Method of treating alzheimer's disease

FIELD: medicine.

SUBSTANCE: group of inventions refers to medicine and concerns using a peptide conjugated with a protein representing a keyhole limpet hemocyanin (KLH) protein used as an immunogen for preparing antibodies specifically recognising any of prevailing versions of beta-amyloid peptide Aβ40 and Aβ42; or using an antibody, or an active fragment, or an antibody derivative of the above peptide in preparing a therapeutic agent for preventing and/or treating a disease characterised by amyloid accumulation in the patient's brain.

EFFECT: group of inventions provides effective immunisation, reduces an amyloid load and a quantity of brain amyloid plaques.

5 cl, 3 ex

 

The technical field to which the invention relates

The present invention relates to a method of treatment and/or prevention of diseases associated with amyloid deposits, which include Alzheimer's disease.

The level of technology

Certain facts are known about the biochemical and metabolic phenomena associated with the presence of Alzheimer's disease (AD). Two structural and histopathological changes observed in the brain of cases of AD are neurofibrillary beams (NFT) and amyloid deposits. Vnutrineironalnah neurofibrillary beams are also present in other neurodegenerative diseases, but the presence of amyloid deposits in vnutrineironalnah space (naranya plaques)and in close proximity to the microvessels (vascular plaques), as it seems, is a characteristic feature of AD. Of them naranya plaques seem to be the most common (Price, D.L. and co-workers, Drug Development Research (1985) 5:59-68).

The main data component of amyloid plaques is a peptide of 40-42 amino acids, called amyloid peptide Aβ4.

Amyloid peptide Aβ4 is a polypeptide, which is formed as a result of proteolysis of membrane glycoproteins, denoted proteins-amyloid precursor peptide Aβ4 (βAPP). Data protein precursor amyloid peptide is IDA, consist of from 695 to 770 amino acids, all of which are encoded by the same gene.

Identified two main options amyloid peptide Aβ4 - peptide Aβ40 and Aβ42, containing 40 and 42 amino acids, respectively, which have different tissue distribution both in physiological and in pathological conditions. Variant of 42 amino acids is the predominant form in amyloid plaques, localized in the brain of patients with AD.

Up to the present time offered a variety of possible solutions to ensure a possible vaccine against AD.

In the European patent EP526511 proposed introduction of homeopathic doses of Aβ in patients with pre-installed AD. However, because of the applied dose levels of circulating endogenous Aβ in plasma vary considerably and, thus, the benefits of such therapy are expected.

Schenk et al. (Nature 1999; 400: 173-177) describe the Aβ42 immunization of transgenic PDAPP mice, which hyperexpression mutant APP person, preventing thereby the formation of amyloid plaques, the degeneration of neurites and astroglia.

In the application WO9927944 (Schenk D.) described the treatment of AD by the introduction of patient Aβ42.

Phase III clinical trials in 360 patients with a diagnosis of moderate and moderate AD in 4 European countries and in the United States, in which amyloid peptide Aβ42 was used in the image quality is as antigen, was stopped after reports of encephalitis in some patients (Scrip Daily Online, 25 Feb 2002, S007455320, The Scientist 16[7]: 22, April 1, 2002).

Among some of the possible problems that, when used as a vaccine endogenous protein (or a protein naturally present in the animal, which Vaccinium), as in the case of peptide Aβ42, when the body responds by making antibodies against Aβ42 and against smaller fractions, which may have also not yet known physiological functions, you can mention the problem of the possible development of autoimmune diseases caused by the production of antibodies against the endogenous protein, the difficulty in the development of the immune response due to the inability of the immune system to recognize endogenous antigens and the possible development of acute inflammatory response.

The present invention is the treatment of Alzheimer's disease and other amyloid diseases by administration of a peptide, C-terminal part of the Aβ conjugated with protein, where in the preferred implementation of the present invention, this protein represents hemocyanin mollusk fissurella.

Disclosure of invention

The present invention relates to a vaccine for the prevention and/or treatment of Alzheimer's disease and other related amyloid diseases.

In accordance with preferred the implementation of the present invention features a vaccine for the prevention and/or treatment of Alzheimer's disease and other related diseases, which overcomes the drawbacks associated with peptides, proteins or endogenous immunogenum.

Examples of other diseases characterized by amyloid deposits are Icelandic inherited syndrome, multiple myeloma and spongiform encephalitis, including disease of Creutzfeldt-Jakob disease.

Induction of an immune response can be active, for example, when an immunogen is administered to the production of antibodies that interact with Aβ in a patient, or passive, for example, when injected antibody, which itself interacts with Aβ in a patient.

For the objectives of the present invention, the following terms are defined as follows.

The term "related amyloid disease" includes diseases associated with accumulation of amyloid, which can be limited to one body - the local amyloidosis, or distributed in several organs systemic amyloidosis. Secondary amyloidosis may be associated with chronic infections (such as tuberculosis), familial Mediterranean fever (FMF) and other types of systemic amyloidosis found in patients with prolonged treatment with hemodialysis. Local forms of amyloidosis include, but are not limited to the above, type II diabetes and any other related to this disease, neurodegenerative disease spongiform encephalitis, cor is Vij spongiform encephalitis, the disease of Creutzfeldt-Jakob disease, Alzheimer's disease, cerebral amyloid angiopathy.

The term "passive immunization" is used in relation to the introduction of antibodies or their fragments to the individual to create immunity in the individual.

In the first aspect of the invention includes the use of a peptide that acts or as an immunogen or as antibodies, in the preparation of medicines for the prevention and/or treatment of diseases characterized by accumulation of amyloid deposits. These methods consist in the induction of an immune response against a peptide component of an amyloid deposits in a patient. This induction can be active with the introduction of the immunogen or passive with the introduction of the antibody or active fragment or derivative of the antibody.

In a preferred implementation of the present invention the disease is a disease of Alzheimer's.

Received medication may be used in asymptomatic patients and in patients exhibiting symptoms of the disease.

In accordance with the present invention, compositions capable of inducing an immune response directed against specific components of amyloid plaques, is effective in the treatment or prevention of diseases associated with amyloid deposits. In particular, according to the according to an aspect of the present invention, it is possible to prevent the progression or reduce the symptoms and/or reduce the deposition of amyloid in an individual when entering the patient immunostimulatory dose of peptide or antibody obtained against him.

In accordance with an aspect of the present invention, antibodies are produced by immunizing mammals or birds by using as immunogen peptide conjugated to a protein.

In accordance with a preferred implementation of the present invention, mammals, used for immunization may constitute ruminants, horses, lagomorphs, carnivores, primates, or any other animal, which you can get adequate amount of serum to separate her antibodies. Among birds, used for immunization, applicants may be noted, but not in terms of limitations, among other Galliformes, Anseriformes and Serves.

In accordance with a preferred implementation of the present invention proposed the use of a peptide conjugated to a protein, which acts as an immunogen for the production of antibodies that can specifically recognize any of the prevailing variants of beta-amyloid peptide Aβ40 or Aβ42 in preparation of medicines for the prevention and/or treatment of diseases characterized by the accumulation of amyl is innych deposits in the brain of the patient.

In accordance with the preferred implementation of the present invention, the protein used for conjugation with the peptide is a protein mollusk fissurella.

In accordance with the preferred implementation of the present invention, the peptide is selected from the group consisting of peptide SEQ ID No 1, peptide SEQ ID No 2, peptide SEQ ID No 3, peptide SEQ ID No 4, peptides resulting from shortening by removing amino acid residues from the N-end and/or C-terminal ends of the SEQ ID No 1, SEQ ID No 2, SEQ ID No 3 or SEQ ID No 4, and peptides obtained by lengthening by adding the residue to any of the peptides of SEQ ID No 1, SEQ ID No 2, SEQ ID No 3 or SEQ ID No 4.

In accordance with another preferred implementation, the peptide is selected from the group which includes the peptide SEQ ID No 1, a peptide with the sequence obtained by deletion of residues N-terminal and/or C-terminal amino acids of SEQ ID No 1, and the peptides obtained by adding to any of the preceding sequences of amino acid residues required for conjugation with protein.

In another preferred implementation of the present invention the peptide is selected from the group consisting of peptide SEQ ID No 2, peptides with the sequence obtained by deletion of residues N-terminal and/or C-terminal amino acids of SEQ ID No 2, and peptides, obtained is the result of adding to any of the preceding sequences amino acid residues, required for conjugation with protein.

In another preferred implementation of the present invention the peptide is selected from the group consisting of peptide SEQ ID No 3, peptides with the sequence obtained by deletion of residues N-terminal and/or C-terminal amino acids of SEQ ID No 3, and peptides obtained by adding to any of the preceding sequences of amino acid residues required for conjugation with protein.

In another preferred implementation of the present invention the peptide is selected from the group consisting of peptide SEQ ID No 4, peptides with the sequence obtained by deletion of residues N-terminal and/or C-terminal amino acids of SEQ ID No 4, and peptides obtained by adding to any of the preceding sequences of amino acid residues required for conjugation with protein.

In accordance with another implementation of the present invention, the application of the antibody or active fragment or derivative of the antibody, which specifically recognizes any of the prevailing variants of beta-amyloid peptide Aβ40 or Aβ42 in preparation of medicines for the prevention and/or treatment of diseases characterized by the accumulation of amyloid deposits in the brain of the patient.

In accordance with a preferred what sushestvennee of the present invention, the antibody or active fragment or derivative of the antibody, which specifically recognizes any of the prevailing variants of Aβ peptide, get against a peptide selected from the group consisting of SEQ ID No 1, SEQ ID No 2, SEQ ID No 3, SEQ ID No 4, optional shortened by deleting amino acid residues from the N-end and/or C-all, and need not be elongated by adding amino acid residues that are suitable for conjugation with protein.

In another preferred implementation, the specified antibody, or active fragment or derivative of the antibody obtained by immunization of mammals or birds peptides selected from the group that includes the peptide SEQ ID No 1, a peptide with the sequence obtained by deleting N-terminal and C-terminal amino acid residues of SEQ ID No 1, and the peptides obtained by adding to any of the preceding sequences of amino acid residues required for conjugation with protein.

In another preferred implementation, the specified antibody, or active fragment or derivative of the antibody obtained by immunization of mammals or birds peptides selected from the group that includes the peptide SEQ ID No 2, peptides with the sequence obtained by deleting N-terminal and C-terminal amino acid residues of SEQ ID No 2, the peptides, obtained by adding to any of the preceding sequences of amino acid residues required for conjugation with protein.

In another preferred implementation, the specified antibody, or active fragment or derivative of the antibody obtained by immunization of mammals or birds peptides selected from the group that includes the peptide SEQ ID No 3, peptides with the sequence obtained by deleting N-terminal and C-terminal amino acid residues of SEQ ID No 3, and the peptides obtained by adding to any of the preceding sequences of amino acid residues required for conjugation with protein.

In another preferred implementation, the specified antibody, or active fragment or derivative of the antibody obtained by immunization of mammals or birds peptides selected from the group that includes the peptide SEQ ID No 4, peptides with the sequence obtained by deleting N-terminal and C-terminal amino acid residues of SEQ ID No 4, and the peptides obtained by adding to any of the preceding sequences of amino acid residues required for conjugation with protein.

In this specification, amino acids reduce using single-letter codes used in this field, as follows:

A = Ala= alanine

C = Cys = cysteine

D = Asp = aspartic acid

E = Glu = glutamic acid

F = Phe = phenylalanine

G = Gly = glycine

H = His = histidine

I = Ile = isoleucine

K = Lys = lysine

L = Leu = leucine

M = Met = methionine

N = Asn = asparagine

P = Pro = Proline

Q = Gln = glutamine

R = Arg = arginine

S = Ser = serine

T = Thr = threonine

V = Val = valine

W = Trp = tryptophan

Y = Tyr = tyrosine

The sequence described earlier in this invention and identified as SEQ ID No 1, SEQ ID No 2, SEQ ID No 3, SEQ ID No 4 correspond to the following amino acid sequences:

SEQ ID NO 1 LVFFAEDV

SEQ ID NO 2 GLMVGGVV

SEQ ID NO 3 GLMVGGVVIA

SEQ ID NO 4 RHDSGYEVHHQK

The antibodies raised against these peptides are given codes SAR-1, SAR-2, SAR-3 and e-4 in accordance with what is specified below:

SEQ ID NO 1 SAR-2

SEQ ID NO 2 SAR-3

SEQ ID NO 3 SAR-4

SEQ ID NO 4 SAR-1

Information related to the identification of peptide sequences described in the present invention, which is appended to this document in a format for computer reading, is a list of sequences that are present in this document.

The present invention is illustrated by the following examples.

Example 1. Obtaining polyclonal antibodies.

By immunization of new Zealand white rabbits received four polyclonal antitherapeutic four peptides conjugated to KLH, which were used as immunogen.

Each immunogen was injected with two rabbits, five injections each rabbit: the first intradermal injection of the conjugate peptide-KLH in SFR, emulsified in complete Freund's adjuvant, and four additional intramuscular injection as a maintenance dose at 14, 28, 49 and 80 days of the same conjugate the peptide-KLH in SFR, but this time emulsified in incomplete Freund's adjuvant, the selection of blood for 90 days to determine the presence of antibodies.

After collection, the blood was separated serum and produced a preliminary purification by desalting, and then the antibody was purified by affinity for the matrix, containing 1.5 ml of activated substances EMD-Epoxy (Merck), to which was added 5 mg of the corresponding peptide. Purified fractions were preserved in 0.1% BSA (Sigma) and kept at 4°C, and as a cryoprotectant you can add 20-50% glycerol.

Example 2. The Western blot turns to β.

1. The electrophoresis.

Used way Lemli described in Current Protocols in Molecular Biology, John Wiley and Sons, New York, 1998, modified to improve the separation of small peptides.

Used the device Miniprotean 3 from Bio-Rad.

Used 15%acrylamide gel, mixed with the following components:

Separating gel (15%)
The original solutionsConcentrating gel, ál
40% acrylamide3,75 ml500
Tris 3 M, pH 8,453,3 ml250
Glycerin1,05 ml-
Water1.9 ml4,2
DDS-Na 20%50 µl18,6
APS 10%50 µl25
TEMED10 ál5

Used the original solutions of peptides Aβ40 and 42 with a concentration of 1 mg/ml (dissolved in SFR). Selected the necessary amount of data solutions for each of the samples and brought up to 20 μl with SBLT (SBL + Tris base 2 M). The samples were then boiled for 5 minutes for denaturation of peptides and the possible removal of proteases.

The middle of the cell was filled with cathode buffer and the environment - anode buffer, and the composition of these buffers was as follows:

The anode buffer.

24.2 g Tris base (final concentration 0.2 M)dilute to 1 l H2O,

is avesti pH to 8.9 with concentrated HCl,

store at 4°C for up to 1 month.

The cathode buffer.

12,11 g Tris base (final concentration 0.1 M),

17,92 g Tricine (final concentration 0.1 M,)

1 g DDS-Na (final concentration of 0.1%)

dilute to 1 l H2O,

not to bring the pH.

Store at 4°C for up to 1 month.

Finally, the samples were introduced into the wells: 20 µl/well. Using Standard Polypeptide Kaleidoscope from Bio-Rad as a marker movement was started at low voltage (30 V), and then after about 1 hour of electrophoresis voltage was increased to 100 C.

2. Transfer to the membrane.

Separated proteins in the gel were transferred to PVDF membrane using electroblotting. In the booklets for transfer were placed the following:

Back - sponge - 3 sheets of Whatman paper (or filter paper - gel - membrane - 3 sheets of Whatman paper - sponge - side imprint.

After that, the cell was filled with buffer electroblotting:

Glycine 38 nm

Tris base 50 mm

Methanol 40%

The transfer was made within 2 hours at 200 mA. During the transfer buffer was stirred with a magnetic stirrer.

3. Incubation with antibodies.

Antibodies and milk powder was dissolved in SFR-t (SFR + 0.5% tween-20), leaching was also produced using SFR-T.

After transfer, the surface of the membrane was blocked with 5%milk powder solution in t the value of 1 hour with stirring at room temperature (RT).

After that, the membrane was washed 2×5 minutes at RT.

Then it was incubated with the primary antibody (SAR-1, SAR-2, SAR-3 or e-4) for 1 hour at RT in a dilution of at least 1:500 in SFR-T.

The membrane was washed 3×10 minutes at RT. Then it was incubated with the secondary antibody: goat-HRP against rabbit for 1 hour at RT (1:10000 in all cases).

Again repeated wash the membrane 3×10 minutes at RT.

4. Color.

After the last washing, the membrane was incubated with a solution chemoluminescence set using ECL kit+Plus from Pharmacia.

The membrane was wrapped in cellophane and exposed to film with a double emulsion (Hyperfilm MP from Amersham) for various periods of time from 30 seconds to 2 minutes.

Example 3. Immunohistochemistry with antibodies SAR-1, SAR-2, SAR-3 and SAR-4 tissue of the human brain.

The tissue slices were fixed in paraffin according to the following stages:

a) fixation in neutral 10%formaldehyde,

b) dehydration through successive stages with increasing concentrations of alcohol,

c) wiring through xylene and paraffin, and the last stage is carried out in a furnace at 60-62°C,

d) obtaining paraffin blocks of sections of 4 μm, which was mounted on the glass.

The slices were then deparaffinization wiring through the following solutions:

Xylene 100% 10 minutes

Xylene 100% 10 mine is

Ethanol 100% for 5 minutes

Ethanol 100% for 5 minutes

Ethanol 96% 5 minutes

Ethanol 90% in 5 minutes

Ethanol 70% 5 minutes

SFR 5 minutes x 3 times

Then they were processed as follows:

a) 96%formic acid for 3 minutes in a fume hood under stirring,

b) a quick water rinse,

c) washing SFR 2×5 minutes

d) blocking of endogenous peroxidase for 15 minutes in a solution composed of 70 ml SFR, 30 ml of methanol and 1 ml of H2O2,

e) washing SFR 3×5 minutes

f) washing SFR/T (0,5% Triton or tween-20 in SFR) 3×5 minutes

(g) blocking of nonspecific binding with goat serum (normal goat serum)diluted 10:100 in SFR/T, within 2 hours,

h) incubation with the primary antibodies overnight at 4°C in a humid chamber:

Sar-1... a Dilution of 1:150 in SFR

Sar-2... a Dilution of 1:1500 in SFR

Sar-3... a Dilution of 1:1500 in SFR

Sar-4... a Dilution of 1:2000 in SFR

i) washing SFR/T 3×5 minutes

j) by incubation with secondary antibody (goat against rabbit)diluted 1:200 SFR, within 45 minutes

(k) washing SFR 4×5 minutes

l) incubation ABC (avidin-bioteknologi complex) Vector Labs in a dilution of 1:100 in SFR/T for 45 minutes in the dark when saving data conditions to completion of the development of painting,

m) washing SFR 3×5 minutes

n) the expression in diaminobenzidine (DAB).

Time controlled e is pricheski under stereoscopic microscope. For this, first of all, I made a wash in 0.5 M solution of Tris-HCl for 10 minutes under stirring, followed by incubation with diaminobenzidine substrate (DAB)dissolved in 0.05 M Tris-HCl, and which was added to 0.5 μl/ml of H2O2at 4°C. After the reaction was conducted three leaching in SFR at 4°C for 5 minutes each, and then produced dehydration in ethanol at 70, 90 and 100% for 2 minutes each time, the wiring through xylene for 4 minutes and then wiring through xylene for 2 minutes, after which the sections were mounted with Eukitt for examination under a microscope.

Sequence listing

Number of sequences: 4

Information about the sequence 1:

Sequence properties:

Length: 8

Type: amino acid

The molecule type: peptide

Source: Chemical synthesis

Description sequence:

SEQ ID NO 1

LeuValPhePheAlaGluAspVal
15

The sequence information 2:

Sequence properties:

Length: 8

Type: amino acid

The molecule type: peptide

Source: Chemical synthesis

Description sequence:

SEQ ID NO 1

GlyLeuMetValGlyGlyValVal
15

The sequence information 3:

Sequence properties:

Length: 10

Type: amino acid

The molecule type: peptide

Source: Chemical synthesis

Description sequence:

SEQ ID NO 1

GlyLeuMetValGlyGlyValVal IleAla
1510

The sequence information 4:

Sequence properties:

Length: 12

Type: amino acid

The molecule type: peptide

Source: Chemical synthesis

Description sequence:

SEQ ID NO 4

ArgHisAspSerGlyTyrGluValHisHisGlnLys
1510

1. Skin is of the peptide, conjugated with protein, representing a protein mollusk fissurella (KLH), which acts as an immunogen to generate antibodies that can specifically recognize any of the prevailing variants of beta-amyloid peptides Aβ40 and Aβ42 in preparation of medicines for the prevention and/or treatment of diseases characterized by the accumulation of amyloid deposits in the brain of a patient, where the peptide consists of SEQ ID No 3.

2. The use according to claim 1, wherein the disease is a disease of Alzheimer's.

3. The use of antibodies, or active fragment or derivative of the antibody, which specifically recognizes any of the prevailing variants of beta-amyloid peptides Aβ40 and Aβ42 in preparation of medicines for the prevention and/or treatment of diseases characterized by the accumulation of amyloid deposits in the brain of a patient, where the antibody or active fragment or derivative of the antibody, which specifically recognizes any of the prevailing variants of Aβ peptide derived from the peptide consisting of SEQ ID No 3.

4. The use according to claim 3, wherein the disease is a disease of Alzheimer's.

5. The use according to claim 3, characterized in that said antibody or active fragment or derivative of the antibody obtained by immunizing mammals of elliptic peptide SEQ ID No 3.



 

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FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed group of inventions relates to medicine, namely to cardiology, and deals with treatment and prevention of arterial hypertension. For this purpose pharmaceutical composition, containing activated potentiated antibodies to angiotensin II receptor and to endothelial NO-synthase, is introduced.

EFFECT: method ensures effective treatment of arterial hypertension due to synergic antihypertensive action of composition components.

11 cl, 2 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed group relates to medicine, namely to cardiology, and deals with treatment of chronic heart failure. For this purpose pharmaceutical composition, containing activated potentiated forms of antibodies to angiotensin II receptor and to endothelial NO-synthase is introduced.

EFFECT: synergic action of pharmacological composition components ensures improvement of systolic function of left ventricle and increase of tolerance to physical load in said group of patients.

11 cl, 2 ex, 2 tbl

Antibody to epha2 // 2525133

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to field of immunology, medicine and biotechnology. Claimed are versions of anti-EPHA2 antibodies. Claimed antibodies are bound with polypeptide, consisting of amino acids 426-534 in SEQ ID NO:8. Also described are hybridomes, which produce such antibodies, and pharmaceutical compositions and methods of application of said antibodies and compositions.

EFFECT: invention can be used in medicine.

74 cl, 14 dwg, 14 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to the field of immunology. Disclosed is a method of treating rheumatoid arthritis, chronic arthritis in children or Castelman's disease, application of an antibody in the said method, as well as application of an antibody in production of a medication for treatment of rheumatoid arthritis, chronic arthritis in children or Castelman's disease. The antibody by the claimed invention possesses an improved antigen-neutralising ability, pharmacokinetics, immunogenicity, safety and physicochemical properties and can be further applied in therapy of diseases, associated with the activation of the receptor IL-6.

EFFECT: claimed is the medication for treatment of rheumatoid arthritis, chronic arthritis in children or Castelman's disease, representing the antibody against the receptor IL-6, obtained on the basis of the antibody TOCILIZUMAB.

12 cl, 5 dwg, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to the field of biotechnology and immunology. Described are versions of antibodies, binding the GRM molecule, as well as their antigen-binding fragments, amino acid sequences of variable parts of which are presented in the claim materials. Nucleic acid, coding the said antibodies, is presented. Claimed is a method of obtaining the RGM-binding protein, which includes cultivation of a host cell in a culture medium under conditions suitable for obtaining the binding protein, capable of binding with RGM, where the host cell contains an expression vector, containing the separated nucleic acid, coding the said antibody. Described is a pharmaceutical composition for treating a disease, in which the SGM A activity produces a negative impact, which contains a therapeutically efficient quantity of the said antibody and a pharmaceutically acceptable carrier. Claimed is an application of the said antibody for obtaining a medication, used for a) reduction of hRGM A binding with a patient's Neogenin receptor; or b) for reduction of hRGM A binding with BMP-2 and BMP-4 in the patient.

EFFECT: invention makes it possible to obtain antibodies against GRM, which are used for treating diseases, associated with excessive interaction of RGM with the Neogenin receptor, BMP-2 and BMP-4.

13 cl, 16 dwg, 10 tbl, 11 ex

FIELD: medicine.

SUBSTANCE: claimed invention relates to biotechnology and represents a polypeptide construction for treatment, prevention and relief of disorders, associated with an adhesion of platelets and platelet-mediated aggregation or its dysfunction, which includes one or more single-domain antibodies, aimed against the von Willebrand factor (vWF), and one or more single-domain antibodies aimed against serum albumen (SA). The invention also relates to nucleic acid, coding such polypeptide construction, to compositions, containing the said construction, and to its application for obtaining medications for prevention, treatment and relief of the said disorders.

EFFECT: claimed invention makes it possible to extend an assortment of medications for treatment, prevention and relief of disorders, associated with the platelet adhesion and platelet-associated aggregation or its dysfunction.

15 cl, 30 dwg, 32 tbl, 69 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a peptide represented by the formula (I) X1-Leu-X2-Leu-X3, where X1 is Glu or Asp, X2 is His, Lys or Arg, X3 is Asp or Glu, at that Glu, Asp, Leu, His, Lys and Arg, or its pharmaceutically acceptable salt and its compositions for treatment or prevention of cartilage damage and/or arthritis.

EFFECT: proposed peptide can affect the regeneration of cartilage tissue, inhibition of expression of the enzyme causing cartilage tissue matrix degradation, or inhibition of chondrosteosis.

7 cl, 2 tbl, 11 dwg, 15 ex

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