CA2487060A1 - Humanized immunomodulatory monoclonal antibodies for the treatment of neoplastic disease or immunodeficiency - Google Patents
Humanized immunomodulatory monoclonal antibodies for the treatment of neoplastic disease or immunodeficiency Download PDFInfo
- Publication number
- CA2487060A1 CA2487060A1 CA002487060A CA2487060A CA2487060A1 CA 2487060 A1 CA2487060 A1 CA 2487060A1 CA 002487060 A CA002487060 A CA 002487060A CA 2487060 A CA2487060 A CA 2487060A CA 2487060 A1 CA2487060 A1 CA 2487060A1
- Authority
- CA
- Canada
- Prior art keywords
- seq
- antibody
- cdr
- humanized
- kappa
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/42—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Veterinary Medicine (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Virology (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The present invention provides to a humanized monoclonal antibody having immunostimulatory effects. This antibody binds specifically to B lymphoblastoid cells, induces proliferation and activation of peripheral blo od lymphocytes, and is capable of eliciting an anti-tumor effect upon administration to subjects suffering from cancer.
Claims (51)
1. An humanized monoclonal antibody having at least one complementarity determining region (CDR) of murine monoclonal antibody BAT-1 (mBAT-1) and a framework region (FR) derived from an acceptor human immunoglobulin wherein the humanized antibody retains the anti-tumor activity of mBAT-1 monoclonal antibody and is less immunogenic in a human subject than said marine antibody.
2. The humanized monoclonal antibody of claim 1 wherein the humanized antibody induces a greater anti-tumor effect than that induced by the parent marine BAT-1 antibody.
3. The humanized antibody of claim 1 comprising the complementarity-determining regions (CDRs) of murine monoclonal antibody BAT-1 (mBAT-1), wherein said humanized antibody comprises:
a. light chain variable regions of the formula:
wherein each FR is independently a framework region of a human antibody, and each CDR is a complementarity determining region, derived from mBAT-1;
b. the heavy chain variable regions of the formula:
wherein each FR is separately a framework region of a human antibody, and each CDR is a complementarity determining region, form mBAT-1.
a. light chain variable regions of the formula:
wherein each FR is independently a framework region of a human antibody, and each CDR is a complementarity determining region, derived from mBAT-1;
b. the heavy chain variable regions of the formula:
wherein each FR is separately a framework region of a human antibody, and each CDR is a complementarity determining region, form mBAT-1.
4. A monoclonal antibody having a genetically modified Fab region comprising the complementarity-determining regions (CDRs) of marine monoclonal antibody BAT-1 (mBAT-1), wherein the genetically modified antibody retains the biological activity of said mBAT-1 and wherein said genetically modified monoclonal antibody comprises an amino acid sequence selected from:
(i) a heavy chain variable region comprising the amino acid sequences of: CDR
H1 (SEQ
ID NO:12); CDR H2 (SEQ ID NO:13); CDR H3 (SEQ ID NO:14); and a light chain variable region comprising the amino acid sequences of: CDR L1 (SEQ ID NO:9);
CDR L2 (SEQ ID NO:10); CDR L3 (SEQ ID NO:11);
(ii) heavy chain and light chain variable regions comprising the amino acid sequences having greater than about 80 percent similarity to all or part of the sequences of:
CDR H1 (SEQ ID NO:12); CDR H2 (SEQ ID NO:13); CDR H3 (SEQ ID NO:14); CDR L1 (SEQ ID NO:9); CDR (SEQ ID NO:10); CDR L3 (SEQ ID NO:11);
(iii) an antibody of (i) or (ii) in which one or more amino acid residues have been added, deleted, replaced or chemically modified without substantially affecting the biological activity or binding specificity of the antibody.
(i) a heavy chain variable region comprising the amino acid sequences of: CDR
H1 (SEQ
ID NO:12); CDR H2 (SEQ ID NO:13); CDR H3 (SEQ ID NO:14); and a light chain variable region comprising the amino acid sequences of: CDR L1 (SEQ ID NO:9);
CDR L2 (SEQ ID NO:10); CDR L3 (SEQ ID NO:11);
(ii) heavy chain and light chain variable regions comprising the amino acid sequences having greater than about 80 percent similarity to all or part of the sequences of:
CDR H1 (SEQ ID NO:12); CDR H2 (SEQ ID NO:13); CDR H3 (SEQ ID NO:14); CDR L1 (SEQ ID NO:9); CDR (SEQ ID NO:10); CDR L3 (SEQ ID NO:11);
(iii) an antibody of (i) or (ii) in which one or more amino acid residues have been added, deleted, replaced or chemically modified without substantially affecting the biological activity or binding specificity of the antibody.
5. The monoclonal antibody of Claim 4, wherein the framework regions (FRs) are derived from a human antibody.
6. The humanized monoclonal antibody of claim 3 comprising complementarity-determining regions (CDRs) of murine monoclonal antibody BAT-1 (mBAT-1), wherein said humanized antibody comprises:
a. light chain variable regions of the formula:
wherein each FR is independently a framework region of a human antibody, and each CDR is a complementarity determining region, wherein the amino acid sequence of DR L1 is SARSSVSYMH (SEQ. ID NO. 9); CDR L2 is RTSNLAS (SEQ. ID NO. 10);
CDRL3 is QQRSSFPLT (SEQ. ID NO. 11);
b. the heavy chain variable regions of the formula:
FR H1-CDR H1- FR H2-CDR H2- FR H3-CDR H3- FR H4.
wherein each FR is separately a framework region of a human antibody, and each CDR is a complementarity determining region, wherein the amino acid sequence of CDR H1 is NYGMN (SEQ. ID NO. 12); CDR H2 is WINTDSGESTYAEEFKG (SEQ.
ID NO. 13); CDR H3 is VGYDALDY (SEQ. ID NO. 14).
a. light chain variable regions of the formula:
wherein each FR is independently a framework region of a human antibody, and each CDR is a complementarity determining region, wherein the amino acid sequence of DR L1 is SARSSVSYMH (SEQ. ID NO. 9); CDR L2 is RTSNLAS (SEQ. ID NO. 10);
CDRL3 is QQRSSFPLT (SEQ. ID NO. 11);
b. the heavy chain variable regions of the formula:
FR H1-CDR H1- FR H2-CDR H2- FR H3-CDR H3- FR H4.
wherein each FR is separately a framework region of a human antibody, and each CDR is a complementarity determining region, wherein the amino acid sequence of CDR H1 is NYGMN (SEQ. ID NO. 12); CDR H2 is WINTDSGESTYAEEFKG (SEQ.
ID NO. 13); CDR H3 is VGYDALDY (SEQ. ID NO. 14).
7. The humanized antibody of Claim 6, wherein said humanized antibody induces a greater antitumor effect than murine BAT-1 monoclonal antibody.
8. The humanized antibody of Claim 6, wherein said humanized antibody induces a greater anti-metastatic effect than murine BAT-1 monoclonal antibody.
9. The humanized antibody of claim 6, wherein the antibody is a full length antibody.
10. The humanized antibody of Claim 9, wherein the antibody is of isotype IgG.
11. The humanized antibody of Claim 10, wherein said isotype subclass is selected from IgG1 or IgG4.
12. The humanized antibody of Claim 6, wherein the FR of the heavy chain variable region are derived from the FRs of the heavy chain variable region of the human hsighv1295 antibody.
13. The humanized antibody of Claim 6, wherein the FRs of the kappa light chain variable region are based on the FRs of the kappa light chain variable region of the human TEL9 antibody.
14. The humanized antibody of claim 6, having a human kappa constant region.
15. An antibody fragment derived from humanized antibody of claim 6, wherein the antibody fragment is selected from the group consisting of Fv, F(ab'), F(ab')a, a single chain antibody.
16. The humanized antibody of claim 6, wherein the antibody is further labeled with a detectable label, immobilized on a solid phase, or conjugated to a heterologous compound.
17. The humanized antibody of claim 6, wherein said humanized monoclonal antibody light chain variable regions are selected from the group consisting of: BATR.kappa.A
(SEQ ID NO.
15), BATR.kappa.B (SEQ. ID NO. 16), BATR.kappa.C (SEQ. ID NO. 17), BATR.kappa.D (SEQ. ID NO.
(SEQ ID NO.
15), BATR.kappa.B (SEQ. ID NO. 16), BATR.kappa.C (SEQ. ID NO. 17), BATR.kappa.D (SEQ. ID NO.
18), and the heavy chain variable regions are selected from the group consisting of BATRH A (SEQ. ID NO. 20), BATRH B (SEQ. ID NO. 21), BATRH C (SEQ. ID NO. 22), BATRH D (SEQ. ID NO. 23) or BATRH E (SEQ. ID NO. 24).
18. The humanized antibody of claim 6, wherein said humanized monoclonal antibody variable regions are selected from the group consisting of BATRH
A/BATR.kappa.A (SEQ. ID
NO. 20/SEQ. ID NO. 15), BATRH B/BATR.kappa.A (SEQ. ID NO. 21/SEQ. ID NO. 15), BATRH B/BATR.kappa.B (SEQ. ID NO. 21/SEQ. ID NO. 16), BATRH C/BATR.kappa.B
(SEQ. ID NO.
22/SEQ. ID NO. 16), BATRH B/BATR.kappa.D (SEQ. ID NO. 21/SEQ. ID NO. 18), or BATRH C/BATR.kappa.D (SEQ. ID NO. 22/SEQ. ID NO. 18).
18. The humanized antibody of claim 6, wherein said humanized monoclonal antibody variable regions are selected from the group consisting of BATRH
A/BATR.kappa.A (SEQ. ID
NO. 20/SEQ. ID NO. 15), BATRH B/BATR.kappa.A (SEQ. ID NO. 21/SEQ. ID NO. 15), BATRH B/BATR.kappa.B (SEQ. ID NO. 21/SEQ. ID NO. 16), BATRH C/BATR.kappa.B
(SEQ. ID NO.
22/SEQ. ID NO. 16), BATRH B/BATR.kappa.D (SEQ. ID NO. 21/SEQ. ID NO. 18), or BATRH C/BATR.kappa.D (SEQ. ID NO. 22/SEQ. ID NO. 18).
19. The antibody of Claim 6 generated by recombinant DNA technology, utilizing CDR
grafting.
grafting.
20. An isolated polynucleotide construct encoding any of the monoclonal antibodies of Claims 1-19 or fragments thereof.
21. The isolated polynucleotide construct according to Claim 20 encoding a kappa light chain variable region selected from the group consisting of SEQ ID NO. 15, SEQ ID
NO. 16, SEQ ID NO. 17, SEQ ID NO. 18.
NO. 16, SEQ ID NO. 17, SEQ ID NO. 18.
22. The isolated polynucleotide construct according to Claim 21 selected from the group consisting of: SEQ ID NO. 87, SEQ ID NO. 88, SEQ ID NO. 89.
23. The isolated polynucleotide construct according to Claim 20 encoding a heavy chain variable region selected from the group consisting of SEQ ID NO. 20, SEQ ID
NO. 21, SEQ ID NO. 22, SEQ ID NO. 23, SEQ ID NO. 24.
NO. 21, SEQ ID NO. 22, SEQ ID NO. 23, SEQ ID NO. 24.
24. The isolated polynucleotide construct according to Claim 23 selected from the group consisting of SEQ ID NO. 90, SEQ ID NO. 91, SEQ ID NO: 92.
25. A vector comprising any of the polynucleotides of Claim 20 to 24.
26. The vector of Claim 25, further comprising at least one polynucleotide sequence encoding a component selected from the group consisting of a promoter operatively linked to the polynucleotide encoding the antibody, one or more resistance gene, a Kozak sequence, an origin of replication, one or more selection marker genes, an enhancer element, transcription terminator, a signal peptide, genomic human kappa constant region, genomic human IgG constant region.
27. The vector of Claim 26, wherein the vector is a plasmid or a virus.
28. The vector of Claim 27, selected from the group comprising: pKN110, pG1D200, pG1KD210, pUC or pBR322.
29. The vector of Claim 25, comprising the polynucleotide sequence of SEQ ID
NO. 93.
NO. 93.
30. A host cell comprising the vector of any of Claims 23-27.
31. The host cell of Claim 30, capable of expressing an antibody or fragments thereof.
32. The host cell Claim 30, wherein the cell is selected from eukaryotic and prokaryotic.
33. The host cell of Claim 30, selected from the group consisting of: CHO, CHOdhfr, NSO, COS or COS7 cells.
34. A pharmaceutical composition comprising as an active ingredient the antibody or antibody fragments of any of Claims 1-19.
35. The pharmaceutical composition of Claim 34, further comprising a physiologically acceptable carrier, diluent, or stabilizer.
36. A method for treating a subject in need thereof, comprising the step of treating said subject with a therapeutically effective amount of a pharmaceutical composition containing as an active ingredient the antibody or antibody fragments of any of Claims 1-19.
37. The method for treating a subject of Claim 36 further comprising treatment in conjunction with additional therapeutic agents selected from, cytokines, IL-1 (interleuken-1), IL-2, IL-6, IFN-.alpha. (interferon-.alpha.), cell vaccines, antibodies, T-cell stimulatory antibody, and anti-tumor therapeutic antibody.
38. The method for treating a subject of Claim 37 wherein the treatments are administered substantially at the same time.
39. The method of Claim 37 wherein the treatments are co-administered in a single composition.
40. The method of Claim 37 wherein the treatments are administered in separate compositions.
41. The method for treating a subject of Claim 37 wherein the treatments are administered sequentially.
42. The method of any of Claim 36, further comprising cell therapy.
43. The method for treating a subject of Claim 42 wherein the treatments are administered substantially at the same time.
44. The method of Claim 42 wherein the treatments are co-administered in a single composition.
45. The method of Claim 42 wherein the treatments are administered in separate compositions.
46. The method for treating a subject of Claim 47 wherein the treatments are administered sequentially.
47. The method of any one of Claims 42 through 46 wherein the cells are selected from autologous and allogeneic cells.
48. The method of any of Claim 36 through 47, wherein the treatments are independently selected from ex vivo and in vivo.
49. The method of any of Claim 36 through 47, for treating cancer.
50. The method of Claim 49, wherein the cancer is selected from melanoma, lung tumors, colorectal cancer or hepatic metastasis.
51. A method for producing the antibody of any of Claims 1-19, comprising:
(i) transfecting a host cell with a vector comprising a polynucleotide sequence encoding said antibody, or co-transfecting the host cell with 2 vectors each comprising a polynucleotide sequence encoding the heavy or light chain regions of said antibody;
(ii) culturing the host cell of (i) so that said antibody is expressed; and (iii) recovering the antibody from the host cells culture of (ii).
(i) transfecting a host cell with a vector comprising a polynucleotide sequence encoding said antibody, or co-transfecting the host cell with 2 vectors each comprising a polynucleotide sequence encoding the heavy or light chain regions of said antibody;
(ii) culturing the host cell of (i) so that said antibody is expressed; and (iii) recovering the antibody from the host cells culture of (ii).
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IL149820 | 2002-05-23 | ||
IL14982002A IL149820A0 (en) | 2002-05-23 | 2002-05-23 | Humanized immunomodulatory monoclonal antibodies for the treatment of neoplastic disease or immunodeficiency |
PCT/IL2003/000425 WO2003099196A2 (en) | 2002-05-23 | 2003-05-22 | Humanized immunomodulatory monoclonal antibodies for the treatment of neoplastic disease or immunodeficiency |
Publications (2)
Publication Number | Publication Date |
---|---|
CA2487060A1 true CA2487060A1 (en) | 2003-12-04 |
CA2487060C CA2487060C (en) | 2011-01-04 |
Family
ID=28460428
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA2487060A Expired - Fee Related CA2487060C (en) | 2002-05-23 | 2003-05-22 | Humanized immunomodulatory monoclonal antibodies for the treatment of neoplastic disease or immunodeficiency |
Country Status (14)
Country | Link |
---|---|
US (3) | US7332582B2 (en) |
EP (1) | EP1575484B1 (en) |
JP (2) | JP4764627B2 (en) |
KR (1) | KR101169254B1 (en) |
AU (1) | AU2003230183B2 (en) |
CA (1) | CA2487060C (en) |
CY (1) | CY1117114T1 (en) |
DK (1) | DK1575484T3 (en) |
ES (1) | ES2549303T3 (en) |
HU (1) | HUE025710T2 (en) |
IL (3) | IL149820A0 (en) |
PT (1) | PT1575484E (en) |
SI (1) | SI1575484T1 (en) |
WO (1) | WO2003099196A2 (en) |
Families Citing this family (240)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL129299A0 (en) | 1999-03-31 | 2000-02-17 | Mor Research Applic Ltd | Monoclonal antibodies antigens and diagnosis of malignant diseases |
ES2390425T3 (en) | 2000-12-22 | 2012-11-12 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Use of repulsive targeting molecules (RGM) and their modulators |
FI2206517T3 (en) | 2002-07-03 | 2023-10-19 | Ono Pharmaceutical Co | Immunopotentiating compositions comprising anti-PD-L1 antibodies |
JP4511943B2 (en) * | 2002-12-23 | 2010-07-28 | ワイス エルエルシー | Antibody against PD-1 and use thereof |
WO2006021955A2 (en) * | 2004-08-23 | 2006-03-02 | Mor Research Applications Ltd. | Use of bat monoclonal antibody for immunotherapy |
LT2439273T (en) | 2005-05-09 | 2019-05-10 | Ono Pharmaceutical Co., Ltd. | Human monoclonal antibodies to programmed death 1(PD-1) and methods for treating cancer using anti-PD-1 antibodies alone or in combination with other immunotherapeutics |
CN105330741B (en) | 2005-07-01 | 2023-01-31 | E.R.施贵宝&圣斯有限责任公司 | Human monoclonal antibodies to programmed death ligand 1 (PD-L1) |
US8906864B2 (en) | 2005-09-30 | 2014-12-09 | AbbVie Deutschland GmbH & Co. KG | Binding domains of proteins of the repulsive guidance molecule (RGM) protein family and functional fragments thereof, and their use |
DK2170959T3 (en) | 2007-06-18 | 2014-01-13 | Merck Sharp & Dohme | ANTIBODIES AGAINST HUMAN PROGRAMMED DEATH RECEPTOR PD-1 |
AU2008346734A1 (en) * | 2008-01-03 | 2009-07-16 | The Scripps Research Institute | Antibody targeting through a modular recognition domain |
BRPI0907718A2 (en) * | 2008-02-11 | 2017-06-13 | Curetech Ltd | method for treating a tumor, method for improving tolerability to at least one chemotherapeutic agent, method for increasing survival of an individual having a tumor, method for reducing or preventing tumor recurrence, use of a humanized monoclonal antibody or fragment and antibody thereof humanized monoclonal or fragment thereof |
US8962803B2 (en) | 2008-02-29 | 2015-02-24 | AbbVie Deutschland GmbH & Co. KG | Antibodies against the RGM A protein and uses thereof |
UA112050C2 (en) * | 2008-08-04 | 2016-07-25 | БАЄР ХЕЛСКЕР ЛЛСі | THERAPEUTIC COMPOSITION CONTAINING MONOCLONAL ANTIBODY AGAINST TISSUE FACTOR INHIBITOR (TFPI) |
NZ591130A (en) | 2008-08-25 | 2012-09-28 | Amplimmune Inc | Compositions comprising a PD-1 antagonists and cyclophosphamide and methods of use thereof |
SG10201401604VA (en) | 2009-04-20 | 2014-08-28 | Oxford Biotherapeutics Ltd | Antibodies Specific To Cadherin-17 |
SG181563A1 (en) | 2009-12-08 | 2012-07-30 | Abbott Gmbh & Co Kg | Monoclonal antibodies against the rgm a protein for use in the treatment of retinal nerve fiber layer degeneration |
SG10201502587SA (en) | 2010-03-01 | 2015-06-29 | Bayer Healthcare Llc | Optimized monoclonal antibodies against tissue factor pathway inhibitor (tfpi) |
MX2012013068A (en) * | 2010-05-11 | 2013-03-05 | Aveo Pharmaceuticals Inc | Anti-fgfr2 antibodies. |
SG189835A1 (en) * | 2010-10-20 | 2013-06-28 | Oxford Biotherapeutics Ltd | Antibodies |
ES2671748T3 (en) | 2011-07-21 | 2018-06-08 | Tolero Pharmaceuticals, Inc. | Heterocyclic protein kinase inhibitors |
US8686119B2 (en) * | 2011-07-24 | 2014-04-01 | Curetech Ltd. | Variants of humanized immunomodulatory monoclonal antibodies |
MY176695A (en) | 2012-01-27 | 2020-08-19 | Abbvie Inc | Composition and method for the diagnosis and treatment of diseases associated with neurite degeneration |
JP6378170B2 (en) | 2012-04-12 | 2018-08-22 | イェール ユニバーシティーYale University | Vehicle for controlled delivery of different pharmaceuticals |
JP6279466B2 (en) * | 2012-04-27 | 2018-02-14 | Jcrファーマ株式会社 | New expression vector |
CN104603151A (en) * | 2012-05-31 | 2015-05-06 | 索伦托治疗有限公司 | Antigen binding proteins that bind dll-4 |
CN112587658A (en) | 2012-07-18 | 2021-04-02 | 博笛生物科技有限公司 | Targeted immunotherapy for cancer |
CN104662044B (en) | 2012-08-24 | 2018-10-30 | 加利福尼亚大学董事会 | For treating ROR1 cancers and inhibiting the antibody and vaccine that shift |
WO2014122271A1 (en) | 2013-02-07 | 2014-08-14 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for predicting the survival time of patients suffering from diffuse large b-cell lymphomas |
EP3178849B1 (en) | 2013-09-20 | 2019-03-20 | Bristol-Myers Squibb Company | Combination of anti-lag-3 antibodies and anti-pd-1 antibodies to treat tumors |
EP3049442A4 (en) | 2013-09-26 | 2017-06-28 | Costim Pharmaceuticals Inc. | Methods for treating hematologic cancers |
CA2987519A1 (en) | 2013-11-01 | 2015-05-07 | Yale University | Delivery vehicles |
US9580504B1 (en) | 2013-11-07 | 2017-02-28 | Curetech Ltd. | Pidilizumab monoclonal antibody therapy following stem cell transplantation |
DE202014010499U1 (en) | 2013-12-17 | 2015-10-20 | Kymab Limited | Targeting of human PCSK9 for cholesterol treatment |
US10548985B2 (en) | 2014-01-10 | 2020-02-04 | Birdie Biopharmaceuticals, Inc. | Compounds and compositions for treating EGFR expressing tumors |
JOP20200094A1 (en) | 2014-01-24 | 2017-06-16 | Dana Farber Cancer Inst Inc | Antibody molecules to pd-1 and uses thereof |
JOP20200096A1 (en) | 2014-01-31 | 2017-06-16 | Children’S Medical Center Corp | Antibody molecules to tim-3 and uses thereof |
JP6903432B2 (en) | 2014-03-12 | 2021-07-14 | イエダ リサーチ アンド ディベロップメント カンパニー リミテッド | Decreasing the level or activity of systemic regulatory T cells to treat CNS diseases and injuries |
US10618963B2 (en) | 2014-03-12 | 2020-04-14 | Yeda Research And Development Co. Ltd | Reducing systemic regulatory T cell levels or activity for treatment of disease and injury of the CNS |
US10519237B2 (en) | 2014-03-12 | 2019-12-31 | Yeda Research And Development Co. Ltd | Reducing systemic regulatory T cell levels or activity for treatment of disease and injury of the CNS |
US9394365B1 (en) | 2014-03-12 | 2016-07-19 | Yeda Research And Development Co., Ltd | Reducing systemic regulatory T cell levels or activity for treatment of alzheimer's disease |
EA037006B1 (en) | 2014-06-06 | 2021-01-26 | Бристол-Майерс Сквибб Компани | Antibodies against glucocorticoid-induced tumor necrosis factor receptor (gitr) and uses thereof |
TWI693232B (en) | 2014-06-26 | 2020-05-11 | 美商宏觀基因股份有限公司 | Covalently bonded diabodies having immunoreactivity with pd-1 and lag-3, and methods of use thereof |
DK3166976T3 (en) | 2014-07-09 | 2022-04-11 | Birdie Biopharmaceuticals Inc | ANTI-PD-L1 COMBINATIONS FOR TREATMENT OF TUMORS |
EP3186281B1 (en) | 2014-08-28 | 2019-04-10 | Halozyme, Inc. | Combination therapy with a hyaluronan-degrading enzyme and an immune checkpoint inhibitor |
CN112587672A (en) | 2014-09-01 | 2021-04-02 | 博笛生物科技有限公司 | anti-PD-L1 conjugates for the treatment of tumors |
US9993551B2 (en) | 2014-09-13 | 2018-06-12 | Novartis Ag | Combination therapies of EGFR inhibitors |
NZ730563A (en) | 2014-10-14 | 2019-05-31 | Halozyme Inc | Compositions of adenosine deaminase-2 (ada2), variants thereof and methods of using same |
RS60631B1 (en) | 2014-11-21 | 2020-09-30 | Bristol Myers Squibb Co | Antibodies against cd73 and uses thereof |
EP3221346B1 (en) | 2014-11-21 | 2020-09-02 | Bristol-Myers Squibb Company | Antibodies comprising modified heavy constant regions |
TWI708786B (en) | 2014-12-23 | 2020-11-01 | 美商必治妥美雅史谷比公司 | Antibodies to tigit |
WO2016127052A1 (en) | 2015-02-05 | 2016-08-11 | Bristol-Myers Squibb Company | Cxcl11 and smica as predictive biomarkers for efficacy of anti-ctla4 immunotherapy |
SG10201913500TA (en) | 2015-05-29 | 2020-03-30 | Agenus Inc | Anti-ctla-4 antibodies and methods of use thereof |
CA2987410A1 (en) | 2015-05-29 | 2016-12-08 | Bristol-Myers Squibb Company | Antibodies against ox40 and uses thereof |
CN107613980A (en) | 2015-05-31 | 2018-01-19 | 源生公司 | combination composition for immunotherapy |
TWI773646B (en) | 2015-06-08 | 2022-08-11 | 美商宏觀基因股份有限公司 | Lag-3-binding molecules and methods of use thereof |
TW201709929A (en) | 2015-06-12 | 2017-03-16 | 宏觀基因股份有限公司 | Combination therapy for the treatment of cancer |
UA124799C2 (en) | 2015-06-24 | 2021-11-24 | Янссен Байотек, Інк. | Immune modulation and treatment of solid tumors with antibodies that specifically bind cd38 |
AU2016285920A1 (en) | 2015-06-29 | 2018-02-01 | Bristol-Myers Squibb Company | Antibodies to CD40 with enhanced agonist activity |
KR20180040138A (en) | 2015-07-13 | 2018-04-19 | 싸이톰스 테라퓨틱스, 인크. | Anti-PD-1 antibodies, activatable anti-PD-1 antibodies, and methods of using them |
KR20180034588A (en) | 2015-07-30 | 2018-04-04 | 마크로제닉스, 인크. | PD-1-binding molecules and methods for their use |
US20190010231A1 (en) | 2015-08-07 | 2019-01-10 | Pieris Pharmaceuticals Gmbh | Novel fusion polypeptide specific for lag-3 and pd-1 |
EA201890630A1 (en) | 2015-09-01 | 2018-10-31 | Эйдженус Инк. | ANTIBODIES AGAINST PD-1 AND METHODS OF THEIR APPLICATION |
EA201890790A1 (en) | 2015-09-29 | 2018-10-31 | Селджин Корпорейшн | CONNECTING PD-1 PROTEINS AND METHODS OF THEIR APPLICATION |
CN109069622A (en) | 2015-09-30 | 2018-12-21 | 詹森生物科技公司 | Specifically bind the antagonistic antibodies and application method of people CD40 |
WO2017062619A2 (en) | 2015-10-08 | 2017-04-13 | Macrogenics, Inc. | Combination therapy for the treatment of cancer |
EP3371311B1 (en) | 2015-11-06 | 2021-07-21 | Orionis Biosciences BV | Bi-functional chimeric proteins and uses thereof |
AU2016356780A1 (en) | 2015-11-19 | 2018-06-28 | Bristol-Myers Squibb Company | Antibodies against glucocorticoid-induced tumor necrosis factor receptor (GITR) and uses thereof |
CR20180318A (en) | 2015-12-14 | 2018-09-19 | Macrogenics Inc | BISPECIFIC MOLECULES THAT HAVE IMMUNORREACTIVITY WITH PD-1 AND CTLA-4, AND METHODS OF USE OF THE SAME |
CN115554406A (en) | 2016-01-07 | 2023-01-03 | 博笛生物科技有限公司 | anti-CD 20 combinations for the treatment of tumors |
CN106943597A (en) | 2016-01-07 | 2017-07-14 | 博笛生物科技(北京)有限公司 | Anti-EGFR for treating tumour is combined |
CN115350279A (en) | 2016-01-07 | 2022-11-18 | 博笛生物科技有限公司 | anti-HER 2 combinations for the treatment of tumors |
JP7166923B2 (en) | 2016-02-05 | 2022-11-08 | オリオニス バイオサイエンシズ ビーブイ | Targeted therapeutic agents and their uses |
RU2018131123A (en) | 2016-02-17 | 2020-03-17 | Новартис Аг | ANTIBODIES TO TGF-BETA2 |
EA201891983A8 (en) | 2016-03-04 | 2020-05-28 | Бристол-Майерс Сквибб Компани | COMBINED THERAPY BY ANTIBODIES TO CD73 |
WO2017155981A1 (en) | 2016-03-07 | 2017-09-14 | Massachusetts Institute Of Technology | Protein-chaperoned t-cell vaccines |
TW201735949A (en) | 2016-03-24 | 2017-10-16 | 千禧製藥公司 | Methods of treating gastrointestinal immune-related adverse events in anti-CTLA4 anti-PD-1 combination treatments |
US11760803B2 (en) | 2016-03-24 | 2023-09-19 | Takeda Pharmaceutical Company Limited | Methods of treating gastrointestinal immune-related adverse events in immune oncology treatments |
MA44723A (en) | 2016-04-18 | 2019-02-27 | Celldex Therapeutics Inc | HUMAN CD40 BINDING AGONIST ANTIBODIES AND THEIR USES |
US11236141B2 (en) | 2016-05-13 | 2022-02-01 | Orionis Biosciences BV | Targeted mutant interferon-beta and uses thereof |
CN109563141A (en) | 2016-05-13 | 2019-04-02 | 奥里尼斯生物科学公司 | To the therapeutic targeting of cellular structures |
MX2018014387A (en) | 2016-05-27 | 2019-03-14 | Agenus Inc | Anti-tim-3 antibodies and methods of use thereof. |
US10994033B2 (en) | 2016-06-01 | 2021-05-04 | Bristol-Myers Squibb Company | Imaging methods using 18F-radiolabeled biologics |
JP7185530B2 (en) | 2016-06-13 | 2022-12-07 | トルク セラピューティクス, インコーポレイテッド | Methods and compositions for promoting immune cell function |
AU2017289270B2 (en) | 2016-06-27 | 2023-05-04 | The Regents Of The University Of California | Cancer treatment combinations |
JP7027401B2 (en) | 2016-07-14 | 2022-03-01 | ブリストル-マイヤーズ スクイブ カンパニー | Antibodies to TIM3 and its use |
US11090391B2 (en) | 2016-09-16 | 2021-08-17 | The Johns Hopkins University | Protein nanocages with enhanced mucus penetration for targeted tissue and intracellular delivery |
WO2018053405A1 (en) | 2016-09-19 | 2018-03-22 | Celgene Corporation | Methods of treating immune disorders using pd-1 binding proteins |
US10766958B2 (en) | 2016-09-19 | 2020-09-08 | Celgene Corporation | Methods of treating vitiligo using PD-1 binding antibodies |
RU2759334C2 (en) | 2016-09-21 | 2021-11-12 | Нексткьюр, Инк. | Antibodies against siglec-15 and their application methods |
TW202246349A (en) | 2016-10-11 | 2022-12-01 | 美商艾吉納斯公司 | Anti-lag-3 antibodies and methods of use thereof |
ES2917000T3 (en) | 2016-10-24 | 2022-07-06 | Orionis Biosciences BV | Target mutant interferon-gamma and uses thereof |
BR112019008426A2 (en) | 2016-11-02 | 2019-09-03 | Engmab Sarl | bispecific antibody against bcma and cd3 and an immunological drug for combined use in the treatment of multiple myeloma |
US11279694B2 (en) | 2016-11-18 | 2022-03-22 | Sumitomo Dainippon Pharma Oncology, Inc. | Alvocidib prodrugs and their use as protein kinase inhibitors |
WO2018098352A2 (en) | 2016-11-22 | 2018-05-31 | Jun Oishi | Targeting kras induced immune checkpoint expression |
MX2019006340A (en) | 2016-12-07 | 2019-11-07 | Agenus Inc | Anti-ctla-4 antibodies and methods of use thereof. |
CA3046082A1 (en) | 2016-12-07 | 2018-06-14 | Agenus Inc. | Antibodies and methods of use thereof |
KR20190103226A (en) | 2017-01-13 | 2019-09-04 | 아게누스 인코포레이티드 | T cell receptor that binds to NY-ESO-1 and methods of use thereof |
WO2018134279A1 (en) | 2017-01-18 | 2018-07-26 | Pieris Pharmaceuticals Gmbh | Novel fusion polypeptides specific for lag-3 and pd-1 |
EP3570870A1 (en) | 2017-01-20 | 2019-11-27 | Novartis AG | Combination therapy for the treatment of cancer |
WO2018144999A1 (en) | 2017-02-06 | 2018-08-09 | Orionis Biosciences, Inc. | Targeted engineered interferon and uses thereof |
WO2018141964A1 (en) | 2017-02-06 | 2018-08-09 | Orionis Biosciences Nv | Targeted chimeric proteins and uses thereof |
JP7161481B2 (en) | 2017-02-10 | 2022-10-26 | ノバルティス アーゲー | 1-(4-amino-5-bromo-6-(1H-pyrazol-1-yl)pyrimidin-2-yl)-1H-pyrazol-4-ol and its use in treating cancer |
BR112019017241A2 (en) | 2017-04-13 | 2020-04-14 | Agenus Inc | anti-cd137 antibodies and methods of using them |
CN108728444A (en) | 2017-04-18 | 2018-11-02 | 长春华普生物技术股份有限公司 | Immunoregulation polynucleotide and its application |
KR20190141223A (en) | 2017-04-26 | 2019-12-23 | 브리스톨-마이어스 스큅 컴퍼니 | Antibody Production Methods to Minimize Disulfide Bond Reduction |
CN108794467A (en) | 2017-04-27 | 2018-11-13 | 博笛生物科技有限公司 | 2- amino-quinoline derivatives |
EP3618863B1 (en) | 2017-05-01 | 2023-07-26 | Agenus Inc. | Anti-tigit antibodies and methods of use thereof |
CN110869392A (en) | 2017-05-16 | 2020-03-06 | 百时美施贵宝公司 | Treatment of cancer with anti-GITR agonistic antibodies |
AR111760A1 (en) | 2017-05-19 | 2019-08-14 | Novartis Ag | COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF SOLID TUMORS THROUGH INTRATUMORAL ADMINISTRATION |
KR20220167342A (en) | 2017-05-25 | 2022-12-20 | 브리스톨-마이어스 스큅 컴퍼니 | Antibodies comprising modified heavy constant regions |
JP2020522691A (en) | 2017-05-30 | 2020-07-30 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | Treatment of LAG-3-positive tumors |
KR20200010500A (en) | 2017-05-30 | 2020-01-30 | 브리스톨-마이어스 스큅 컴퍼니 | A composition comprising a combination of anti-LAG-3 antibodies, PD-1 pathway inhibitors, and immunotherapy agents |
CA3065304A1 (en) | 2017-05-30 | 2018-12-06 | Bristol-Myers Squibb Company | Compositions comprising an anti-lag-3 antibody or an anti-lag-3 antibody and an anti-pd-1 or anti-pd-l1 antibody |
JOP20190279A1 (en) | 2017-05-31 | 2019-11-28 | Novartis Ag | Crystalline forms of 5-bromo-2,6-di(1 h-pyrazol-1-yl)pyrimidin-4-amine and new salts |
WO2018229715A1 (en) | 2017-06-16 | 2018-12-20 | Novartis Ag | Compositions comprising anti-cd32b antibodies and methods of use thereof |
WO2018237173A1 (en) | 2017-06-22 | 2018-12-27 | Novartis Ag | Antibody molecules to cd73 and uses thereof |
JP7433910B2 (en) | 2017-06-22 | 2024-02-20 | ノバルティス アーゲー | Antibody molecules against CD73 and uses thereof |
BR112019027025A2 (en) | 2017-06-23 | 2020-06-30 | Birdie Biopharmaceuticals, Inc. | pharmaceutical compositions |
WO2019006007A1 (en) | 2017-06-27 | 2019-01-03 | Novartis Ag | Dosage regimens for anti-tim-3 antibodies and uses thereof |
WO2019003164A1 (en) | 2017-06-27 | 2019-01-03 | Neuracle Science Co., Ltd. | Use of anti-fam19a5 antibodies for treating cancers |
JP2020527572A (en) | 2017-07-20 | 2020-09-10 | ノバルティス アーゲー | Anti-LAG-3 antibody dosage regimen and its use |
JP7387585B2 (en) | 2017-09-04 | 2023-11-28 | アジェナス インコーポレイテッド | T-cell receptor that binds mixed lineage leukemia (MLL)-specific phosphopeptide and methods of use thereof |
EP3679070A1 (en) | 2017-09-07 | 2020-07-15 | Augusta University Research Institute, Inc. | Antibodies to programmed cell death protein 1 |
WO2019055579A1 (en) | 2017-09-12 | 2019-03-21 | Tolero Pharmaceuticals, Inc. | Treatment regimen for cancers that are insensitive to bcl-2 inhibitors using the mcl-1 inhibitor alvocidib |
WO2019075090A1 (en) | 2017-10-10 | 2019-04-18 | Tilos Therapeutics, Inc. | Anti-lap antibodies and uses thereof |
WO2019081983A1 (en) | 2017-10-25 | 2019-05-02 | Novartis Ag | Antibodies targeting cd32b and methods of use thereof |
WO2019089921A1 (en) | 2017-11-01 | 2019-05-09 | Bristol-Myers Squibb Company | Immunostimulatory agonistic antibodies for use in treating cancer |
JP2021503478A (en) | 2017-11-16 | 2021-02-12 | ノバルティス アーゲー | Combination treatment |
KR20200096253A (en) | 2017-11-30 | 2020-08-11 | 노파르티스 아게 | BCMA-targeting chimeric antigen receptor, and uses thereof |
US11946094B2 (en) | 2017-12-10 | 2024-04-02 | Augusta University Research Institute, Inc. | Combination therapies and methods of use thereof |
EP3732198A1 (en) | 2017-12-27 | 2020-11-04 | Bristol-Myers Squibb Company | Anti-cd40 antibodies and uses thereof |
US11324774B2 (en) | 2018-01-05 | 2022-05-10 | Augusta University Research Institute, Inc. | Compositions of oral alkaline salts and metabolic acid inducers and uses thereof |
CN112218651A (en) | 2018-01-08 | 2021-01-12 | 诺华公司 | Immunopotentiating RNA for combination with chimeric antigen receptor therapy |
CA3084370A1 (en) | 2018-01-12 | 2019-07-18 | Bristol-Myers Squibb Company | Combination therapy with anti-il-8 antibodies and anti-pd-1 antibodies for treating cancer |
JP7358361B2 (en) | 2018-01-12 | 2023-10-10 | ブリストル-マイヤーズ スクイブ カンパニー | Antibodies against TIM3 and their uses |
CA3096287A1 (en) | 2018-01-22 | 2019-07-25 | Pascal Biosciences Inc. | Cannabinoids and derivatives for promoting immunogenicity of tumor and infected cells |
WO2019147670A1 (en) | 2018-01-23 | 2019-08-01 | Nextcure, Inc. | B7-h4 antibodies and methods of use thereof |
US20210038659A1 (en) | 2018-01-31 | 2021-02-11 | Novartis Ag | Combination therapy using a chimeric antigen receptor |
MX2020008208A (en) | 2018-02-05 | 2020-11-09 | Orionis Biosciences Inc | Fibroblast binding agents and use thereof. |
US20200405806A1 (en) | 2018-02-08 | 2020-12-31 | Bristol-Myers Squibb Company | Combination of a tetanus toxoid, anti-ox40 antibody and/or anti-pd-1 antibody to treat tumors |
WO2019160956A1 (en) | 2018-02-13 | 2019-08-22 | Novartis Ag | Chimeric antigen receptor therapy in combination with il-15r and il15 |
US20210002373A1 (en) | 2018-03-01 | 2021-01-07 | Nextcure, Inc. | KLRG1 Binding Compositions and Methods of Use Thereof |
TW201945393A (en) | 2018-03-21 | 2019-12-01 | 美商戊瑞治療有限公司 | Antibodies binding to VISTA at acidic pH |
CA3096674A1 (en) | 2018-04-12 | 2019-10-17 | Bristol-Myers Squibb Company | Anticancer combination therapy with cd73 antagonist antibody and pd-1/pd-l1 axis antagonist antibody |
US20210147547A1 (en) | 2018-04-13 | 2021-05-20 | Novartis Ag | Dosage Regimens For Anti-Pd-L1 Antibodies And Uses Thereof |
MA52363A (en) | 2018-04-26 | 2021-03-03 | Agenus Inc | THERMAL SHOCK PROTEIN (HSP) PEPTIDIC COMPOSITIONS AND THEIR METHODS OF USE |
TW202015726A (en) | 2018-05-30 | 2020-05-01 | 瑞士商諾華公司 | Entpd2 antibodies, combination therapies, and methods of using the antibodies and combination therapies |
US20210214459A1 (en) | 2018-05-31 | 2021-07-15 | Novartis Ag | Antibody molecules to cd73 and uses thereof |
AU2019277029C1 (en) | 2018-06-01 | 2024-01-04 | Novartis Ag | Binding molecules against BCMA and uses thereof |
US20210221908A1 (en) | 2018-06-03 | 2021-07-22 | Lamkap Bio Beta Ltd. | Bispecific antibodies against ceacam5 and cd47 |
PE20211604A1 (en) | 2018-07-09 | 2021-08-23 | Five Prime Therapeutics Inc | ILT4 UNION ANTIBODIES |
TW202028235A (en) | 2018-07-11 | 2020-08-01 | 美商戊瑞治療有限公司 | Antibodies binding to vista at acidic ph |
AU2019301699B2 (en) | 2018-07-11 | 2023-11-02 | Actym Therapeutics, Inc. | Engineered immunostimulatory bacterial strains and uses thereof |
US20210277135A1 (en) | 2018-07-13 | 2021-09-09 | Bristol-Myers Squibb Company | Ox-40 agonist, pd-1 pathway inhibitor and ctla-4 inhibitor combination for use in a method of treating a cancer or a solid tumor |
AU2019306628A1 (en) | 2018-07-20 | 2021-02-11 | Surface Oncology, Inc. | Anti-CD112R compositions and methods |
WO2020021465A1 (en) | 2018-07-25 | 2020-01-30 | Advanced Accelerator Applications (Italy) S.R.L. | Method of treatment of neuroendocrine tumors |
WO2020021061A1 (en) | 2018-07-26 | 2020-01-30 | Pieris Pharmaceuticals Gmbh | Humanized anti-pd-1 antibodies and uses thereof |
BR112021000511A2 (en) | 2018-07-26 | 2021-04-06 | Bristol-Myers Squibb Company | LAG-3 COMBINATION THERAPY FOR CANCER TREATMENT |
AU2019328632A1 (en) | 2018-08-27 | 2021-03-25 | Pieris Pharmaceuticals Gmbh | Combination therapies comprising CD137/HER2 bispecific agents and PD-1 axis inhibitors and uses thereof |
US20210340279A1 (en) | 2018-08-31 | 2021-11-04 | Yale University | Compositions and methods of using cell-penetrating antibodies in combination with immune checkpoint modulators |
WO2020044252A1 (en) | 2018-08-31 | 2020-03-05 | Novartis Ag | Dosage regimes for anti-m-csf antibodies and uses thereof |
WO2020049534A1 (en) | 2018-09-07 | 2020-03-12 | Novartis Ag | Sting agonist and combination therapy thereof for the treatment of cancer |
WO2020061376A2 (en) | 2018-09-19 | 2020-03-26 | Alpine Immune Sciences, Inc. | Methods and uses of variant cd80 fusion proteins and related constructs |
JP2022504839A (en) | 2018-10-10 | 2022-01-13 | ティロス・セラピューティクス・インコーポレイテッド | Anti-LAP antibody mutants and their use |
EP3867409A1 (en) | 2018-10-16 | 2021-08-25 | Novartis AG | Tumor mutation burden alone or in combination with immune markers as biomarkers for predicting response to targeted therapy |
AU2019361124A1 (en) | 2018-10-19 | 2021-06-03 | Bristol-Myers Squibb Company | Combination therapy for melanoma |
CA3119341A1 (en) | 2018-11-16 | 2020-05-22 | Neoimmunetech, Inc. | Method of treating a tumor with a combination of il-7 protein and an immune checkpoint inhibitor |
JP2022513653A (en) | 2018-11-28 | 2022-02-09 | ブリストル-マイヤーズ スクイブ カンパニー | Antibodies containing modified heavy chain constant regions |
MX2021006544A (en) | 2018-12-04 | 2021-07-07 | Sumitomo Pharma Oncology Inc | Cdk9 inhibitors and polymorphs thereof for use as agents for treatment of cancer. |
CN109887035A (en) * | 2018-12-27 | 2019-06-14 | 哈尔滨理工大学 | Based on bat algorithm optimization BP neural network binocular vision calibration |
KR20210143718A (en) | 2019-01-17 | 2021-11-29 | 조지아 테크 리서치 코포레이션 | Drug Delivery Systems Containing Oxidized Cholesterol |
EP3924351A4 (en) | 2019-02-12 | 2022-12-21 | Sumitomo Pharma Oncology, Inc. | Formulations comprising heterocyclic protein kinase inhibitors |
MX2021009562A (en) | 2019-02-12 | 2021-09-08 | Novartis Ag | Pharmaceutical combination comprising tno155 and a pd-1 inhibitor. |
WO2020191326A1 (en) | 2019-03-20 | 2020-09-24 | Sumitomo Dainippon Pharma Oncology, Inc. | Treatment of acute myeloid leukemia (aml) with venetoclax failure |
AU2020245437A1 (en) | 2019-03-22 | 2021-09-30 | Sumitomo Pharma Oncology, Inc. | Compositions comprising PKM2 modulators and methods of treatment using the same |
EP3725370A1 (en) | 2019-04-19 | 2020-10-21 | ImmunoBrain Checkpoint, Inc. | Modified anti-pd-l1 antibodies and methods and uses for treating a neurodegenerative disease |
WO2020255009A2 (en) | 2019-06-18 | 2020-12-24 | Janssen Sciences Ireland Unlimited Company | Combination of hepatitis b virus (hbv) vaccines and anti-pd-1 antibody |
CN114630675A (en) | 2019-06-18 | 2022-06-14 | 爱尔兰詹森科学公司 | Combination of Hepatitis B Virus (HBV) vaccine and anti-PD-1 or anti-PD-L1 antibody |
WO2021003417A1 (en) | 2019-07-03 | 2021-01-07 | Sumitomo Dainippon Pharma Oncology, Inc. | Tyrosine kinase non-receptor 1 (tnk1) inhibitors and uses thereof |
WO2021024020A1 (en) | 2019-08-06 | 2021-02-11 | Astellas Pharma Inc. | Combination therapy involving antibodies against claudin 18.2 and immune checkpoint inhibitors for treatment of cancer |
US11680098B2 (en) | 2019-08-30 | 2023-06-20 | Agenus Inc. | Antibodies that specifically bind human CD96 |
JP2022548881A (en) | 2019-09-18 | 2022-11-22 | ノバルティス アーゲー | ENTPD2 Antibodies, Combination Therapy and Methods of Using Antibodies and Combination Therapy |
CN114786776A (en) | 2019-09-18 | 2022-07-22 | 拉姆卡普生物阿尔法股份公司 | Bispecific antibodies against CEACAM5 and CD3 |
TW202124446A (en) | 2019-09-18 | 2021-07-01 | 瑞士商諾華公司 | Combination therapies with entpd2 antibodies |
CA3149719A1 (en) | 2019-09-19 | 2021-03-25 | Bristol-Myers Squibb Company | Antibodies binding to vista at acidic ph |
CN114786679A (en) | 2019-10-21 | 2022-07-22 | 诺华股份有限公司 | Combination therapy with Vernetork and TIM-3 inhibitors |
MX2022004769A (en) | 2019-10-21 | 2022-05-16 | Novartis Ag | Tim-3 inhibitors and uses thereof. |
KR20220092540A (en) | 2019-10-29 | 2022-07-01 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | Combination of a PD-1 antagonist, a VEGFR/FGFR/RET tyrosine kinase inhibitor and a CBP/beta-catenin inhibitor for treating cancer |
US20220395553A1 (en) | 2019-11-14 | 2022-12-15 | Cohbar, Inc. | Cxcr4 antagonist peptides |
US20230000864A1 (en) | 2019-11-22 | 2023-01-05 | Sumitomo Pharma Oncology, Inc. | Solid dose pharmaceutical composition |
WO2021108025A1 (en) | 2019-11-26 | 2021-06-03 | Massachusetts Institute Of Technology | Cell-based cancer vaccines and cancer therapies |
EP3831849A1 (en) | 2019-12-02 | 2021-06-09 | LamKap Bio beta AG | Bispecific antibodies against ceacam5 and cd47 |
US11897950B2 (en) | 2019-12-06 | 2024-02-13 | Augusta University Research Institute, Inc. | Osteopontin monoclonal antibodies |
WO2021123996A1 (en) | 2019-12-20 | 2021-06-24 | Novartis Ag | Uses of anti-tgf-beta antibodies and checkpoint inhibitors for the treatment of proliferative diseases |
CN114980902A (en) | 2020-01-17 | 2022-08-30 | 诺华股份有限公司 | Combination comprising a TIM-3 inhibitor and a hypomethylated drug for the treatment of myelodysplastic syndrome or chronic myelomonocytic leukemia |
WO2021152548A1 (en) | 2020-01-30 | 2021-08-05 | Benitah Salvador Aznar | Combination therapy for treatment of cancer and cancer metastasis |
KR20220148846A (en) | 2020-02-28 | 2022-11-07 | 노파르티스 아게 | Triple Pharmaceutical Combination Comprising Dabrafenib, ERK Inhibitor, and RAF Inhibitor |
IL295979A (en) | 2020-03-06 | 2022-10-01 | Ona Therapeutics S L | Anti-cd36 antibodies and their use to treat cancer |
US20230140384A1 (en) | 2020-03-09 | 2023-05-04 | Bristol-Myers Squibb Company | Antibodies to cd40 with enhanced agonist activity |
US20230272056A1 (en) | 2020-04-09 | 2023-08-31 | Merck Sharp & Dohme Llc | Affinity matured anti-lap antibodies and uses thereof |
EP4138819A1 (en) | 2020-04-21 | 2023-03-01 | Novartis AG | Dosing regimen for treating a disease modulated by csf-1r |
AU2021270750A1 (en) | 2020-05-13 | 2022-12-08 | Massachusetts Institute Of Technology | Compositions of polymeric microdevices and their use in cancer immunotherapy |
WO2021231732A1 (en) | 2020-05-15 | 2021-11-18 | Bristol-Myers Squibb Company | Antibodies to garp |
US11767353B2 (en) | 2020-06-05 | 2023-09-26 | Theraly Fibrosis, Inc. | Trail compositions with reduced immunogenicity |
CA3182579A1 (en) | 2020-07-07 | 2022-01-13 | Ugur Sahin | Therapeutic rna for hpv-positive cancer |
WO2022009157A1 (en) | 2020-07-10 | 2022-01-13 | Novartis Ag | Lhc165 and spartalizumab combinations for treating solid tumors |
CN116194480A (en) | 2020-08-13 | 2023-05-30 | 百时美施贵宝公司 | Method for redirecting IL-2 to target cells of interest |
WO2022043557A1 (en) | 2020-08-31 | 2022-03-03 | Advanced Accelerator Applications International Sa | Method of treating psma-expressing cancers |
WO2022043558A1 (en) | 2020-08-31 | 2022-03-03 | Advanced Accelerator Applications International Sa | Method of treating psma-expressing cancers |
WO2022097060A1 (en) | 2020-11-06 | 2022-05-12 | Novartis Ag | Cd19 binding molecules and uses thereof |
TW202237119A (en) | 2020-12-10 | 2022-10-01 | 美商住友製藥腫瘤公司 | Alk-5 inhibitors and uses thereof |
EP4055055B1 (en) | 2020-12-18 | 2023-11-22 | LamKap Bio beta AG | Bispecific antibodies against ceacam5 and cd47 |
WO2022135666A1 (en) | 2020-12-21 | 2022-06-30 | BioNTech SE | Treatment schedule for cytokine proteins |
TW202245808A (en) | 2020-12-21 | 2022-12-01 | 德商拜恩迪克公司 | Therapeutic rna for treating cancer |
WO2022135667A1 (en) | 2020-12-21 | 2022-06-30 | BioNTech SE | Therapeutic rna for treating cancer |
JP2024505049A (en) | 2021-01-29 | 2024-02-02 | ノバルティス アーゲー | Administration modes for anti-CD73 and anti-ENTPD2 antibodies and their uses |
WO2022165260A1 (en) | 2021-01-29 | 2022-08-04 | Iovance Biotherapeutics, Inc. | Methods of making modified tumor infiltrating lymphocytes and their use in adoptive cell therapy |
WO2022165403A1 (en) | 2021-02-01 | 2022-08-04 | Yale University | Chemotherapeutic bioadhesive particles with immunostimulatory molecules for cancer treatment |
TW202304506A (en) | 2021-03-25 | 2023-02-01 | 日商安斯泰來製藥公司 | Combination therapy involving antibodies against claudin 18.2 for treatment of cancer |
TW202304979A (en) | 2021-04-07 | 2023-02-01 | 瑞士商諾華公司 | USES OF ANTI-TGFβ ANTIBODIES AND OTHER THERAPEUTIC AGENTS FOR THE TREATMENT OF PROLIFERATIVE DISEASES |
TW202309022A (en) | 2021-04-13 | 2023-03-01 | 美商努法倫特公司 | Amino-substituted heterocycles for treating cancers with egfr mutations |
WO2022256538A1 (en) | 2021-06-03 | 2022-12-08 | Synthorx, Inc. | Head and neck cancer combination therapy comprising an il-2 conjugate and cetuximab |
AU2022312698A1 (en) | 2021-07-13 | 2024-01-25 | BioNTech SE | Multispecific binding agents against cd40 and cd137 in combination therapy for cancer |
WO2023007472A1 (en) | 2021-07-30 | 2023-02-02 | ONA Therapeutics S.L. | Anti-cd36 antibodies and their use to treat cancer |
WO2023051926A1 (en) | 2021-09-30 | 2023-04-06 | BioNTech SE | Treatment involving non-immunogenic rna for antigen vaccination and pd-1 axis binding antagonists |
WO2023057534A1 (en) | 2021-10-06 | 2023-04-13 | Genmab A/S | Multispecific binding agents against pd-l1 and cd137 in combination |
TW202333802A (en) | 2021-10-11 | 2023-09-01 | 德商拜恩迪克公司 | Therapeutic rna for lung cancer |
CA3234821A1 (en) | 2021-10-28 | 2023-05-04 | Suman Kumar VODNALA | Methods for culturing immune cells |
WO2023083439A1 (en) | 2021-11-09 | 2023-05-19 | BioNTech SE | Tlr7 agonist and combinations for cancer treatment |
WO2023122573A1 (en) | 2021-12-20 | 2023-06-29 | Synthorx, Inc. | Head and neck cancer combination therapy comprising an il-2 conjugate and pembrolizumab |
WO2023147488A1 (en) | 2022-01-28 | 2023-08-03 | Iovance Biotherapeutics, Inc. | Cytokine associated tumor infiltrating lymphocytes compositions and methods |
WO2023170606A1 (en) | 2022-03-08 | 2023-09-14 | Alentis Therapeutics Ag | Use of anti-claudin-1 antibodies to increase t cell availability |
EP4249498A1 (en) * | 2022-03-23 | 2023-09-27 | Lipotrue, S.L. | Peptides and compositions for use in cosmetics, food and medicine |
WO2023192478A1 (en) | 2022-04-01 | 2023-10-05 | Bristol-Myers Squibb Company | Combination therapy with anti-il-8 antibodies and anti-pd-1 antibodies for treating cancer |
WO2023218046A1 (en) | 2022-05-12 | 2023-11-16 | Genmab A/S | Binding agents capable of binding to cd27 in combination therapy |
WO2023230554A1 (en) | 2022-05-25 | 2023-11-30 | Pfizer Inc. | Combination of a braf inhibitor, an egfr inhibitor, and a pd-1 antagonist for the treatment of braf v600e-mutant, msi-h/dmmr colorectal cancer |
WO2023242351A1 (en) | 2022-06-16 | 2023-12-21 | Lamkap Bio Beta Ag | Combination therapy of bispecific antibodies against ceacam5 and cd47 and bispecific antibodies against ceacam5 and cd3 |
WO2024040264A1 (en) | 2022-08-19 | 2024-02-22 | Massachusetts Institute Of Technology | Compositions and methods for targeting dendritic cell lectins |
WO2024069009A1 (en) | 2022-09-30 | 2024-04-04 | Alentis Therapeutics Ag | Treatment of drug-resistant hepatocellular carcinoma |
WO2024081736A2 (en) | 2022-10-11 | 2024-04-18 | Yale University | Compositions and methods of using cell-penetrating antibodies |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
US4965188A (en) | 1986-08-22 | 1990-10-23 | Cetus Corporation | Process for amplifying, detecting, and/or cloning nucleic acid sequences using a thermostable enzyme |
US4683195A (en) | 1986-01-30 | 1987-07-28 | Cetus Corporation | Process for amplifying, detecting, and/or-cloning nucleic acid sequences |
US5618920A (en) * | 1985-11-01 | 1997-04-08 | Xoma Corporation | Modular assembly of antibody genes, antibodies prepared thereby and use |
US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
US5530101A (en) * | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
GB8928874D0 (en) * | 1989-12-21 | 1990-02-28 | Celltech Ltd | Humanised antibodies |
DE69433087T2 (en) | 1993-06-11 | 2004-06-09 | Coulter International Corp., Miami | ANTI-CD3 ANTIBODY AMINODEXTRAN CONJUGATES FOR INDUCTION OF T CELL ACTIVATION AND PROPAGATION |
IL108501A (en) * | 1994-01-31 | 1998-10-30 | Mor Research Applic Ltd | Antibodies and pharmaceutical compositions containing them |
GB9416657D0 (en) | 1994-08-17 | 1994-10-12 | Biocine Spa | T cell activation |
GB9501079D0 (en) | 1995-01-19 | 1995-03-08 | Bioinvent Int Ab | Activation of T-cells |
IL129299A0 (en) | 1999-03-31 | 2000-02-17 | Mor Research Applic Ltd | Monoclonal antibodies antigens and diagnosis of malignant diseases |
IL145926A0 (en) * | 2001-10-15 | 2002-07-25 | Mor Research Applic Ltd | Peptide epitopes of mimotopes useful in immunomodulation |
-
2002
- 2002-05-23 IL IL14982002A patent/IL149820A0/en unknown
-
2003
- 2003-05-22 HU HUE03723038A patent/HUE025710T2/en unknown
- 2003-05-22 WO PCT/IL2003/000425 patent/WO2003099196A2/en active Application Filing
- 2003-05-22 KR KR1020047018962A patent/KR101169254B1/en active IP Right Grant
- 2003-05-22 DK DK03723038.0T patent/DK1575484T3/en active
- 2003-05-22 AU AU2003230183A patent/AU2003230183B2/en not_active Ceased
- 2003-05-22 EP EP03723038.0A patent/EP1575484B1/en not_active Expired - Lifetime
- 2003-05-22 CA CA2487060A patent/CA2487060C/en not_active Expired - Fee Related
- 2003-05-22 PT PT37230380T patent/PT1575484E/en unknown
- 2003-05-22 ES ES03723038.0T patent/ES2549303T3/en not_active Expired - Lifetime
- 2003-05-22 JP JP2004506723A patent/JP4764627B2/en not_active Expired - Fee Related
- 2003-05-22 SI SI200332448T patent/SI1575484T1/en unknown
-
2004
- 2004-11-14 IL IL165193A patent/IL165193A/en active IP Right Grant
- 2004-11-19 US US10/994,091 patent/US7332582B2/en not_active Expired - Lifetime
-
2007
- 2007-09-12 US US11/854,160 patent/US7524498B2/en not_active Expired - Lifetime
-
2009
- 2009-03-18 US US12/406,492 patent/US7981416B2/en not_active Expired - Lifetime
-
2010
- 2010-09-05 IL IL207985A patent/IL207985A/en active IP Right Grant
-
2011
- 2011-02-25 JP JP2011039339A patent/JP2011139708A/en not_active Abandoned
-
2015
- 2015-10-07 CY CY20151100903T patent/CY1117114T1/en unknown
Also Published As
Publication number | Publication date |
---|---|
US7332582B2 (en) | 2008-02-19 |
AU2003230183B2 (en) | 2009-01-22 |
ES2549303T3 (en) | 2015-10-26 |
IL207985A0 (en) | 2010-12-30 |
JP4764627B2 (en) | 2011-09-07 |
PT1575484E (en) | 2015-11-02 |
EP1575484A4 (en) | 2006-11-22 |
CY1117114T1 (en) | 2017-04-05 |
AU2003230183A1 (en) | 2003-12-12 |
IL165193A0 (en) | 2005-12-18 |
US7981416B2 (en) | 2011-07-19 |
WO2003099196A2 (en) | 2003-12-04 |
DK1575484T3 (en) | 2015-10-12 |
US20090263386A1 (en) | 2009-10-22 |
HUE025710T2 (en) | 2016-04-28 |
EP1575484B1 (en) | 2015-07-08 |
IL149820A0 (en) | 2002-11-10 |
KR101169254B1 (en) | 2012-08-03 |
EP1575484A2 (en) | 2005-09-21 |
JP2006505244A (en) | 2006-02-16 |
JP2011139708A (en) | 2011-07-21 |
SI1575484T1 (en) | 2015-11-30 |
KR20050008736A (en) | 2005-01-21 |
US7524498B2 (en) | 2009-04-28 |
WO2003099196A3 (en) | 2005-07-28 |
US20050180969A1 (en) | 2005-08-18 |
IL207985A (en) | 2013-10-31 |
CA2487060C (en) | 2011-01-04 |
IL165193A (en) | 2010-12-30 |
US20080025980A1 (en) | 2008-01-31 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CA2487060A1 (en) | Humanized immunomodulatory monoclonal antibodies for the treatment of neoplastic disease or immunodeficiency | |
US11136413B2 (en) | PDL-1 antibody, pharmaceutical composition thereof, and uses thereof | |
KR102340832B1 (en) | Anti-PD-1 antibodies and uses thereof | |
CN110799539B (en) | Anti-4-1 BB antibodies and methods of making and using the same | |
CN112794909B (en) | anti-TIGIT monoclonal antibody and application thereof | |
CN110291109A (en) | The monoclonal antibody and its segment of people's programmed death receptor PD-1 | |
JP2014518640A (en) | Human antigen binding protein that binds to complex comprising β-croto and FGF receptor | |
JP2006505244A5 (en) | ||
US10759859B2 (en) | Anti-PD-1 antibodies and uses thereof | |
CN114728065A (en) | Antibodies to CD3 and BCMA and bispecific binding proteins prepared therefrom | |
CN115991778A (en) | anti-PD-L1 antibodies and uses thereof | |
JP2019514871A (en) | Methods of administration of bispecific constructs that bind CD33 and CD3 for use in a method of treating myeloid leukemia | |
Akbari et al. | Design, expression and evaluation of a novel humanized single chain antibody against epidermal growth factor receptor (EGFR) | |
WO2023186000A1 (en) | Bispecific antibody and application thereof | |
CN113150156B (en) | anti-TIGIT antibodies and uses thereof | |
CN115925917A (en) | anti-PVRIG protein antibodies or antibody fragments and uses thereof | |
WO2022068854A1 (en) | Antibodies targeting human claudin 18.2 and uses thereof | |
WO2023093744A1 (en) | Bispecific antigen binding protein | |
WO2024077777A1 (en) | Multifunctional recombinant antibody, and preparation method and use therefor | |
US20210079087A1 (en) | Treatment of autoimmune and inflammatory disorders using antibodies that bind interleukin-17a (il-17a) | |
WO2018126595A1 (en) | Antibody or antibody fragment capable of binding to lung-specific x protein and use thereof | |
TW202246340A (en) | Anti-CTLA-4 antibody and use thereof | |
CN116848144A (en) | anti-PD-L1 antibodies and uses thereof | |
KR20240049331A (en) | Antibodies to human CD16a and variants thereof | |
CN117024592A (en) | anti-B7H 3 antibodies and uses thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
EEER | Examination request | ||
MKLA | Lapsed |
Effective date: 20200831 |