK or a sequence at least 90% identical thereto;
- h. a VH according to the amino acid sequence of QVQLQESGPGLVKPSETLSLTCAVSGGSLSSDYWTWIRQPAGKGLEWI GRIFATGTTNYNPSLKSRVTMSIDTSKNQFSLKLNSVTAADTAVYYCA RDDWYFDLWGRGTLVTVSS or a sequence at least 90% identical thereto, and a VL according to the amino acid sequence of EIVMTQSPATLSVSPGERATLSCRASQSVSNNLAWYQERPGQAPRLLI YGASTRTTGIPARFSGSGSGTEFILTISSLQPEDFAIYYCQQYNEWPWTF GQGTKVEIK or a sequence at least 90% identical thereto;
- i. a VH according to the amino acid sequence of QVQLQESGPGLVKPSETLSLTCTVSGGSISSDYWSWIRQPAGKRLEWI GRIFTSGSTNYNPSLKSRVTMSVDTSKNQFSLKLNSLTAADTAVYYCA RDDWYFDLWGRGTLVTVSS or a sequence at least 90% identical thereto, and a VL according to the amino acid sequence of EIVMTQSPATLSVSPGERATLSCRASQSVSNNLAWYQQKPGQAPRFLI YGASTRATGMPARFSGSGSGTEFTLTISSLQSEDFAVYFCQQYNEWPW TFGQGTKVEIK or a sequence at least 90% identical thereto;
- j. a VH according to the amino acid sequence of QVQLQESGPGLVKPSETLSLTCTVSGGSISRDYWSWVRQPAGKGLEWI GRIFTNGVTNYNPSLKSRVTMSVDTSKTQFSLKLSSVTAADTAVYFCA RDDWYLDLWGRGTLVTVSS or a sequence at least 90% identical thereto, and a VL according to the amino acid sequence of EIVMTQSPATLSVSPGERATLSCRASQSVSNNLAWYQQTPGQAPRFLI YGASTGATGIPARFSGSGSGTEFTLTITSLQSEDFAVYFCQQYNDWPW TFGQGTKVEIK or a sequence at least 90% identical thereto;
- k. a VH according to the amino acid sequence of QVQMKQSGPGLVQPSQSLSITCTVSGFSLTTYGVHWVRQSPGKGLEW LGVIWSGGSTYYNAAFISRLSISKDNSKSQVIFKMNSLQVDDTAIYYCA RWDGYSFYYGMDYWGQGTSVTVSS or a sequence at least 90% identical thereto, and a VL according to the amino acid sequence of QAVVTQESALTTSPGETVTLTCRSSTGAVTTSNYANWVQEKPDHLFT GLIGSTNNRAPGVPARFSGSLIGDKAALIITGAQTEDEARYFCALWYSN HLVFGGGTKLTVL or a sequence at least 90% identical thereto;
- or
- l. a VH according to the amino acid sequence of QVQLKQSGPGLVQPSQSLSITCTVSGFSLTSYGVHWVRQSPGKGLEWL GVIWSGGSTDYNAAFISRLSISKDNSKSQVFFKMNSLQADDTAIYYCA RWDGDSFYYAMDYWGQGTSVTVSS or a sequence at least 90% identical thereto, and a VL according to the amino acid sequence of QAVVIQESALTTSPGETVTLTCRSSTGAVTTSNYASWVQEKPDHLFIGL IGGTNNRAPGVPARFSGSLIGDKAALTITGAQTEDEAIYFCALWYSNHL VFGGGTKLTVL or a sequence at least 90% identical thereto.
10 more elements
A pharmaceutical composition comprising one or more compositions as described herein, and a pharmaceutically acceptable carrier or excipient.
A nanoparticle, wherein the nanoparticles comprise:
- (a) a CD40 agonist antibody, (b) an antibody specific for IL-10 or IL-10R, and (c) monophosphoryl lipid A (MPL).
An engineered cell comprising a chimeric antigen receptor, wherein the chimeric antigen receptor comprises an extracellular ligand binding domain that is specific for Interleukin-10 (IL-10) or IL-10R.
The method of 67, wherein the solid tumor comprises a melanoma, a breast tumor, a lung tumor, a small cell lung cancer tumor, a prostate tumor, an ovarian tumor, a sarcoma, hepatocellular carcinoma, a rectal tumor, a pancreatic tumor, a liver tumor, a biliary tract tumor, or a colon tumor.
The method of 80, wherein the solid tumor comprises a melanoma, a breast tumor, a lung tumor, a small cell lung cancer tumor, a prostate tumor, an ovarian tumor, a sarcoma, hepatocellular carcinoma, a rectal tumor, a pancreatic tumor, a liver tumor, a biliary tract tumor, or a colon tumor.
The method of 86, wherein the solid tumor comprises a melanoma, a breast tumor, a lung tumor, a small cell lung cancer tumor, a prostate tumor, an ovarian tumor, a sarcoma, hepatocellular carcinoma, a rectal tumor, a pancreatic tumor, a liver tumor, a biliary tract tumor, or a colon tumor.
Dependencies are inferred from the claim text.