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WO2022217923A1 - Anticorps anti-igf-1r et son utilisation - Google Patents

Anticorps anti-igf-1r et son utilisation Download PDF

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Publication number
WO2022217923A1
WO2022217923A1 PCT/CN2021/132570 CN2021132570W WO2022217923A1 WO 2022217923 A1 WO2022217923 A1 WO 2022217923A1 CN 2021132570 W CN2021132570 W CN 2021132570W WO 2022217923 A1 WO2022217923 A1 WO 2022217923A1
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seq
antibody
amino acid
acid sequences
sequences shown
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郭树华
马琳
张鹏
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Suzhou Pro Heal Pharmaceuticals Technology Co Ltd
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Suzhou Pro Heal Pharmaceuticals Technology Co Ltd
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    • 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
    • C07K16/2869—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against hormone receptors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic 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
    • 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
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/51—Complete heavy chain or Fd fragment, i.e. VH + CH1
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/515—Complete light chain, i.e. VL + CL
    • 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
    • C07K2317/50—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
    • C07K2317/565—Complementarity determining region [CDR]
    • 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

Definitions

  • the invention relates to the technical field of biomedicine, in particular to an anti-IGF-1R antibody and an application thereof.
  • TAO Thyroid-associated ophthalmopathy
  • endocrine exophthalmos also known as endocrine exophthalmos, infiltrative exophthalmos, and thyroid ophthalmopathy
  • TAO is mostly bilateral, but asymmetric or unilateral disease can also occur.
  • TAO with hyperthyroidism accounts for about 90%, which can occur at the same time as hyperthyroidism, or before or after hyperthyroidism.
  • Some patients with hypothyroidism also have symptoms of TAO.
  • Thyroid-related ophthalmopathy can cause proptosis, eyelid contracture, extraocular muscle dysfunction, conjunctival hyperemia, periorbital edema, etc.
  • thyroid-related ophthalmopathy is a site-specific autoimmune disease dominated by cellular immunity, triggered by a common antigen expressed by thyroid epithelial cells, orbital preadipocytes and fibroblasts. Inflammation, increased orbital fibroblasts, and increased orbital adipocytes lead to proptosis, triggering symptoms of thyroid-related eye disease.
  • IGF-1R Insulin-like growth factor 1 receptor
  • SEQ ID NO: 1 belongs to the tyrosine protein kinase receptor family and is a cell surface transmembrane protein that can be mediated by IGF- 1 and IGF-2 (both insulin growth factors) are activated, and their overexpression may be associated with the pathogenesis of multiple sclerosis, Crohn's disease, pulmonary fibrosis and other malignant tumors and autoimmune diseases.
  • Anti-IGF-1R antibodies can be detected in most TAO patients, but rarely found in normal people.
  • IGF-1R-related IgG can activate IGF-1R-positive orbital fibroblasts derived from patients with thyroid-related eye disease, thereby activating Akt/FRAP/mTOR/P70s6k channels to induce interleukin-16 on orbital fibroblasts and regulate normal activation
  • Akt/FRAP/mTOR/P70s6k channels to induce interleukin-16 on orbital fibroblasts and regulate normal activation
  • RANTES normal T cell expressed and secreted factor
  • T cell chemokines causes the inflammatory infiltration of T lymphocytes and the production of hyaluronic acid, all of which are It indicated that IGF-1R may be involved in the development of TAO as a second antigen.
  • Anti-IGF-1R antibodies achieved the primary and all secondary endpoints in clinical trials for the treatment of thyroid eye disease, and could significantly improve the symptoms of proptosis.
  • there are currently no other antibodies against IGF-1R at home and abroad for the treatment of thyroid eye diseases such as patents CN200880011970.4, CN200880114015.3, CN200780011979.0, CN200980137713.3, US20190040141, US20090175868, US200600
  • the anti-IGF-1R antibodies are used for the treatment of malignant tumors. Therefore, in the field of thyroid-related eye diseases, it is very necessary to develop novel IGF-1R therapeutic antibodies for the treatment of this disease.
  • antibody refers to a glycoprotein comprising a heavy (H) and light (L) chain interconnected by disulfide bonds (S-S).
  • Each heavy chain consists of a heavy chain variable region (abbreviated herein as VH) and a heavy chain constant region.
  • the heavy chain constant region consists of three domains, CH1, CH2 and CH3.
  • Each light chain consists of a light chain variable region (abbreviated herein as VL) and a light chain constant region.
  • the light chain constant region consists of one domain, CL.
  • Light chains are divided into two categories: kappa-type light chains and lambda-type light chains.
  • VH and VL regions can be further subdivided into hypervariable regions (complementarity determining regions (CDRs), with more conserved regions (framework regions (FR)) interposed therebetween.
  • CDRs complementarity determining regions
  • FR frame regions
  • Each VH and VL consists of three CDRs and four
  • the FR composition is arranged in the following order from amino terminus to carboxy terminus: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4.
  • Fc domain or “Fc region” are used herein to define the C-terminal region of an immunoglobulin heavy chain that contains at least a portion of the constant region.
  • the term includes native sequence Fc regions and variant Fc regions.
  • a native immunoglobulin "Fc domain” contains two or three constant domains, a CH2 domain, a CH3 domain and an optional CH4 domain.
  • an immunoglobulin Fc domain comprises the second and third constant domains (CH2 and CH3 domains) derived from the two heavy chains of antibodies of the IgG, IgA and IgD classes; or The second, third and fourth constant domains (CH2 domain, CH3 domain and CH4 domain) of both heavy chains of IgM and IgE class antibodies.
  • the sequence of Fc is derived from the sequence structure existing in nature or the Fc sequence through genetic engineering, such as antibody-dependent cell-mediated cytotoxicity (antibody-dependent cell-mediated cytotoxicity, ADCC) and/or complement-dependent cytotoxicity "LALA” mutation, "PGLALA” mutation, "N297A” mutation, etc. with reduced effect (complement dependent cytotoxicity, CDC) (amino acid sequence numbering is defined according to the rules of Kabat et al. for antibody amino acid sequence coding, (Kabat et al., Sequences of Proteins of Immunological Interest, 4th edition, U.S. Department of Health and Human Services, National Institutes of Health (1987)).
  • CDR refers to regions of an antibody variable domain that are hypervariable in sequence and form structurally defined loops ("hypervariable loops") and/or contain antigen-contacting residues ("antigen contact points") .
  • the CDRs are mainly responsible for binding to antigenic epitopes.
  • the CDRs located within the variable domains of antibody heavy chains are referred to as HCDR1, HCDR2 and HCDR3, while the CDRs located within the variable domains of antibody light chains are referred to as LCDR1, LCDR2 and LCDR3.
  • the CDR assignment of the present invention is based on the Kabat amino acid sequence numbering system and the CDR definition system (Kabat et al., Sequences of Proteins of Immunological Interest, 4th edition, U.S. Department of Health and Human Services, National Institutes of Health (1987)).
  • expression vector refers to a vector containing recombinant polynucleotides, which is a vector that adds expression elements (such as promoter, RBS, terminator, etc.) to the basic skeleton of the cloning vector, so that the target gene can be expressed.
  • the expression vector contains sufficient cis-acting elements for expression; other elements for expression can be provided by the host cell or in an in vitro expression system.
  • Expression vectors include all those known in the art, including cosmids, plasmids (eg, naked or contained in liposomes) and viruses (eg, lentiviruses, retroviruses, adenoviruses) that are incorporated into recombinant polynucleotides virus and adeno-associated virus).
  • cosmids eg, naked or contained in liposomes
  • viruses eg, lentiviruses, retroviruses, adenoviruses
  • any concentration range, percentage range, ratio range or integer range should be understood to include any integer value within the stated range and, where appropriate, fractions thereof (such as tenths and percents of integers) one), unless otherwise specified.
  • the present invention provides an antibody that binds to IGF-1R and its application in the preparation of medicines.
  • the antibody and related medicines can be used for the prevention or treatment of thyroid-related eye diseases.
  • the present invention provides an antibody that binds to IGF-1R.
  • the antibody consists of light and heavy chains.
  • the light chain complementarity determining region LCDR1 of the antibody is selected from SEQ ID NO:22, SEQ ID NO:25, SEQ ID NO:28, SEQ ID NO:31, SEQ ID NO:34, SEQ ID NO:37, SEQ ID NO:37,
  • LCDR2 is selected from SEQ ID NO:23, SEQ ID NO:26, SEQ ID NO:29, SEQ ID NO:32, SEQ ID NO :35, SEQ ID NO:38, SEQ ID NO:41, a kind of amino acid sequence shown in SEQ ID NO:44
  • LCDR3 is selected from SEQ ID NO:24, SEQ ID NO:27, SEQ ID NO:30 , SEQ ID NO: 33, SEQ ID NO: 36, SEQ ID NO: 39, SEQ ID NO: 42, one of the amino acid sequences shown in SEQ ID NO: 45;
  • the heavy chain complementarity determining region of the antibody HCDR1 is selected from the group consisting
  • the light chain variable region of the antibody is selected from SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID One of the amino acid sequences shown in NO:14 and SEQ ID NO:16
  • the heavy chain variable region of the antibody is selected from SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:7, One of the amino acid sequences shown in ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, and SEQ ID NO: 17.
  • the light chain and heavy chain variable regions of the antibody are selected from the group consisting of SEQ ID NO:2 and SEQ ID NO:3, SEQ ID NO:4 and SEQ ID NO:5, SEQ ID NO:6 and SEQ ID NO:7 , SEQ ID NO:8 and SEQ ID NO:9, SEQ ID NO:10 and SEQ ID NO:11, SEQ ID NO:12 and SEQ ID NO:13, SEQ ID NO:14 and SEQ ID NO:15, SEQ ID NO:12 and SEQ ID NO:13 One of the combinations of ID NO: 16 and SEQ ID NO: 17.
  • amino acid sequence of the light chain constant region of the antibody is shown in SEQ ID NO: 19.
  • the light chain of the antibody is formed by splicing the light chain variable region and the light chain constant region shown in SEQ ID NO: 19.
  • the amino acid sequence of the heavy chain constant region of the antibody is shown in SEQ ID NO: 18.
  • the heavy chain of the antibody is formed by splicing the variable region of the heavy chain and the constant region of the heavy chain shown in SEQ ID NO: 18.
  • the light chain and heavy chain of the antibody are the amino acid sequences shown in SEQ ID NO:70 and SEQ ID NO:71;
  • amino acid sequences shown in SEQ ID NO:84 and SEQ ID NO:85 are shown in SEQ ID NO:84 and SEQ ID NO:85.
  • the light chain and heavy chain form a complete anti-IGF-1R antibody through interchain disulfide bonds.
  • the present invention provides a biological molecule, vector or host cell, wherein the biological molecule, vector or host cell comprises a nucleic acid molecule encoding the antibody obtained by any of the above technical solutions.
  • the present invention provides the use of the above-mentioned IGF-1R-binding antibody and/or biological molecule, vector or host cell in the preparation of a medicament for the treatment or adjuvant treatment of autoimmune diseases.
  • the application includes, but is not limited to, the use of the above-mentioned antibody that binds to IGF-1R, the nucleotide sequence encoding the antibody and mutants thereof, the expression vector containing the above-mentioned nucleotide sequence, and the host cell containing the above-mentioned vector in the preparation of therapeutic or therapeutic drugs.
  • the antibody is separated and purified.
  • Said nucleotide sequences, expression vectors and host cells achieve said applications by expressing antibodies.
  • the antibody, nucleotide sequence and expression vector can be directly added to the medicine to realize the application.
  • the autoimmune diseases include but are not limited to diseases caused by abnormal thyroid function.
  • the disease caused by the abnormal thyroid function is thyroid-related eye disease.
  • thyroid-related ophthalmopathy includes but is not limited to: proptosis, eyelid retraction, delayed upper eyelid fall, extraocular muscle hypertrophy, conjunctival hyperemia, periorbital tissue edema, eyelid insufficiency, photophobia, lacrimation, foreign body sensation. , vision loss or diplopia.
  • the present invention provides a method for preparing the above-mentioned antibody that binds to IGF-1R.
  • the preparation method is to construct an expression vector to transfect a host cell with a nucleotide sequence encoding the antibody provided by any of the above technical solutions, and obtain an antibody that binds to IGF-1R through the expression of the host cell.
  • the present invention provides a pharmaceutical composition.
  • the pharmaceutical composition comprises the above-mentioned IGF-1R-binding antibody and/or biological molecule, vector or host cell.
  • the pharmaceutical composition also includes a pharmaceutically acceptable carrier and/or adjuvant.
  • the pharmaceutically acceptable carriers and/or auxiliary materials include but are not limited to: solubilizers, stabilizers and excipients.
  • the administration modes of the pharmaceutical composition include but are not limited to: subcutaneous injection, intradermal injection, intramuscular injection, intravenous injection, intravenous drip, and eyelid injection.
  • the pharmaceutical composition can be applied to the prevention and/or treatment of thyroid-related eye diseases, including but not limited to proptosis, eyelid retraction, upper eyelid retardation, extraocular muscle hypertrophy, conjunctival hyperemia, periorbital Tissue edema, eyelid insufficiency, photophobia, lacrimation, foreign body sensation, decreased vision, or diplopia.
  • thyroid-related eye diseases including but not limited to proptosis, eyelid retraction, upper eyelid retardation, extraocular muscle hypertrophy, conjunctival hyperemia, periorbital Tissue edema, eyelid insufficiency, photophobia, lacrimation, foreign body sensation, decreased vision, or diplopia.
  • the antibody binding to IGF-1R provided by the invention can effectively inhibit the proliferation of MCF7 cells, and can reduce the degree of extraocular myopathy of thyroid ophthalmopathy in rats, and provides a new way for developing new drugs for treating thyroid-related ophthalmopathy.
  • Figure 1 shows the results of the inhibition of the proliferation of MCF7 cells by the PHP1003-1 antibody.
  • Figure 2 shows the observation results of extraocular muscle tissue staining under a light microscope (400 ⁇ ) after 4 weeks of administration of the test product PHP1003-1 and the reference product in a rat model of hyperthyroidism and thyroid-related ophthalmopathy.
  • Recombinant human IGF-1R Human IGF-1R, Beijing Biopsis Biotechnology Co., Ltd., Cat. No. IGR-H5229
  • 2% BSA Beijing Soleibo Technology Co., Ltd., product number A8020
  • the obtained phage library was incubated with human IGF-1R, eluted, amplified and enriched with phages that bind to human IGF-1R. After repeating 3-4 times, the finally obtained phages were selected and amplified for clones. Clones with positive binding to human IGF-1R were obtained according to the detection method of phage ELISA. Molecules with complete variable region sequences as shown in Table 1 below were obtained after sequencing the positive clones.
  • the light chain variable region and light chain constant region (SEQ ID NO: 19) cloned in Example 1 were directly spliced to form a light chain
  • the heavy chain variable region and heavy chain constant region (SEQ ID NO: 19) cloned in Example 1 were directly spliced to form a light chain.
  • NO:18) direct splicing to form a heavy chain, specifically, as shown in Table 2 below, the light chain and heavy chain of the antibody are the amino acid sequences shown in SEQ ID NO:70 and SEQ ID NO:71;
  • amino acid sequences shown in SEQ ID NO:84 and SEQ ID NO:85 are shown in SEQ ID NO:84 and SEQ ID NO:85.
  • the genes were codon-optimized according to human host cells and routinely synthesized, and the genes were cloned into the vector pTT5 (ampicillin resistance) through 5'EcoRI and 3'HindIII.
  • the clones were selected for sequencing, and the correctly sequenced bacterial cells were selected for seed conservation and expanded culture of the bacterial cells, and the expanded bacterial cells were used for plasmid extraction.
  • a control antibody SEQ ID NO: 20 for the light chain, SEQ ID NO: 21 for the heavy chain
  • the viability should be greater than 95%, adjust the HEK293 cell density to 3 ⁇ 10 6 cells/mL with (pre-warmed) HEK293 medium, shake gently and aliquot the cells (the transfection volume is the transfection volume). 90% of the system), note that the volume of cells in the shake flask does not exceed 1/3 of the size of the shake flask, and put it into a shaker for use.
  • the IGF-1R signaling pathway plays an important role in the proliferation, differentiation and metastasis of tumor cells. Activation of IGF-1R can promote the proliferation of certain cells such as MCF7 cells, while inhibition of IGF-1R activity can inhibit cell proliferation. To this end, the activity of the anti-IGF-1R antibody of the present invention can be assessed by detecting the cell proliferation status of MCF7.
  • the CCK8 method was used to detect the inhibitory effect of anti-IGF-1R antibody on the proliferation of MCF7 cells. The brief steps are as follows:
  • Day 1 MCF-7 cells were plated at a density of 5 ⁇ 10 3 /well;
  • the proliferation of MCF7 cells was measured by adding purified chimeric antibodies at different concentrations.
  • the results of inhibition of MCF-7 proliferation by different antibodies are shown in Table 3 below.
  • PHP1003-1 showed better inhibition on the proliferation of MCF7. effect (as shown in Figure 1), the next step will be to further verify the efficacy of the antibody of PHP1003-1.
  • Example 4 The efficacy of antibody PHP1003-1 and control antibody in hyperthyroidism animal model
  • the rat model of hyperthyroidism and thyroid-related ophthalmopathy was induced by intraperitoneal injection of bovine thyroglobulin, and the effect of PHP1003-1 on thyroid-related ophthalmopathy in rats was observed, including the following steps:
  • Rats in the model group were injected intraperitoneally with bovine thyroglobulin (Sigma-Aldrich (Shanghai) Trading Co., Ltd., product number 609310) at a dose of 150 ⁇ g/rat every 2 weeks for modeling, and the modeling was completed for 4 weeks.
  • bovine thyroglobulin Sigma-Aldrich (Shanghai) Trading Co., Ltd., product number 609310
  • Group design normal control group (Sham Group), negative control group (Vehicle Group), test product treatment group (L Group; H Group), control antibody group (P.Group), a total of 5 groups.
  • the specific dosing schedule is operated according to Table 5 below.
  • the muscle fibers were homogeneously stained red, arranged neatly, the intermuscular capillaries were abundant, and the muscle spacing was normal.
  • various extraocular muscle lesions were seen, including severe swelling, degeneration, necrosis, dissolution of muscle fibers, narrowing or widening of muscle spacing, and hyperplasia of connective tissue and blood vessels in intermuscular fibers. It suggested that the SD rat model of thyroid eye disease was successfully established.
  • the visible lesions in the PHP1003-L group basically covered all kinds of lesions in the Vehicle group, and the degree of muscle fiber necrosis and dissolution was slightly less than that in the Vehicle group.
  • the lesions of PHP1003-H group were mild, and the muscle fibers were basically arranged neatly, and some muscle fibers were slightly swollen or degenerated, indicating that the PHP1003-H group had a certain effect on the treatment of thyroid eye disease in SD rats.
  • the results of extraocular muscle staining in group P showed that the degree of swelling, hypertrophy, muscle fiber degeneration and necrosis of the extraocular muscles in the P group were less than those in the Vehicle group.

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Abstract

La présente invention concerne un anticorps qui peut se lier à IGF-1R. L'anticorps est composé d'une chaîne légère et d'une chaîne lourde, et la chaîne légère et la chaîne lourde sont choisies parmi l'une des combinaisons de SEQ ID NO: 70 et SEQ ID NO: 71, SEQ ID NO: 72 et SEQ ID NO: 73, SEQ ID NO: 74 et SEQ ID NO: 75, SEQ ID NO: 76 et SEQ ID NO: 77, SEQ ID NO: 78 et SEQ ID NO: 79, SEQ ID NO : 80 et SEQ ID NO: 81, SEQ ID NO: 82 et SEQ ID NO: 83, et SEQ ID NO: 84 et SEQ ID NO: 85. La présente invention concerne en outre une molécule d'acide nucléique pour le codage de l'anticorps mentionné ci-dessus, un vecteur contenant l'acide nucléique mentionné ci-dessus, une cellule hôte transformée par le vecteur mentionné ci-dessus, et l'utilisation de celui-ci.
PCT/CN2021/132570 2021-04-14 2021-11-23 Anticorps anti-igf-1r et son utilisation Ceased WO2022217923A1 (fr)

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WO2024229406A1 (fr) 2023-05-04 2024-11-07 Revolution Medicines, Inc. Polythérapie pour une maladie ou un trouble lié à ras
WO2025034702A1 (fr) 2023-08-07 2025-02-13 Revolution Medicines, Inc. Rmc-6291 destiné à être utilisé dans le traitement d'une maladie ou d'un trouble lié à une protéine ras
WO2025080946A2 (fr) 2023-10-12 2025-04-17 Revolution Medicines, Inc. Inhibiteurs de ras
WO2025171296A1 (fr) 2024-02-09 2025-08-14 Revolution Medicines, Inc. Inhibiteurs de ras
WO2025240847A1 (fr) 2024-05-17 2025-11-20 Revolution Medicines, Inc. Inhibiteurs de ras
WO2025255438A1 (fr) 2024-06-07 2025-12-11 Revolution Medicines, Inc. Procédés de traitement d'une maladie ou d'un trouble lié à la protéine ras

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CN105315372A (zh) * 2014-06-18 2016-02-10 中国人民解放军军事医学科学院基础医学研究所 一种抗胰岛素样生长因子受体IGF-1R人源抗体LMAb1的制备及应用

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WO2024206858A1 (fr) 2023-03-30 2024-10-03 Revolution Medicines, Inc. Compositions pour induire une hydrolyse de ras gtp et leurs utilisations
WO2024229406A1 (fr) 2023-05-04 2024-11-07 Revolution Medicines, Inc. Polythérapie pour une maladie ou un trouble lié à ras
WO2025034702A1 (fr) 2023-08-07 2025-02-13 Revolution Medicines, Inc. Rmc-6291 destiné à être utilisé dans le traitement d'une maladie ou d'un trouble lié à une protéine ras
WO2025080946A2 (fr) 2023-10-12 2025-04-17 Revolution Medicines, Inc. Inhibiteurs de ras
WO2025171296A1 (fr) 2024-02-09 2025-08-14 Revolution Medicines, Inc. Inhibiteurs de ras
WO2025240847A1 (fr) 2024-05-17 2025-11-20 Revolution Medicines, Inc. Inhibiteurs de ras
WO2025255438A1 (fr) 2024-06-07 2025-12-11 Revolution Medicines, Inc. Procédés de traitement d'une maladie ou d'un trouble lié à la protéine ras

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