US2013274447A1PendingUtilityA1
Humanized antibodies against cxcr3
Assignee: TEVA BIOPHARMACEUTICALS USA INCPriority: Feb 1, 2007Filed: Apr 5, 2013Published: Oct 17, 2013
Est. expiryFeb 1, 2027(~0.5 yrs left)· nominal 20-yr term from priority
A61P 35/00A61P 35/02A61P 37/06A61P 37/00A61P 25/00A61P 29/00C07K 2317/24C07K 2317/565A61P 19/02C07K 2317/92C07K 16/2866A61P 17/06C07K 2317/56A61P 11/00A61P 1/04A61K 39/395C07K 16/28
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Claims
Abstract
Disclosed are humanized antibodies that bind specifically to the receptor CXCR3. The humanized antibodies may be antagonists and may be used to treat or diagnose conditions associated with CXCR3 function.
Claims
exact text as granted — not AI-modified1 .- 98 . (canceled)
99 . A humanized antibody heavy chain variable region comprising:
(a) a CDR-H1 comprising the amino acid sequence {N,S,Y}MAS; (b) a CDR-H2 comprising the amino acid sequence {T,A,Y}I{S,Y}{S,G,T,Y}{G,S}{G,Y}G{F,S,Y}TYY{P,A}DS{L,Y,V}KG; and (c) a CDR-H3 comprising the amino acid sequence {H,Y}{G,Y}{A,Y}PM{T,Y}T{V,Y}ITY{A,Y}PYYFYY.
100 . The humanized antibody heavy chain variable region of claim 99 , comprising the amino acid sequence:
EVQLLESGGGLVQPGGSLRLSCAASGFTFS{ N , S , Y } YAMS WVRQAPGKGLEWVS{ T , A , Y }
I { S , Y }{ S , G , T , Y }{ G , S }{ G , Y } G { F , S , Y } TYY { P , A } DS { L , Y , V } KG RFTISRDNSKNTLYLQMNSL
RAEDTAVYYCAK{ H , Y }{ G , Y }{ A , Y } PM { T , Y } T { V , Y } ITY { A , Y } PYYFYY WGQGTTVTVSS.
101 . A polynucleotide according to claim 99 , wherein the polynucleotide encodes a polypeptide comprising a humanized antibody heavy chain variable region comprising:
(a) a CDR-H1 comprising an amino acid sequence selected from the group consisting of NYAIS, YYAMS, and NYAMS; (b) a CDR-H2 comprising an amino acid sequence selected from the group consisting of TYSSGGVYTYYRDSLKG, TIYSGGSYTFYPDSLEG, TIYSGGGYTFYLDSLKG, and TISSGGGYTYYPDSLKG; and (c) a CDR-H3 comprising an amino acid sequence selected from the group consisting of HGAPMTTVITYAPYYF{D,Y}Y, HGAPMTTVITYAPYYFYY, HGAPMTTVITYAPYYFDY, HGAAMTTVITYAPFYFYY, HGAPMSTEITYAPYYFYY, and HSYPMTTVITYAPYYFYY.
102 . The polynucleotide of claim 101 , wherein the humanized antibody heavy chain variable region comprises the amino acid sequence:
EV{M, Q}L{V, L}ESGGGLV{K, Q}PGGSL{K, R}LSCAASGFTFSNYAMSWVRQ{T, A}P
{E, G}K{R, G}LEWV{A, S}TISSGGGYTYYPDSLKGRFTISRDN{A, S}KNTL{F, Y}LQM{S,
N}SLR{S, A}EDTAVYYC{V, A}{R, K}HGAPMTTVITYAPYYF{D, Y}YWGQGTT{L, V}T
VSS.
103 . The polynucleotide of claim 102 , wherein the humanized antibody heavy chain variable region comprises the amino acid sequence:
(SEQ ID NO: 11)
EVQLLESGGGLVQPGGSLRLSCAASGFTFS NYAMS WVRQAPKGLEWVS TI
SSGGGYTYYPDSLKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK HGA
PMTTVITYAPYYFYY WGQGTTVTVSS.
104 . The polynucleotide of claim 101 , wherein the polynucleotide encodes an amino acid sequence selected from the group consisting of:
(a)
EVQLLESGGGLVQPGGSLRLSCAASGFTFS NYAIS WVRQAPGKGLEWVS
TYSSGGVYTYYRDSLKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK
HGAAMTTVITYAPFYFYY WGQGTTVTVSS;
(b)
EVQLLESGGGLVQPGGSLRLSCAASGFTFS YYAMS WVRQAPGKGLEWVS
TIYSGGSYTFYPDSLEG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK
HGAPMSTEITYAPYYFYY WGQGTTVTVSS;
(c)
EVQLLESGGGLVQPGGSLRLSCAASGFTFS NYYMS WVRQAPGKGLEWVS
TIYSGGGYTFYLDSLKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK
HSYPMTTVITYAPYYFYY WGQGTTVTVSS;
(d)
EVQLLESGGGLVQPGGSLRLSCAASGFTFS NYAMS WVRQAPGKGLEWVS
TISSGGGYTYYPDSLKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK
HGAPMTTVITYAPYYFYY WGQGTTVTVSS;
and
(e)
EVQLLESGGGLVQPGGSLRLSCAASGFTFS NYAMS WVRQAPGKGLEWVS
TISSGGGYTYYPDSLKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK
HGAPMTTVITYAPYYFYY WGQGTTVTVSS.
105 . A polynucleotide encoding a polypeptide comprising a humanized antibody light chain variable region comprising:
(a) a CDR-L1 comprising the amino acid sequence: RAS{S,Q}SV{K,S}SY{M,L}{Y,A}; (b) a CDR-L2 comprising the amino acid sequence: {Y,D}{T,A}SN{L,R}A{P,T}; and (c) a CDR-L3 comprising the amino acid sequence {Q,Y}Q{F,Y}TT{S,Y}PYT.
106 . The polynucleotide of claim 105 , wherein the humanized antibody light chain variable region comprises an amino acid sequence selected from the group consisting of:
(a)
{E, D}{N, V}V{L, M}TQSPAFLSVTPGEKVTITC RAS { S , Q } SV { K , S } SY { M , L }{ Y , A }
WYQQKPDQAPKL{W, L}I{Y, K}{ Y , D }{ T , A } SN { L , R } A { P , T }GVPSRFSGSGSG{N, T}D{Y,
F}TFTISSLEAEDAATYYC{ Q , Y } Q { F , Y } TT { S , Y } PYT FGGGTKLEIKR;
and
(b)
EIVLTQSPATLSLSPGERATLSC RAS { S , Q } SV { K , S } SY { M , L }{ Y , A }WYQQKPGQAPRLLIY
{ Y , D }{ T , A } SN { L , R } A { P , T }GIPARFSGSGSGTDFTLTISSLEPEDFAVYYC{ Q , Y } Q { F , Y } TT { S ,
Y } PYT FGGGTKLEIKR
107 . A polynucleotide according to claim 105 , wherein the polynucleotide encodes a polypeptide comprising a humanized antibody light chain variable region comprising:
(a) a CDR-L1 comprising the amino acid sequence RASSSVKYMY; (b) a CDR-L2 comprising the amino acid sequence YTSNLAP; and (c) a CDR-L3 comprising an amino acid sequence selected from the group consisting of QQFTTSPYT, YQFTTSPYT, QQYTTSPYT, and QQFTTYPYT.
108 . The polynucleotide of claim 107 , wherein the humanized antibody light chain variable region comprises the amino acid sequence:
{E, D}{I, N, V}V{L, M}TQSPA{T, F, I}{L, M}S{L, A, V}{S, T}{L, P}GE{R, K}{A, V}T{L, M, I}
{S, T, N}C RASSSVKYMY WYQQK{S, P}{G, D}{Q, A}{A, S}P{R, K}L{L, W}I{Y, K} YTSNLAP
G{I, V}P{A, S}RFSGSGSG{T, N}{D, S}{F, Y}{T, S}{L, F}TISS{M, L}E{A, G, P}ED{F, A}A
{V, T}YYC{ Q , Y } QFTT { S , Y } PYT FGGGTKLEIKR.
109 . The polynucleotide of claim 107 , wherein the humanized antibody light chain variable region comprises an amino acid sequence selected from the group consisting of
(a)
EINVLTQSPATLSLSLGERATLSC RASSSVKYMY WYQQKSGQAPRLLIY YTSNLAP GIPA
RFSGSGSGTDFTLTISSMEAEDFAVYYC QQFTTSPYT FGGGTKLEIKR;
(b)
ENVLTQSPAFLSVTPGEKVTITC RASSSVKYMY WYQQKPDQAPKLWIY YTSNLAP GVPS
RFSGSGSGNDYTFTISSLEAEDAATYYC QQFTTSPYT FGGGTKLEIKR;
(c)
EIVLTQSPATLSLSLGERATLSC RASSSVKYMY WYQQKSGQAPRLLIY YTSNLAP GIPARF
SGSGSGTDFTLTISSMEAEDFAVYYC QQFTTSPYT FGGGTKLEIKR;
(d)
EIVLTQSPATLSLSPGERATLSC RASSSVKYMY WYQQKPGQAPRLLIY YTSNLAP GIPARF
SGSGSGTDFTLTISSLEPEDFAVYYC QQFTTSPYT FGGGTKLEIKR;
(e)
EIVLTQSPATLSLSPGERATLSC RASSSVKYMY WYQQKPGQAPRLLIY YTSNLAP GIPARF
SGSGSGTDFTLTISSLEPEDFAVYYC YQFTTSPYT FGGGTKLEIKR;
(f)
EIVLTQSPATLSLSPGERATLSC RASSSVKYMY WYQQKPGQAPRLLIY YTSNLAP GIPARF
SGSGSGTDFTLTISSLEPEDFAVYYC QQYTTSPYT FGGGTKLEIKR);
(g)
EIVLTQSPATLSLSPGERATLSC RASSSVKYMY WYQQKPGQAPRLLIY YTSNLAP GIPARF
SGSGSGTDFTLTISSLEPEDFAVYYC QQFTTYPYT FGGGTKLEIKR;
and
(h)
ENVLTQSPAFLSVTPGEKVTITC RASSSVKYMY WYQQKPDQAPKLWIY YTSNLAP GVPS
RFSGSGSGNDYTFTISSLEAEDAATYYC QQFTTSPYT FGGGTKLEIKR.
110 . A polynucleotide encoding a polypeptide comprising:
(a) a humanized antibody heavy chain variable region comprising:
(1) a CDR-H1 comprising the amino acid sequence NYMAS;
(2) a CDR-H2 comprising the amino acid sequence TISSGGGYTYYPDSLKG; and
(3) a CDR-H3 comprising an amino acid sequence selected from the group consisting of HGAPMTTVITYAPYYF{D,Y}Y), HGAPMTTVITYAPYYFYY, and HGAPMTTVITYAPYYFDY; and
(b) a humanized antibody light chain variable region comprising:
(1) a CDR-L1 comprising the amino acid sequence RASSSVKYMY;
(2) a CDR-L2 comprising the amino acid sequence YTSNLAP; and
(3) a CDR-L3 comprising the amino acid sequence QQFTTSPYT, YQFTTSPYT, and QQYTTSPYT.
111 . The polynucleotide of claim 110 , wherein:
(a) the CDR-H1 comprises the amino acid sequence NYMAS; (b) the CDR-H2 comprises the amino acid sequence TISSGGGYTYYPDSLKG; (c) the CDR-H3 comprises the amino acid sequence HGAPMTTVITYAPYYF{D,Y}Y; (d) the CDR-L1 comprises the amino acid sequence RASSSVKYMY; (e) the CDR-L2 comprises the amino acid sequence YTSNLAP; and (f) the CDR-L3 comprises the amino acid sequence QQFTTSPYT.
112 . A recombinant polynucleotide comprising a promoter sequence operably linked to the polynucleotide of claim 110 .
113 . An isolated cell transformed with the polynucleotide of claim 112 .
114 . A polynucleotide according to claim 110 , wherein the polypeptide comprises:
(a) a humanized heavy chain variable region comprising the amino acid sequence:
EVQLLESGGGLVQPGGSLRLSCAASGFTFS NYAMS WVRQAPGKGLEWVS T
ISSGGGYTYYPDSLKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK HG
APMTTVITYAPYYFYY WGQGTTVTVSS;
and
(b) a humanized light chain variable region comprising the amino acid sequence
EIVLTQSPATLSLSLGERATLSC RASSSVKYMY WYQQKSGQAPRLLIY YTSNLAP GIPARF
SGSGSGTDFTLTISSMEAEDFAVYYC QQFTTSPYT FGGGTKLEIKR.
115 . A polynucleotide according to claim 110 , wherein the polypeptide comprises:
(a) a humanized heavy chain variable region comprising the amino acid sequence:
EVQLLESGGGLVQPGGSLRLSCAASGFTFS NYAMS WVRQAPGKGLEWVS T
ISSGGGYTYYPDSLKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK HG
APMTTVITYAPYYFYY WGQGTTVTVSS;
and
(b) a humanized light chain variable region comprising the amino acid sequence:
ENVLTQSPAFLSVTPGEKVTITC RASSSVKYMY WYQQKPDQAPKLWIY YT
SNLAP GVPSRFSGSGSGNDYTFTISSLEAEDAATYYC QQFTTSPYT FGGG
TKLEIKR.
116 . A polynucleotide according to claim 110 , wherein the polypeptide comprises:
(a) a humanized heavy chain variable region comprising the amino acid sequence:
EVQLLESGGGLVQPGGSLRLSCAASGFTFS NYAMS WVRQAPGKGLEWVS T
ISSGGGYTYYPDSLKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK HG
APMTTVITYAPYYFYY WGQGTTVTVSS;
and
(b) a humanized light chain variable region comprising the amino acid sequence
EIVLTQSPATLSLSPGERATLSC RASSSVKYMY WYQQKPGQAPRLLIY YTSNLAP GIPARF
SGSGSGTDFTLTISSLEPEDFAVYYC QQFTTSPYT FGGGTKLEIKR.
117 . A polynucleotide according to claim 110 , wherein the polypeptide comprises:
(a) a humanized heavy chain variable region comprising the amino acid sequence:
EVQLLESGGGLVQPGGSLRLSCAASGFTFS NYAMS WVRQAPGKGLEWVS T
ISSGGGYTYYPDSLKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK HG
APMTTVITYAPYYFYY WGQGTTVTVSS;
and
(b) a humanized light chain variable region comprising the amino acid sequence
EIVLTQSPATLSLSPGERATLSC RASSSVKYMY WYQQKPGQAPRLLIY YTSNLAP GIPARF
SGSGSGTDFTLTISSLEPEDFAVYYC YQFTTSPYT FGGGTKLEIKR.
118 . A polynucleotide according to claim 110 , wherein the polypeptide comprises:
(a) a humanized heavy chain variable region comprising the amino acid sequence:
EVQLLESGGGLVQPGGSLRLSCAASGFTFS NYAMS WVRQAPGKGLEWVS T
ISSGGGYTYYPDSLKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK HG
APMTTVITYAPYYFYY WGQGTTVTVSS;
and
(b) a humanized light chain variable region comprising the amino acid sequence
EIVLTQSPATLSLSPGERATLSC RASSSVKYMY WYQQKPGQAPRLLIY YTSNLAP GIPARF
SGSGSGTDFTLTISSLEPEDFAVYYC QQYTTSPYT FGGGTKLEIKR.
119 . A polynucleotide according to claim 110 , wherein the polypeptide comprises:
(a) a humanized heavy chain variable region comprising the amino acid sequence:
EVQLLESGGGLVQPGGSLRLSCAASGFTFS NYAMS WVRQAPGKGLEWVS T
ISSGGGYTYYPDSLKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK HG
APMTTVITYAPYYFYY WGQGTTVTVSS;
and
(b) a humanized light chain variable region comprising the amino acid sequence
EIVLTQSPATLSLSPGERATLSC RASSSVKYMY WYQQKPGQAPRLLIY YTSNLAP GIPARF
SGSGSGTDFTLTISSLEPEDFAVYYC QQFTTYPYT FGGGTKLEIKR.Join the waitlist — get patent alerts
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