[go: up one dir, main page]

WO1998016245A1 - Procede de determination d'un auto-anticorps - Google Patents

Procede de determination d'un auto-anticorps Download PDF

Info

Publication number
WO1998016245A1
WO1998016245A1 PCT/JP1997/001259 JP9701259W WO9816245A1 WO 1998016245 A1 WO1998016245 A1 WO 1998016245A1 JP 9701259 W JP9701259 W JP 9701259W WO 9816245 A1 WO9816245 A1 WO 9816245A1
Authority
WO
WIPO (PCT)
Prior art keywords
peptide
amino acid
fragment
antibody
acid sequence
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.)
Ceased
Application number
PCT/JP1997/001259
Other languages
English (en)
Japanese (ja)
Inventor
Tomohiko Taminato
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shionogi and Co Ltd
Original Assignee
Shionogi and Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Shionogi and Co Ltd filed Critical Shionogi and Co Ltd
Priority to JP51816398A priority Critical patent/JP4233608B2/ja
Publication of WO1998016245A1 publication Critical patent/WO1998016245A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70596—Molecules with a "CD"-designation not provided for elsewhere
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/564—Immunoassay; Biospecific binding assay; Materials therefor for pre-existing immune complex or autoimmune disease, i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants

Definitions

  • the present invention relates to a method for measuring an anti-CD38 autoantibody using a CD38 peptide fragment, and a pharmaceutical composition for treating an autoimmune disease, comprising a GD38 peptide, a fragment thereof and a mutant thereof.
  • IDDM Insulin-dependent diabetes mellitus
  • autoimmune inflammation Kernee insulitis
  • ⁇ Cells that secrete cells are destroyed, resulting in a severe lack of insulin. Therefore, as the fundamental treatment of IDDM and insulitis, it is necessary to carry out pre-onset treatment, early treatment, that is, treatment before tunnel cells are destroyed, and an early diagnosis method is important.
  • early treatment that is, treatment before tunnel cells are destroyed, and an early diagnosis method is important.
  • the only methods currently in use are post-mortem or post-morbid diagnosis by pathological dissection or biopsy, at which point insulin-producing cells have already been destroyed.
  • CD38 is a glycoprotein with a molecular weight of 46 kDa, mainly found on the surface of lymphocytes, and as a marker for T cell and B cell differentiation and activation.
  • the malignancy (youngness) of T cells and B cells It is used as an indicator for Recently, Northern blot analysis using the cDNA of the CD38 molecule as a probe and immunohistochemical staining using a specific antibody against the GD38 molecule have revealed that CD38 is not limited to leukocytes and immune cells, but also to the rat brain, duodenum, heart, and pituitary gland. It was also confirmed that it was expressed in Knee Island.
  • cADPR cyclic ADP-ribose
  • CD38 is a membrane-bound protein and its soluble portion is thought to flow out into the blood and express its function. Therefore, anti-CD38 antibody-positive serum was measured using three peptide fragments, which are extracellular from the amino acid sequence of CD38 and are presumed to be involved in the regulation of function. The peptide at the end (SEQ ID NO: 1) shows the strongest anti-J center.
  • the present inventors have found that GD38 immunoreactivity is localized at the cell periphery (probably on the cell surface) in knee island cells, and that insulin secretion is significantly suppressed by treatment with a commercially available anti-CD38 monoclonal antibody.
  • anti-CD38 antibody When the presence of anti-CD38 antibody was examined in diabetic patients, it was detected in about 68% of the sera of IDDM patients. In addition, anti-CD38 antibodies were detected in 50-70% of the NOD mice, which have been established as the best model animals for IDDM, after 7 weeks of age when autoimmune inflammation occurred in the knee island. . Thus, it was found that autoantibodies against CD38 appeared in the blood of humans and model animals.
  • This antibody itself suppresses insulin secretion, and at the same time, is considered to have a significance as a marker that indicates that Sesui inflammation occurs in Knee island and cell destruction is progressing. Therefore, since anti-CD38 antibody is deeply involved in the insulin secretion mechanism, it is considered that measurement of anti-CD38 antibody can contribute to the prediction of IDDM and knee insulitis.
  • CD38 may play an important role in regulating and controlling insulin secretion.
  • a measurement system for anti-CD38 autoantibodies in the serum of diabetic patients was established using the C-terminal peptide of CD38, and the relationship between anti-CD38 autoantibodies and the mechanism of diabetes development was analyzed. Based on results.
  • the present invention relates to a method for measuring an anti-CD38 autoantibody using a CD38 peptide fragment, a pharmaceutical composition for treating an autoimmune disease using a GD38 peptide fragment, and a peptide having the amino acid sequence of SEQ ID NO: 1. .
  • the present invention relates to a CD38 peptide fragment, preferably in the extracellular region of a CD38 peptide. 10-30 Peptide fragment comprising an amino acid residue, more preferably a peptide comprising an amino acid sequence of SEQ ID NO: 1 or its amino acid sequence, substitution or deletion of one or several amino acid residues
  • the present invention relates to a method for measuring an anti-CD38 autoantibody using a peptide having at least one mutation selected from among insertion, addition and addition.
  • a competition method, a Sandwich method or the like can be used.
  • a CD38 peptide fragment is immobilized on a microtiter plate by the avidin-biotin method or the like, and a sample obtained from a patient, such as serum or plasma, is added to an anti-CD38 antibody labeled with peroxidase or alkaline phosphatase.
  • the antibody is reacted, and a corresponding substrate, for example, orthophenylenediamine or tetramethylbenzidine, or 4-nitrophenyl phosphate is added. After performing a color reaction, the absorbance is measured.
  • the peptide fragment of the present invention or a mutant thereof is based on the amino acid sequence of human CD38 (Jackson DG., Bel I Jl., J Immono !. 144, 2811-2815, 1990). It can be chemically synthesized by a one-field solid-phase synthesis method (Merrifield, RB, J. Am. Chem. Soc., 85, 2149-2156 (1963)).
  • the present invention further provides a pharmaceutical composition for treating an autoimmune disease, comprising a CD38 peptide, a peptide fragment thereof, or a variant thereof, which may be chemically modified, particularly wherein the autoimmune disease is
  • the composition relates to diabetes.
  • “Chemical modification” means any modification made to protect a peptide from degradation by various proteases present in the body when administering the peptide as a therapeutic agent, typically polyethylene glycol (PEG). Means to modify the peptide with. For example, when a peptide is administered as a therapeutic agent, it may be degraded by various proteases present in the living body. Therefore, when a peptide is administered as a therapeutic drug, its effect cannot be expected unless it is administered in large amounts, but it must be avoided because of its effects on the living body. Therefore, if administered in a form that is not easily affected by proteases and the like, a small amount and an effective concentration can be maintained for a longer time.
  • PEG polyethylene glycol
  • the peptide fragment of the CD38 peptide is a peptide having 5 or more amino acid residues arbitrarily selected from the amino acid sequence of SEQ ID NO: 2, and preferably a peptide containing an extracellular region.
  • a peptide containing the antigenic site of the autoantibody is preferferably a peptide containing the antigenic site of the autoantibody
  • Mutants of CD38 peptide or its peptide fragment are selected from substitution, deletion, insertion and addition of one or several amino acids in the amino acid sequence of CD38 peptide or its peptide fragment. It means a peptide with at least one mutation. Methods for producing such peptides and their mutants are described in Molecular Cloning A Laboratory Manual, 2nd edition, An Latt ats, T. et al, Gold Spring Harbor Laboratories (New York), (1989)). Have been.
  • Insulin-dependent diabetes mellitus is an autoimmune disease caused by an autoimmune reaction in the knee, which causes destruction of S cells and reduced insulin secretion function.
  • a treatment method for self-immune disease in which no immune response is caused by self-antigen administration, that is, immunosuppression specific to antigens by inducing “immune tolerance” to prevent onset.
  • the CD38 peptides, fragments and variants thereof of the present invention can be used for the treatment of IDDM, an autoimmune disease. These can also be expected to neutralize the autoantibody attack on the island.
  • various factors such as the amount of the antigen, the route of administration, and the form of the antigen are related to the method of administering the autoantigen protein, the antigen peptide and the like.
  • the application to treatment in particular is being considered for the induction of “tolerance” by oral administration.
  • Immune tolerance that occurs when an antigen is taken orally is called "oral tolerance,” and oral administration is considered to be useful as a treatment method for autoimmune diseases in which the causative antigen is clear. It has been reported that oral administration of collagen, the causative antigen, in rheumatoid arthritis, an autoimmune disease, suppressed the development of arthritis, and clinical application has been attempted.
  • CD38 peptide, its peptide fragment or a mutant thereof is orally administered before or early onset of DM and knee insulitis, and antigen by oral tolerance is administered. If the usefulness of specific immunosuppression is demonstrated, the burden on patients will be greatly reduced, and it can be expected to become a revolutionary therapeutic agent.
  • the CD38 peptide, the peptide fragment or the mutant thereof used in the therapeutic pharmaceutical composition of the present invention may be prepared by genetic engineering.
  • the present invention further relates to a therapeutic pharmaceutical composition selected from dosage forms that can be administered orally, nasally, intravenously, intraperitoneally, and intrathymus.
  • a usual dosage form for example, a solid preparation such as a tablet, a powder, a granule, a capsule, etc .; a liquid preparation; an oily suspension; Liquid or elixirs; aqueous or oily injection suspensions; and the like.
  • a carrier such as a conventional excipient, a binder, a water solvent, an oily solvent, an emulsifier, a suspending agent, and the like can be used for the preparation thereof, if necessary.
  • Agents for example, those containing a preservative, a stabilizer and the like.
  • FIG. 1 is a graph showing the effect of an anti-GD38 antibody on insulin release.
  • Method (1) In 6 cells (insulin-secreting cell line derived from knee cells): Min 6 cells were cultured in 10% FCS DEM (Glucose 20 mM).
  • Anti-CD38 antibody anti-GD38 monoclonal antibody (T10; mouse lgG1), and two types of CD38 peptide fragments 287-297 (N-Cys Va I Lys Asn Pro 6lu Asp Ser Ser Cys Thr-C: 287-Ag) and 241-255 (N-Cys Ser Asn Asn Pro Va I Ser Val Phe Trp Lys Thr Va I Ser Arg-C; 241 -Ag) were conjugated to Keyhole Limpet Hemocyanine, respectively, and immunized rabbits. The polyclonal antibody prepared as described above was used.
  • Insulin secretion Min 6 cells were cultured in 48-well plates, and a KRB buffer supplemented with 10 / oFGS was used as a medium during secretion experiments. An anti-CD38 antibody, D-glucose (5, 20 mM), and various insulin secretion stimulating substances were added thereto, and insulin secreted into the culture solution for 30 minutes was measured by RIA.
  • the peptide 287-Ag described in SEQ ID NO: 1 was used as an antigen, and was adsorbed and immobilized on a 96-well plate for EIA, followed by blocking with BSA for 24 hours and used for measurement. Serum from human, rat, mouse, etc. was used as a sample. Add the serum sample to the antigen-coated 96-well microplate prepared above, and react gently with gentle shaking at room temperature for about 60 minutes. Discard the serum sample, wash well, and add the biotinylated secondary antibody solution.
  • biotinylated secondary antibody a biotinylated anti-human IgG is used when the serum sample is human, and a biotinylated anti-rat IgG and a biotinylated anti-mouse IgG are used for rat and mouse, respectively. Shake gently at room temperature for about 60 minutes, and then wash thoroughly. Then add avidin-DH and biotinylated peroxidase or biotinylated alkaline phosphatase and gently shake for about 30 minutes at room temperature. Discard the ABC reagent, add PBS at 100 ml / wel I at a time, shake gently for about 5 minutes, and wash thoroughly.
  • Substrates orthophenylenediamine (0P), tetramethylbenzidine (TMB), 4-ditrophenylphosphate or 2,2'-azino-bis (1-ethylbenzothiazoline-6-sulfonic acid) (ABTS), etc.
  • TMB tetramethylbenzidine
  • ABTS 2,2'-azino-bis (1-ethylbenzothiazoline-6-sulfonic acid)
  • anti-CD38 antibody was measured using 1 ⁇ 0 diabetic patient sera. As a result, 22 out of 32 cases (68%) were positive in IDDM, In non-insulin dependent diabetes mellitus (NIDDM), only 16 of 128 (12.5%) were positive.
  • the positive rate was 84% after the 7th week of age when autoimmune inflammation (knee insulitis) occurred in Tengdo. Diabetes develops after 11 weeks of age in this mouse system. In addition, all cases were negative at the 5th week of age when knee island disease had not yet occurred.
  • anti-CD38 antibody Since anti-CD38 antibody is detected before the onset of diabetes and at the same time as the onset of knee insulitis, it is considered to be useful for predicting the onset of diabetes and to contribute to the early treatment of insulin-dependent diabetes and its prevention.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Chemical & Material Sciences (AREA)
  • Hematology (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Biochemistry (AREA)
  • Cell Biology (AREA)
  • Biomedical Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Urology & Nephrology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Zoology (AREA)
  • Microbiology (AREA)
  • Analytical Chemistry (AREA)
  • Biotechnology (AREA)
  • Rheumatology (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Toxicology (AREA)
  • Food Science & Technology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Rehabilitation Therapy (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Procédé servant à déterminer un auto-anticorps anti-CD38 au moyen de fragments de peptides de CD38, ce qui permet de diagnostiquer le diabète avant sa déclaration ou à un stade précoce; peptide de CD38, ses fragments et ses variantes; ses produits de modification chimique; ses produits obtenus par des opérations de génie génétique; compositions médicamenteuses préparées au moyen de ce procédé afin de soigner des maladies auto-immunes, particulièrement l'insulite lymphocytaire et le diabète; composition médicamenteuse s'administrant par voie orale et préparée au moyen de ce procédé.
PCT/JP1997/001259 1996-10-15 1997-04-11 Procede de determination d'un auto-anticorps Ceased WO1998016245A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP51816398A JP4233608B2 (ja) 1996-10-15 1997-04-11 自己抗体測定方法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP8/272537 1996-10-15
JP27253796 1996-10-15

Publications (1)

Publication Number Publication Date
WO1998016245A1 true WO1998016245A1 (fr) 1998-04-23

Family

ID=17515282

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1997/001259 Ceased WO1998016245A1 (fr) 1996-10-15 1997-04-11 Procede de determination d'un auto-anticorps

Country Status (2)

Country Link
JP (1) JP4233608B2 (fr)
WO (1) WO1998016245A1 (fr)

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU764738B2 (en) * 1999-08-25 2003-08-28 Alkermes, Inc. Use of simple amino acids to form porous particles
US7829673B2 (en) 2005-03-23 2010-11-09 Genmab A/S Antibodies against CD38 for treatment of multiple myeloma
US9040050B2 (en) 2006-09-26 2015-05-26 Genmab A/S Combination treatment of CD38-expressing tumors
US9249226B2 (en) 2010-06-09 2016-02-02 Genmab A/S Antibodies against human CD38
CN106434683A (zh) * 2005-10-12 2017-02-22 莫佛塞斯公司 特异性针对人CD38的完全人HuCAL GOLD‑衍生治疗抗体的生成和鉴定
US9603927B2 (en) 2014-02-28 2017-03-28 Janssen Biotech, Inc. Combination therapies with anti-CD38 antibodies
US9732154B2 (en) 2014-02-28 2017-08-15 Janssen Biotech, Inc. Anti-CD38 antibodies for treatment of acute lymphoblastic leukemia
US10385135B2 (en) 2015-11-03 2019-08-20 Janssen Biotech, Inc. Subcutaneous formulations of anti-CD38 antibodies and their uses
US10604580B2 (en) 2014-09-09 2020-03-31 Janssen Biotech, Inc. Combination therapies with anti-CD38 antibodies
US10668149B2 (en) 2015-06-22 2020-06-02 Janssen Biotech, Inc. Combination therapies for heme malignancies with anti-CD38 antibodies and survivin inhibitors
US10766965B2 (en) 2015-05-20 2020-09-08 Janssen Biotech, Inc. Anti-CD38 antibodies for treatment of light chain amyloidosis and other CD38-positive hematological malignancies
US10781261B2 (en) 2015-11-03 2020-09-22 Janssen Biotech, Inc. Subcutaneous formulations of anti-CD38 antibodies and their uses
US10793630B2 (en) 2014-12-04 2020-10-06 Janssen Biotech, Inc. Anti-CD38 antibodies for treatment of acute myeloid leukemia
US11021543B2 (en) 2015-06-24 2021-06-01 Janssen Biotech, Inc. Immune modulation and treatment of solid tumors with antibodies that specifically bind CD38
US11618787B2 (en) 2017-10-31 2023-04-04 Janssen Biotech, Inc. Methods of treating high risk multiple myeloma

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
THE JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, Vol. 270, No. 50, KATO ICHIRO et al., "Regulatory Role of CD38 (ADP-Ribosyl Cyclase/Cyclic ADP-Ribose Hydrolase) in Insulin Secretion by Glucose in Pancreatic Beta Cells", pages 30045-30050. *
THE JOURNAL OF IMMUNOLOGY, 1990, Vol. 144, No. 7, JACKSON DAVID G. et al., "Isolation of a cDNA Encoding the Human CD38(T10) Molecule, A Cell Surface Glycoprotein With an Unusual Discontinuous Pattern of Expression During Lymphocyte Differentian", pages 2811-2815. *

Cited By (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU764738B2 (en) * 1999-08-25 2003-08-28 Alkermes, Inc. Use of simple amino acids to form porous particles
US7829673B2 (en) 2005-03-23 2010-11-09 Genmab A/S Antibodies against CD38 for treatment of multiple myeloma
US9187565B2 (en) 2005-03-23 2015-11-17 Genmab A/S Antibodies against CD38 for treatment of multiple myeloma
CN106434683B (zh) * 2005-10-12 2020-03-13 莫佛塞斯公司 特异性针对人CD38的完全人HuCAL GOLD-衍生治疗抗体的生成和鉴定
CN106434683A (zh) * 2005-10-12 2017-02-22 莫佛塞斯公司 特异性针对人CD38的完全人HuCAL GOLD‑衍生治疗抗体的生成和鉴定
US9040050B2 (en) 2006-09-26 2015-05-26 Genmab A/S Combination treatment of CD38-expressing tumors
US9944711B2 (en) 2010-06-09 2018-04-17 Genmab A/S Antibodies against human CD38
US11230604B2 (en) 2010-06-09 2022-01-25 Genmab A/S Antibodies against human CD38
US9249226B2 (en) 2010-06-09 2016-02-02 Genmab A/S Antibodies against human CD38
US9732154B2 (en) 2014-02-28 2017-08-15 Janssen Biotech, Inc. Anti-CD38 antibodies for treatment of acute lymphoblastic leukemia
US10556961B2 (en) 2014-02-28 2020-02-11 Janssen Biotech, Inc. Anti-CD38 antibodies for treatment of acute lymphoblastic leukemia
US9603927B2 (en) 2014-02-28 2017-03-28 Janssen Biotech, Inc. Combination therapies with anti-CD38 antibodies
US12060432B2 (en) 2014-02-28 2024-08-13 Janssen Biotech, Inc. Combination therapies with anti-CD38 antibodies
US11713355B2 (en) 2014-02-28 2023-08-01 Janssen Biotech, Inc. Anti-CD38 antibodies for treatment of acute lymphoblastic leukemia
US10800851B2 (en) 2014-02-28 2020-10-13 Janssen Biotech, Inc. Combination therapies with anti-CD38 antibodies
US10604580B2 (en) 2014-09-09 2020-03-31 Janssen Biotech, Inc. Combination therapies with anti-CD38 antibodies
US12286474B2 (en) 2014-12-04 2025-04-29 Janssen Biotech, Inc. Anti-CD38 antibodies for treatment of acute myeloid leukemia
US10793630B2 (en) 2014-12-04 2020-10-06 Janssen Biotech, Inc. Anti-CD38 antibodies for treatment of acute myeloid leukemia
US10766965B2 (en) 2015-05-20 2020-09-08 Janssen Biotech, Inc. Anti-CD38 antibodies for treatment of light chain amyloidosis and other CD38-positive hematological malignancies
US12091466B2 (en) 2015-05-20 2024-09-17 Janssen Biotech, Inc. Anti-CD38 antibodies for treatment of light chain amyloidosis and other CD38-positive hematological malignancies
US10668149B2 (en) 2015-06-22 2020-06-02 Janssen Biotech, Inc. Combination therapies for heme malignancies with anti-CD38 antibodies and survivin inhibitors
US11021543B2 (en) 2015-06-24 2021-06-01 Janssen Biotech, Inc. Immune modulation and treatment of solid tumors with antibodies that specifically bind CD38
US11566079B2 (en) 2015-11-03 2023-01-31 Janssen Biotech, Inc. Subcutaneous formulations of anti-CD38 antibodies and their uses
US11708419B2 (en) 2015-11-03 2023-07-25 Janssen Biotech, Inc. Subcutaneous formulations of anti-CD38 antibodies and their uses
US11708420B2 (en) 2015-11-03 2023-07-25 Janssen Biotech, Inc. Subcutaneous formulations of anti-CD38 antibodies and their uses
US10781261B2 (en) 2015-11-03 2020-09-22 Janssen Biotech, Inc. Subcutaneous formulations of anti-CD38 antibodies and their uses
US11732051B2 (en) 2015-11-03 2023-08-22 Janssen Biotech, Inc. Subcutaneous formulations of anti-CD38 antibodies and their uses
US10385135B2 (en) 2015-11-03 2019-08-20 Janssen Biotech, Inc. Subcutaneous formulations of anti-CD38 antibodies and their uses
US11618787B2 (en) 2017-10-31 2023-04-04 Janssen Biotech, Inc. Methods of treating high risk multiple myeloma

Also Published As

Publication number Publication date
JP4233608B2 (ja) 2009-03-04

Similar Documents

Publication Publication Date Title
US6777388B1 (en) Leptin-related peptides
KR101201339B1 (ko) 인간 ｅｐｏ 미메틱 힌지 코어 미메티바디, 조성물, 방법및 용도
WO1998016245A1 (fr) Procede de determination d'un auto-anticorps
JP4859248B2 (ja) 可溶性Ｇタンパク質共役型レセプター（ｓＧＰＣＲ）に関する組成物および方法
US20050191301A1 (en) Mammalian EPO mimetic CH1 deleted mimetibodies, compositions, methods and uses
JP2002533058A (ja) ９７個のヒト分泌タンパク質
TWI227734B (en) A novel polypeptide hormone phosphatonin
UA129672C2 (uk) Антитіло до trem-1 та його застосування
JP2002512521A (ja) ３２個のヒト分泌タンパク質
JP2002508652A (ja) 新規なヒト増殖因子
JPWO1998016245A1 (ja) 自己抗体測定方法
JP2002537796A (ja) ヒトグリコシル化酵素
CN113637070A (zh) 抗spike蛋白的抗体或抗原结合片段及其应用
JP2006325596A (ja) シアロアドヘシンファミリーメンバー−２（ｓａｆ−２）
JP2002514925A (ja) １９個のヒト分泌タンパク質
BRPI0717155A2 (pt) Agonistas do receptor de epo humana, composições, métodos e usos para prevenção ou tratamento das condições relacionadas á intolerância á glicose
US20030166561A1 (en) Peptide
JP2002300891A (ja) 新規化合物
JP2008509655A (ja) Ｕｎｃ５ｈ２のスプライス変異体
JPH1156378A (ja) 変異型ヒト成長ホルモンとその用途
US20030050434A1 (en) Peptide
ES2201547T3 (es) Icam-4 y usos diagnosticos de las mismas.
CN113637083A (zh) 用于治疗冠状病毒的融合蛋白及其应用
JP2001502359A (ja) シアロアドヘシンファミリー４（ＳＡＦ−４）ｃＤＮＡ
LT4877B (lt) Prv-1 genas ir jo panaudojimas

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): JP US

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)