Dual variable domain immunoglobulin and uses thereof
First Claim
Patent Images
1. A binding protein comprising four polypeptide chains, wherein two polypeptide chains comprise VD1-(X1)n-VD2-C-(X2)n, wherein VD1 is a first heavy chain variable domain, VD2 is a second heavy chain variable domain, C is a heavy chain constant domain, X1 is a linker with the proviso that it is not CH1, and X2 is an Fc region;
- and two polypeptide chains comprise VD1-(X1)n-VD2-C-(X2)n, wherein VD1 is a first light chain variable domain, VD2 is a second light chain variable domain, C is a light chain constant domain, X1 is a linker with the proviso that it is not CH1, and X2 does not comprise an Fc region; and
n is 0 or 1;
wherein said four polypeptide chains of said binding protein form four functional antigen binding sites.
2 Assignments
0 Petitions
Reexamination
Accused Products
Abstract
The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases.
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Citations
43 Claims
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1. A binding protein comprising four polypeptide chains, wherein two polypeptide chains comprise VD1-(X1)n-VD2-C-(X2)n, wherein VD1 is a first heavy chain variable domain, VD2 is a second heavy chain variable domain, C is a heavy chain constant domain, X1 is a linker with the proviso that it is not CH1, and X2 is an Fc region;
- and two polypeptide chains comprise VD1-(X1)n-VD2-C-(X2)n, wherein VD1 is a first light chain variable domain, VD2 is a second light chain variable domain, C is a light chain constant domain, X1 is a linker with the proviso that it is not CH1, and X2 does not comprise an Fc region; and
n is 0 or 1;
wherein said four polypeptide chains of said binding protein form four functional antigen binding sites. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43)
-
2. The binding protein according to claim 1, wherein said binding protein is capable of binding one or more targets.
-
3. The binding protein according to claim 2, wherein said one or more targets is selected from the group consisting of ABCF1;
- ACVR1;
ACVR1B;
ACVR2;
ACVR2B;
ACVRL1;
ADORA2A;
Aggrecan;
AGR2;
AICDA;
AIF1;
AIG1;
AKAP1;
AKAP2;
AMH;
AMHR2;
ANGPT1;
ANGPT2;
ANGPTL3;
ANGPTL4;
ANPEP;
APC;
APOC1;
AR;
AZGP1 (zinc-a-glycoprotein);
B7.1;
B7.2;
BAD;
BAFF;
BAG1;
BAI1;
BCL2;
BCL6;
BDNF;
BLNK;
BLR1 (MDR15);
BlyS;
BMP1;
BMP2;
BMP3B (GDF10);
BMP4;
BMP6;
BMP8;
BMPR1A;
BMPR1B;
BMPR2;
BPAG1 (plectin);
BRCA1;
C19orf10 (IL27w);
C3;
C4A;
C5;
C5R1;
CANT1;
CASP1;
CASP4;
CAV1;
CCBP2 (D6/JAB61);
CCL1 (1-309);
CCL11 (eotaxin);
CCL13 (MCP-4);
CCL15 (MIP-1d);
CCL16 (HCC-4);
CCL17 (TARC);
CCL18 (PARC);
CCL19 (MIP-3b);
CCL2 (MCP-1);
MCAF;
CCL20 (MIP-3a);
CCL21 (MIP-2);
SLC;
exodus-2;
CCL22 (MDC/STC-1);
CCL23 (MPIF-1);
CCL24 (MPIF-2/eotaxin-2);
CCL25 (TECK);
CCL26 (eotaxin-3);
CCL27 (CTACK/ILC);
CCL28;
CCL3 (MIP-1a);
CCL4 (MIP-1b);
CCL5 (RANTES);
CCL7 (MCP-3);
CCL8 (mcp-2);
CCNA1;
CCNA2;
CCND1;
CCNE1;
CCNE2;
CCR1 (CKR1/HM145);
CCR2 (mcp-1RB/RA);
CCR3 (CKR3/CMKBR3);
CCR4;
CCR5 (CMKBR5/ChemR13);
CCR6 (CMKBR6/CKR-L3/STRL22/DRY6);
CCR7 (CKR7/EBI1);
CCR8 (CMKBR8/TER1/CKR-L1);
CCR9 (GPR-9-6);
CCRL1 (VSHK1);
CCRL2 (L-CCR);
CD164;
CD19;
CD1C;
CD20;
CD200;
CD-22;
CD24;
CD28;
CD3;
CD37;
CD38;
CD3E;
CD3G;
CD3Z;
CD4;
CD40;
CD40L;
CD44;
CD45RB;
CD52;
CD69;
CD72;
CD74;
CD79A;
CD79B;
CD8;
CD80;
CD81;
CD83;
CD86;
CDH1 (E-cadherin);
CDH10;
CDH12;
CDH13;
CDH18;
CDH19;
CDH20;
CDH5;
CDH7;
CDH8;
CDH9;
CDK2;
CDK3;
CDK4;
CDK5;
CDK6;
CDK7;
CDK9;
CDKN1A (p21Wap1/Cip1);
CDKN1B (p27Kip1);
CDKN1C;
CDKN2A (p16INK4a);
CDKN2B;
CDKN2C;
CDKN3;
CEBPB;
CER1;
CHGA;
CHGB;
Chitinase;
CHST10;
CKLFSF2;
CKLFSF3;
CKLFSF4;
CKLFSF5;
CKLFSF6;
CKLFSF7;
CKLFSF8;
CLDN3;
CLDN7 (claudin-7);
CLN3;
CLU (clusterin);
CMKLR1;
CMKOR1 (RDC1);
CNR1;
COL18A1;
COL1A1;
COL4A3;
COL6A1;
CR2;
CRP;
CSF1 (M-CSF);
CSF2 (GM-CSF);
CSF3 (GCSF);
CTLA4;
CTNNB1 (b-catenin);
CTSB (cathepsin B);
CX3CL1 (SCYD1);
CX3CR1 (V28);
CXCL1 (GRO1);
CXCL10(IP-10);
CXCL11 (I-TAC/IP-9);
CXCL12 (SDF1);
CXCL13;
CXCL14;
CXCL16;
CXCL2 (GRO2);
CXCL3 (GRO3);
CXCL5 (ENA-78/LIX);
CXCL6 (GCP-2);
CXCL9 (MIG);
CXCR3 (GPR9/CKR-L2);
CXCR4;
CXCR6 (TYMSTR/STRL33/Bonzo);
CYB5;
CYC1;
CYSLTR1;
DAB2IP;
DES;
DKFZp451J0118;
DNCL1;
DPP4;
E2F1;
ECGF1;
EDG1;
EFNA1;
EFNA3;
EFNB2;
EGF;
EGFR;
ELAC2;
ENG;
ENO1;
ENO2;
ENO3;
EPHB4;
EPO;
ERBB2 (Her-2);
EREG;
ERK8;
ESR1;
ESR2;
F3 (TF);
FADD;
FasL;
FASN;
FCER1A;
FCER2;
FCGR3A;
FGF;
FGF1 (aFGF);
FGF10;
FGF11;
FGF12;
FGF12B;
FGF13;
FGF14;
FGF16;
FGF17;
FGF18;
FGF19;
FGF2 (bFGF);
FGF20;
FGF21;
FGF22;
FGF23;
FGF3 (int-2);
FGF4 (HST);
FGF5;
FGF6 (HST-2);
FGF7 (KGF);
FGF8;
FGF9;
FGFR3;
FIGF (VEGFD);
FIL1 (EPSILON);
FIL1 (ZETA);
FLJ12584;
FLJ25530;
FLRT1 (fibronectin);
FLT1;
FOS;
FOSL1 (FRA-1);
FY (DARC);
GABRP (GABAa);
GAGEB1;
GAGEC1;
GALNAC4S-6ST;
GATA3;
GDF5;
GFI1;
GGT1;
GM-CSF;
GNAS1;
GNRH1;
GPR2 (CCR10);
GPR31;
GPR44;
GPR81 (FKSG80);
GRCC10 (C10);
GRP;
GSN (Gelsolin);
GSTP1;
HAVCR2;
HDAC4;
HDAC5;
HDAC7A;
HDAC9;
HGF;
HIF1A;
HIP1;
histamine and histamine receptors;
HLA-A;
HLA-DRA;
HM74;
HMOX1;
HUMCYT2A;
ICEBERG;
ICOSL;
ID2;
IFN-a;
IFNA1;
IFNA2;
IFNA4;
IFNA5;
IFNA6;
IFNA7;
IFNB1;
IFNgamma;
IFNW1;
IGBP1;
IGF1;
IGF1R;
IGF2;
IGFBP2;
IGFBP3;
IGFBP6;
IL-1;
IL10;
IL10RA;
IL10RB;
IL11;
IL11RA;
IL-12;
IL12A;
IL12B;
IL12RB1;
IL12RB2;
IL13;
IL13RA1;
IL13RA2;
IL14;
IL15;
IL15RA;
IL16;
IL17;
IL17B;
IL17C;
IL17R;
IL18;
IL18BP;
IL18R1;
IL18RAP;
IL19;
IL1A;
IL1B;
IL1F10;
IL1F5;
IL1F6;
IL1F7;
IL1F8;
IL1F9;
IL1HY1;
IL1R1;
IL1R2;
IL1RAP;
IL1RAPL1;
IL1RAPL2;
IL1RL1;
IL1RL2;
IL1RN;
IL2;
IL20;
IL20RA;
IL21R;
IL22;
IL22R;
IL22RA2;
IL23;
IL24;
IL25;
IL26;
IL27;
IL28A;
IL28B;
IL29;
IL2RA;
IL2RB;
IL2RG;
IL3;
IL30;
IL3RA;
IL4;
IL4R;
IL5;
IL5RA;
IL6;
IL6R;
IL6ST (glycoprotein
130);
IL7;
IL7R;
IL8;
IL8RA;
IL8RB;
IL8RB;
IL9;
IL9R;
ILK;
INHA;
INHBA;
INSL3;
INSL4;
IRAK1;
IRAK2;
ITGA1;
ITGA2;
ITGA3;
ITGA6 (a6 integrin);
ITGAV;
ITGB3;
ITGB4 (b 4 integrin);
JAG1;
JAK1;
JAK3;
JUN;
K6HF;
KAI1;
KDR;
KITLG;
KLF5 (GC Box BP);
KLF6;
KLK10;
KLK12;
KLK13;
KLK14;
KLK15;
KLK3;
KLK4;
KLK5;
KLK6;
KLK9;
KRT1;
KRT19 (Keratin
19);
KRT2A;
KRTHB6 (hair-specific type II keratin);
LAMA5;
LEP (leptin);
Lingo-p75;
Lingo-Troy;
LPS;
LTA (TNF-b);
LTB;
LTB4R (GPR16);
LTB4R2;
LTBR;
MACMARCKS;
MAG or Omgp;
MAP2K7 (c-Jun);
MDK;
MIB1;
midkine;
MIF;
MIP-2;
MKI67 (Ki-67);
MMP2;
MMP9;
MS4A1;
MSMB;
MT3 (metallothionectin-III);
MTSS1;
MUC1 (mucin);
MYC;
MYD88;
NCK2;
neurocan;
NFKB1;
NFKB2;
NGFB (NGF);
NGFR;
NgR-Lingo;
NgR-Nogo66 (Nogo);
NgR-p75;
NgR-Troy;
NME1 (NM23A);
NOX5;
NPPB;
NR0B1;
NR0B2;
NR1D1;
NR1D2;
NR1H2;
NR1H3;
NR1H4;
NRII2;
NRII3;
NR2C1;
NR2C2;
NR2E1;
NR2E3;
NR2F1;
NR2F2;
NR2F6;
NR3C1;
NR3C2;
NR4A1;
NR4A2;
NR4A3;
NR5A1;
NR5A2;
NR6A1;
NRP1;
NRP2;
NT5E;
NTN4;
ODZ1;
OPRD1;
P2RX7;
PAP;
PART1;
PATE;
PAWR;
PCA3;
PCNA;
PDGFA;
PDGFB;
PECAM1;
PF4 (CXCL4);
PGF;
PGR;
phosphacan;
PIAS2;
PIK3CG;
PLAU (uPA);
PLG;
PLXDC1;
PPBP (CXCL7);
PPID;
PR1;
PRKCQ;
PRKD1;
PRL;
PROC;
PROK2;
PSAP;
PSCA;
PTAFR;
PTEN;
PTGS2 (COX-2);
PTN;
RAC2 (p21Rac2);
RARB;
RGS1;
RGS13;
RGS3;
RNF110 (ZNF144);
ROBO2;
SI00A2;
SCGB1D2 (lipophilin B);
SCGB2A1 (mammaglobin
2);
SCGB2A2 (mammaglobin
1);
SCYE1 (endothelial Monocyte-activating cytokine);
SDF2;
SERPINA1;
SERPINA3;
SERPINB5 (maspin);
SERPINE1 (PAI-1);
SERPINF1;
SHBG;
SLA2;
SLC2A2;
SLC33A1;
SLC43A1;
SLIT2;
SPP1;
SPRR1B (Spr1);
ST6GAL1;
STAB1;
STAT6;
STEAP;
STEAP2;
TB4R2;
TBX21;
TCP10;
TDGF1;
TEK;
TGFA;
TGFB1;
TGFB111;
TGFB2;
TGFB3;
TGFBI;
TGFBR1;
TGFBR2;
TGFBR3;
TH1L;
THBS1 (thrombospondin-1);
THBS2;
THBS4;
THPO;
TIE (Tie-1);
TIMP3;
tissue factor;
TLR10;
TLR2;
TLR3;
TLR4;
TLR5;
TLR6;
TLR7;
TLR8;
TLR9;
TNF;
TNF-a;
TNFAIP2 (B94);
TNFAIP3;
TNFRSF11A;
TNFRSF1A;
TNFRSF1B;
TNFRSF21;
TNFRSF5;
TNFRSF6 (Fas);
TNFRSF7;
TNFRSF8;
TNFRSF9;
TNFSF10 (TRAIL);
TNFSF11 (TRANCE);
TNFSF12 (APO3L);
TNFSF13 (April);
TNFSF13B;
TNFSF14 (HVEM-L);
TNFSF15 (VEGI);
TNFSF18;
TNFSF4 (OX40 ligand);
TNFSF5 (CD40 ligand);
TNFSF6 (FasL);
TNFSF7 (CD27 ligand);
TNFSF8 (CD30 ligand);
TNFSF9 (4-1BB ligand);
TOLLIP;
Toll-like receptors;
TOP2A (topoisomerase Iia);
TP53;
TPM1;
TPM2;
TRADD;
TRAF1;
TRAF2;
TRAF3;
TRAF4;
TRAF5;
TRAF6;
TREM1;
TREM2;
TRPC6;
TSLP;
TWEAK;
VEGF;
VEGFB;
VEGFC;
versican;
VHL C5;
VLA-4;
XCL1 (lymphotactin);
XCL2 (SCM-1b);
XCR1 (GPR5/CCXCR1);
YY1; and
ZFPM2.
- ACVR1;
-
4. The binding protein according to claim 1, wherein said binding protein is capable of binding a two targets, wherein the two targets are selected from the group consisting of CD138 and CD20;
- CD138 and CD40;
CD20 and CD3;
CD38 &
CD138;
CD38 and CD20;
CD38 and CD40;
CD40 and CD20;
CD19 and CD20;
CD-8 and IL-6;
PDL-1 and CTLA-4;
CTLA-4 and BTNO2;
CSPGs and RGM A;
IGF1 and IGF2;
IGF1/2 and Erb2B;
IL-12 and IL-18;
IL-12 and TWEAK;
IL-13 and ADAM8;
IL-13 and CL25;
IL-13 and IL-1beta;
IL-13 and IL-25;
IL-13 and IL-4;
IL-13 and IL-5;
IL-13 and IL-9;
IL-13 and LHR agonist;
IL-13 and MDC;
IL-13 and MIF;
IL-13 and PED2;
IL-13 and SPRR2a;
IL-13 and SPRR2b;
IL-13 and TARC;
IL-13 and TGF-β
;
IL-1α and
IL-1β
;
MAG and RGM A;
NgR and RGM A;
NogoA and RGM A;
OMGp and RGM A;
RGM A and RGM B;
Te38 and TNFα
;
TNFα and
IL-12;
TNFα and
IL-12p40;
TNFα and
IL-13;
TNFα and
IL-15;
TNFα and
IL-17;
TNFα and
IL-18;
TNFα and
IL-1beta;
TNFα and
IL-23;
TNFα and
MIF;
TNFα and
PEG2;
TNFα and
PGE4;
TNFα and
VEGF; and
VEGFR and EGFR;
TNFα and
RANK ligand;
TNFα and
Blys;
TNFα and
GP130;
TNFα and
CD-22; and
TNFα and
CTLA-4.
- CD138 and CD40;
-
5. The binding protein according to claim 2, wherein the binding protein is capable of modulating a biological function of one or more targets.
-
6. The binding protein according to claim 2, wherein the binding protein is capable of neutralizing one or more targets.
-
7. The binding protein according to claim 2, wherein said one or more targets is selected from the group consisting of cytokine, chemokine, cell surface protein, enzyme and receptor.
-
8. The binding protein according to claim 7 wherein the cytokine is selected from the group consisting of lymphokines, monokines, and polypeptide hormones.
-
9. The binding protein according to claim 8, wherein said cytokines are IL-1α
- and IL-1β
.
- and IL-1β
-
10. The binding protein according to claim 9, wherein the binding protein comprises a DVD heavy chain amino acid sequence selected from the group consisting of SEQ ID NO. 33, SEQ ID NO. 37, SEQ ID NO. 41, SEQ ID NO. 45, SEQ ID NO. 47, SEQ ID NO. 51, SEQ ID NO. 53, SEQ ID NO. 55, SEQ ID NO. 57, and SEQ ID NO. 59;
- and a DVD light chain amino acid sequence selected from the group consisting of SEQ ID NO. 35, SEQ ID NO. 39, SEQ ID NO. 43, SEQ ID NO. 46, SEQ ID NO. 49, SEQ ID NO. 52, SEQ ID NO. 54, SEQ ID NO. 56, SEQ ID NO. 58, and SEQ ID NO. 60.
-
11. The binding protein according to claim 8, wherein said cytokines are TNF-α
- and IL-13.
-
12. The binding protein according to claim 8, wherein said cytokines are IL-12 and IL-18.
-
13. The binding protein according to claim 12, wherein the binding protein comprises a DVD heavy chain amino acid sequence selected from the group consisting of SEQ ID NO. 83, SEQ ID NO. 90, SEQ ID NO. 93, SEQ ID NO. 95, and SEQ ID NO. 114;
- and a DVD light chain amino acid sequence selected from the group consisting of SEQ ID NO. 86, SEQ ID NO. 91, SEQ ID NO. 94, SEQ ID NO. 46, SEQ ID NO. 96, and SEQ ID NO. 116.
-
14. The binding protein according to claim 7 wherein the chemokine is selected from the group consisting of CCR2, CCR5 and CXCL-13.
-
15. The binding protein according to claim 7 wherein the cell surface protein is an integrin.
-
16. The binding protein according to claim 7 wherein the cell surface proteins are CD-20 and CD3.
-
17. The binding protein according to claim 16, wherein the binding protein comprises a DVD heavy chain amino acid sequence is SEQ ID NO. 97, and a DVD light chain SEQ ID NO. 101.
-
18. The binding protein according to claim 7 wherein the enzyme is selected from the group consisting of kinases and proteases.
-
19. The binding protein according to claim 7 wherein the receptor is selected from the group consisting of lymphokine receptor, monokine receptor, and polypeptide hormone receptor.
-
20. The binding protein according to claim 7, wherein said binding protein has an on rate constant(Kon) to said one or more targets selected from the group consisting of:
- at least about 102M−
1s−
1;
at least about 103M−
1s−
1, at least about 104M−
1s−
1;
at least about 105M−
1s−
1; and
at least about 106M−
1s−
1, as measured by surface plasmon resonance.
- at least about 102M−
-
21. The binding protein according to claim 7, wherein said binding protein has an off rate constant(Koff) to said one or more targets selected from the group consisting of:
- at most about 10−
3s−
1;
at most about 10−
4s−
1;
at most about 10−
5s−
1; and
at most about 10−
6s−
1, as measured by surface plasmon resonance.
- at most about 10−
-
22. The binding protein according to claim 7, wherein said binding protein has a dissociation constant (KD) to said one or more targets selected from the group consisting of:
- at most about 10−
7 M;
at most about 10−
8 M;
at most about 10−
9 M;
at most about 10−
10 M;
at most about 10−
11 M;
at most about 10−
12 M; and
at most 10−
13 M.
- at most about 10−
-
23. A binding protein conjugate comprising a binding protein described in any one of claims 1-8, 12, and 13, said binding protein conjugate further comprising an agent selected from the group consisting of;
- an immunoadhension molecule, an imaging agent, a therapeutic agent, and a cytotoxic agent.
-
24. The binding protein conjugate according to claim 23, wherein said agent is an imaging agent selected from the group consisting of a radiolabel, an enzyme, a fluorescent label, a luminescent label, a bioluminescent label, a magnetic label, and biotin.
-
25. The binding protein conjugate according to claim 24, wherein said imaging agent is a radiolabel selected from the group consisting of:
- 3H, 14C, 35S, 90Y, 99Tc, 111In, 125I, 131I, 177Lu, 166Ho, and 153Sm.
-
26. The binding protein conjugate according to claim 23, wherein said agent is a therapeutic or cytotoxic agent selected from the group consisting of;
- an anti-metabolite, an alkylating agent, an antibiotic, a growth factor, a cytokine, an anti-angiogenic agent, an anti-mitotic agent, an anthracycline, toxin, and an apoptotic agent.
-
27. The binding protein according to claim 1, wherein said binding protein is a crystallized binding protein.
-
28. The crystallized binding protein according to claim 27, wherein said crystal is a carrier-free pharmaceutical controlled release crystal.
-
29. The crystallized binding protein according to claim 27, wherein said binding protein has a greater half life in vivo than the soluble counterpart of said binding protein.
-
30. The crystallized binding protein according to claim 27, wherein said binding protein retains biological activity.
-
31. A binding protein described in claim 1 produced according to a method comprising culturing a host cell in culture medium under conditions sufficient to produce said binding protein, wherein said host cell comprises a vector, said vector comprising a nucleic acid encoding said binding protein.
-
32. A pharmaceutical composition comprising a binding protein of any one of claims 1-8, 12, 13, 27-30, and 31, and a pharmaceutically acceptable carrier.
-
33. The pharmaceutical composition of claim 32 further comprising at least one additional therapeutic agent.
-
34. The binding protein according to any one of claims 1-6, wherein the linker XI is selected from the group consisting of AKTTPKLEEGEFSEAR (SEQ ID NO:
- 118);
AKTTPKLEEGEFSEARV (SEQ ID NO;
119);
AKTTPKLGG (SEQ ID NO;
120);
SAKTTPKLGG (SEQ ID NO;
121);
SAKTTP (SEQ ID NO;
122);
RADAAP (SEQ ID NO;
123);
RADAAPTVS (SEQ ID NO;
124);
RADAAAAGGPGS (SEQ ID NO;
125);
RADAAAA(G4S)4 (SEQ ID NO;
126);
SAKTTPKLEEGEFSEARV (SEQ ID NO;
127);
ADAAP (SEQ ID NO;
40);
ADAAPTVSIFPP (SEQ ID NO;
103);
TVAAP (SEQ ID NO;
44);
TVAAPSVFIFPP (SEQ ID NO;
50);
QPKAAP (SEQ ID NO;
88);
QPKAAPSVTLFPP (SEQ ID NO;
92);
AKTTPP (SEQ ID NO;
38);
AKTTPPSVTPLAP (SEQ ID NO;
128);
AKTTAP (SEQ ID NO;
129);
AKTTAPSVYPLAP (SEQ ID NO;
99);
ASTKGP (SEQ ID NO;
42);
ASTKGPSVFPLAP (SEQ ID NO;
48);
GGGGSGGGGSGGGGS (SEQ ID NO;
130);
GENKVEYAPALMALS (SEQ ID NO;
131);
GPAKELTPLKEAKVS (SEQ ID NO;
132); and
GHEAAAVMQVQYPAS (SEQ ID NO;
133).
- 118);
-
35. The pharmaceutical composition according to claim 33, wherein said additional agent is a therapeutic or imaging agent.
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36. The pharmaceutical composition of claim 35, wherein said additional agent is selected from the group consisting of:
- Therapeutic agent, imaging agent, cytotoxic agent, angiogenesis inhibitors;
kinase inhibitors;
co-stimulation molecule blockers;
adhesion molecule blockers;
anti-cytokine antibody or functional fragment thereof;
methotrexate;
cyclosporin;
rapamycin;
FK506;
detectable label or reporter;
a TNF antagonist;
an antirheumatic;
a muscle relaxant, a narcotic, a non-steroid anti-inflammatory drug (NSAID), an analgesic, an anesthetic, a sedative, a local anesthetic, a neuromuscular blocker, an antimicrobial, an antipsoriatic, a corticosteriod, an anabolic steroid, an erythropoietin, an immunization, an immunoglobulin, an immunosuppressive, a growth hormone, a hormone replacement drug, a radiopharmaceutical, an antidepressant, an antipsychotic, a stimulant, an asthma medication, a beta agonist, an inhaled steroid, an epinephrine or analog, a cytokine, and a cytokine antagonist.
- Therapeutic agent, imaging agent, cytotoxic agent, angiogenesis inhibitors;
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37. A pharmaceutical composition comprising a binding protein conjugate according to claim 23 and a pharmaceutically acceptable carrier.
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38. The pharmaceutical composition according to claim 37, wherein said binding protein congjugate comprises an imaging agent selected from the group consisting of a radiolabel, an enxyme, a fluorescent labe, a luminescent label, a bioluminescent label, a magnetic label, and biotin.
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39. The pharmaceutical composition according to claim 38, wherein said imaging agent is a radiolabel selected from the group consisting of:
- 3H, 14C, 35S, 90Y, 99Tc, 11In, 125I, 131I, 177Lu, 166Ho, and 153Sm.
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40. The pharamaceutical composition according to claim 37, wherein said binding protein conjugate comprises a therapeutic or cytotoxic agent selected from the group consisting of an anti-metabolite, an alkylating agent, an antibiotic, a growth factor, a cytokine, an anti-angiogenic agent, an anti-mitotic agent, an anthracycline, a toxin, and an apoptotic agent.
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41. The pharmaceutical composition of claim 37 further comprising a second agent.
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42. The pharmaceutical composition of claim 41, wherein said second agent is a therapeutic or imaging agent.
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43. The pharmaceutical composition of claim 42, wherein said therapeutic or imaging agent is selected from the group:
- cytotoxic agent, angiogenesis inhibitors, kinase inhibitors;
co-stimulation molecule blockers;
adhesion molecule blockers;
anti-cytokine antibody or functional fragment thereof;
methotrexate;
cyclosporin;
rapamycin;
FK506;
detectable label or reportor;
a TNF antagonist;
an antiheumatic;
a muscle relaxant, a narcotic, anon-steroid anti-inflammatory dug (NSAID), an analgesic, an anesthetic, a sedative, a local anesthetic, a neuromuscular blocker, an antimicrobial, an antipsoriatic, a corticosteriod, an anabolic steroid, an erythropoietin, an immunization, an immunoglobulin, an immunosuppresive, a growth hormone, a hormone replacement drug, a radiopharmaceutical, 3H, 14C, 35S, 90Y, 99Tc, 111In, 125I, 131I, 177Lu, 166Ho, 153Sm, a fluorescent label, a luminescent label, a bioluminescent label, a magnetic label, biotin, an antidepressant, an antipsychotic, a stimulant, an asthma medication, a beta agonist, an inhaled steroid, an epinephrine or analog, a cytokine, and a cytokine antagonist.
- cytotoxic agent, angiogenesis inhibitors, kinase inhibitors;
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2. The binding protein according to claim 1, wherein said binding protein is capable of binding one or more targets.
- and two polypeptide chains comprise VD1-(X1)n-VD2-C-(X2)n, wherein VD1 is a first light chain variable domain, VD2 is a second light chain variable domain, C is a light chain constant domain, X1 is a linker with the proviso that it is not CH1, and X2 does not comprise an Fc region; and
Specification
- Resources
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Current AssigneeAbbvie Incorporated
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Original AssigneeAbbott Laboratories
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InventorsDixon, Richard W., Wu, Chengbin, Salfeld, Jochen G., Ghayur, Tariq
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Primary Examiner(s)Blanchard; David J.
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Assistant Examiner(s)GUSSOW, ANNE
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Application NumberUS11/507,050Publication NumberTime in Patent Office1,173 DaysField of SearchNoneUS Class Current530/387.3CPC Class CodesA61K 2039/505 comprising antibodiesA61K 39/3955 against proteinaceous mater...A61K 45/06 Mixtures of active ingredie...A61K 47/42 Proteins; Polypeptides; Deg...A61K 47/6803 Drugs conjugated to an anti...A61K 51/1093 conjugates with carriers be...A61P 1/00 Drugs for disorders of the ...A61P 1/16 for liver or gallbladder di...A61P 11/00 Drugs for disorders of the ...A61P 11/06 AntiasthmaticsA61P 13/12 of the kidneysA61P 15/00 Drugs for genital or sexual...A61P 17/00 Drugs for dermatological di...A61P 17/06 AntipsoriaticsA61P 19/02 for joint disorders, e.g. a...A61P 19/04 for non-specific disorders ...A61P 19/10 for osteoporosisA61P 21/00 Drugs for disorders of the ...A61P 21/02 Muscle relaxants, e.g. for ...A61P 23/00 AnaestheticsA61P 25/00 : Drugs for disorders of the ...A61P 25/06 : Antimigraine agentsA61P 25/16 : Anti-Parkinson drugsA61P 25/18 : Antipsychotics, i.e. neurol...A61P 25/24 : AntidepressantsA61P 25/28 : for treating neurodegenerat...A61P 25/32 : Alcohol-abuseA61P 29/00 : Non-central analgesic, anti...A61P 3/10 : for hyperglycaemia, e.g. an...A61P 31/00 : Antiinfectives, i.e. antibi...A61P 31/04 : Antibacterial agentsA61P 31/12 : AntiviralsA61P 31/18 : for HIVA61P 35/00 : Antineoplastic agentsA61P 35/02 : specific for leukemiaA61P 37/06 : Immunosuppressants, e.g. dr...A61P 37/08 : Antiallergic agents antiast...A61P 41/00 : Drugs used in surgical meth...A61P 7/06 : AntianaemicsA61P 9/00 : Drugs for disorders of the ...A61P 9/10 : for treating ischaemic or a...C07K 16/22 : against growth factors ; ag...C07K 16/24 : against cytokines, lymphoki...C07K 16/241 : Tumor Necrosis FactorsC07K 16/244 : Interleukins [IL]C07K 16/245 : IL-1C07K 16/2809 : against the T-cell receptor...C07K 16/2887 : against CD20C07K 16/2896 : against molecules with a "C...C07K 16/40 : against enzymesC07K 16/46 : Hybrid immunoglobulins hybr...C07K 16/467 : Igs with modifications in t...C07K 16/468 : Immunoglobulins having two ...C07K 2317/24 : containing regions, domains...C07K 2317/31 : multispecificC07K 2317/51 : Complete heavy chain or Fd ...C07K 2317/522 : CH1 domainC07K 2317/56 : variable (Fv) region, i.e. ...C07K 2317/64 : comprising a combination of...C07K 2317/76 : Antagonist effect on antige...Y02A 50/30 : Against vector-borne diseas...