108 results about "HER2 Antibody" patented technology

The present disclosure relates HER2 antibodies and to the de novo design of structure-based design targeted antibodies. According to the current disclosure, computer-implemented methods of designing an antibody sequences that will bind the HER2 with significant affinity at a target receptor epitope are disclosed. The method utilizes artificial intelligence (Al) and machine learning (ML) models that are trained to predict improved biomolecule (e.g., antibody or antibody fragments) binding sequences or other desirable properties using known biomolecule / binding partner complexes. A designed HER2 antibody is generated by replacing matching residues with different residues such that a predicted affinity is increased.

Belongs to the field of biological medicine, and relates to application of an anti-HER2 antibody drug conjugate to treatment of HER2 negative breast cancer. The invention also relates to application of the anti-HER2 antibody drug conjugate in preparation of a drug for treating HER2 negative breast cancer of a subject. The invention also relates to a method for treating HER2-negative breast cancer in a subject. The method comprises the step of administering the anti-HER2 antibody drug conjugate to the subject. The method is beneficial to HER2 negative breast cancer subjects, and has good safety.

The present invention relates to a highly concentrated, stable pharmaceutical formulation of a pharmaceutically active anti-HER2 antibody, such as e.g. Trastuzumab (HERCEPTIN™), Pertuzumab or T-DM1, or a mixture of such antibody molecules for subcutaneous injection. In particular, the present invention relates to formulations comprising, in addition to a suitable amount of the anti-HER2 antibody, an effective amount of at least one hyaluronidase enzyme as a combined formulation or for use in form of a co-formulation. The formulations comprise additionally at least one buffering agent, such as e.g. a histidine buffer, a stabilizer or a mixture of two or more stabilizers (e.g. a saccharide, such as e.g. α,α-trehalose dihydrate or sucrose, and optionally methionine as a second stabilizer), a nonionic surfactant and an effective amount of at least one hyaluronidase enzyme. Methods for preparing such formulations and their uses thereof are also provided.

Provided herein are methods for treating or preventing progression of cancer in an individual, comprising administering to the individual an effective amount of an anti-PD-1 antibody, e.g., toripalimab, and an anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugate that comprises an anti-HER2 antibody and a cytotoxic molecule. Compositions, uses, and kits related thereto are also provided.

An anti-HER2 antibody-drug conjugate for treating intestinal cancer in a subject. A use of the anti-HER2 antibody-drug conjugate in the preparation of a drug for treating intestinal cancer in a subject.

The present invention provides an antibody-drug conjugate, a preparation method thereof, and an application thereof. The structural formula of the antibody-drug conjugate is as follows. Among them, mAb is the anti-HER2 antibody trastuzumab; the conjugate is obtained by Michael addition of the thiol group obtained by reducing the inter-chain disulfide bond of mAb with the linker-irinotecan conjugate LD038; n ranges from 1 to 10. The binding activity and internalization activity of the antibody-drug conjugate to various tumor target cells are not affected; compared with the same type of antibody-drug conjugate, the antibody-drug conjugate PRO1102 synthesized by the preparation method of the antibody-drug conjugate of the present invention shows certain advantages in terms of in vitro cytotoxicity to tumor cells, anti-tumor activity in rats in vivo, and in vivo pharmacokinetics.

The present invention refers to the combination of the HER2 tyrosine kinase inhibitor zongertinib with an anti-HER2 antibody and / or an anti-HER2 antibody-drug conjugate. Such combination may further comprise an additional anti-cancer medicament. The combination of the invention is useful for the treatment and / or prevention of oncological and / or hyperproliferative diseases, such as cancer. Accordingly, compounds for use, methods of prevention and / or treatment, uses, pharmaceutical compositions and kits related to the combination are herewith provided.

The present application provides antibodies comprising an antigen-binding fragment of an anti-CD3 antibody having tailor-made affinity to CD3 in low to medium range. In some embodiments, the antibody further comprises an antigen-binding fragment that specifically binds to a target antigen, such as HER2, CD20, TROP2, BCMA, or CD19. Also provided are anti-CD3 antibodies, masked anti-CD3 antibodies (including activatable anti-CD3 antibodies), anti-CD20 antibodies, and masked anti-HER2 antibodies (including activatable anti-HER2 antibodies). The antibodies described herein are useful for treatment of cancer.

The present invention relates to the treatment of HER2 mutated cancers by administering an anti-HER2 antibody-drug conjugate. The present invention relates to a therapeutic agent for HER2 mutated cancer, and more specifically, to a therapeutic agent for HER2 mutated cancer comprising, as an active ingredient, an anti-HER2 antibody-drug conjugate in which a drug-linker represented by the following formula (wherein A represents a connection position to an anti-HER2 antibody) is conjugated to an antibody through a thioether bond, and / or to a method for treating cancer, the present invention also relates to a method for preparing the anti-HER2 antibody-drug conjugate, which comprises administering the anti-HER2 antibody-drug conjugate to a subject having a cancer determined to have an HER2 mutation. # imgabs0 #

The present application describes uses for Pertuzumab, a first-in-class HER2 dimerization inhibitor. In particular, the application describes methods for extending progression free survival in a HER2-positive breast cancer patient population; and combining two HER2 antibodies to treat HER2-positive cancer without increasing cardiac toxicity.

The invention provides a simple and rapid preparation method of a novel HER2 targeted nano-drug maytansine (DM1). The preparation of the nano-drug is realized by using carboxyl on a side chain of azide-terminated poly (L-glutamic acid) (PLG) as a load binding site. The preparation method comprises the following steps: firstly, grafting N-(2-aminoethyl) maleimide hydrochloride (Mal-C2H4-NH2-HCL) to carboxyl of PLG (Poly L-Glycol), and introducing a maleimide group to form PLG-Mal; the preparation method comprises the following steps: preparing Fc-III-4C peptide-PLG-Mal (Fc-PLG-Mal) by virtue of an amidation reaction between carboxyl and amino of the Fc-III-4C peptide, and then carrying out thiol-maleimide click chemical reaction on a maleimide group and sulfydryl of DM1, so as to obtain the Fc-PLG-DM1. Finally, the HER2 antibody and the Fc-PLG-DM1 are mixed in water by utilizing the high affinity effect between the Fc-III-4C peptide and the Fc segment of the HER2 antibody, so that the HER2-PLG-DM1 can be obtained, and the HER2-PLG-DM1 has a remarkable tumor inhibition effect in animal experiments. The successful development of the HER2-PLG-DM1 proves the potential of the method in the design and development of functional nano-drugs in the future.

The present application relates to the technical field of antibodies, in particular to HER2 antibodies or antigen-binding fragments thereof. The present application provides HER2 antibodies or antigen-binding fragments thereof, wherein the heavy chain comprises at least one mutation: CDR1 is mutated to T5M in the wild-type fragment of SEQ ID NO. 1, D6G mutation, or CDR2 is mutated to G7V in the wild-type fragment of SEQ ID NO. 2. The antibody has high affinity to HER2 S310F / Y The mutant target has the recognition ability and maintains the functional activity to the wild-type HER2.

A pharmaceutical product for administration of an anti HER2 antibody-drug conjugate in combination with an ATR inhibitor is provided. The anti-HER2 antibody-drug conjugate is an antibody-drug conjugate in which a drug linker represented by the following formula (wherein A represents the connecting position to an antibody) is conjugated to an anti-HER2 antibody via a thioether bond. Also provided is a therapeutic use and method wherein the antibody-drug conjugate and the ATR inhibitor are administered in combination to a subject: Formula (I):

Disclosed are new anti-HER2 ADCs conjugated to camptothecin derivatives as toxins for therapeutic use. The antitumor effects of the ADCs of Formula (PL-A) (e.g., compounds MB-2a and MB-3a (trastuzumab meditecan)) render these compounds useful for treating cell proliferative diseases such as cancers.

Disclosed are new anti-HER2 ADCs conjugated to camptothecin derivatives as toxins for therapeutic use. The antitumor effects of the ADCs of Formula (PL-A) (e.g., compounds MB-2a and MB-3a (trastuzumab meditecan)) render these compounds useful for treating cell proliferative diseases such as cancers.

The application belongs to the field of biology and relates to a nucleic acid molecule encoding an anti-HER2 antibody, a vector containing the nucleic acid molecule and an expression method, wherein the nucleic acid molecule contains codons optimized for expression cells. By using the nucleic acid molecule of the application, the expression amount of the anti-HER2 antibody in cells can be improved, the yield of the anti-HER2 antibody is increased, and the production cost is reduced; and the anti-HER2 antibody produced has similar performance to that of the original research drug and has a good drug-making prospect.

The invention provides a preparation method of HER2 targeted composite nanoparticles conjugated with a blood vessel disrupting agent, which comprises the following steps: grafting water-soluble azide-terminated poly (L-glutamic acid) with methoxy polyethylene glycol (NPLG-g-mPEG) to increase the number of effective load binding sites, bonding a cytotoxic drug SN38 with NPLG-g-mPEG through Steglich esterification reaction to obtain N3-PLG-SN38, and then adding the N3-PLG-SN38 into the HER2 targeted composite nanoparticles conjugated with the blood vessel disrupting agent to obtain the HER2 targeted composite nanoparticles conjugated with the blood vessel disrupting agent. According to the present invention, the Fc-PLG-SN38 is obtained by carrying out click chemical bonding on the Fc-III-4C peptide and the N3-PLG-SN38, by using the high affinity between the Fc-III-4C peptide and the Fc of the HER2 antibody, the antibody and the Fc-NPLG-SN38 are mixed in the water environment so as to obtain the HER2-PLG-SN38, and the HER2-PLG-SN38 and the blood vessel disrupting agent CA4P are conjugated so as to enhance the penetrating power and the drug effect on tumor cells;

The present invention refers to the combination of the HER2 tyrosine kinase inhibitor zongertinib with an anti-HER2 antibody and / or an anti-HER2 antibody-drug conjugate. Such combination may further comprise an additional anti-cancer medicament. The combination of the invention is useful for the treatment and / or prevention of oncological and / or hyperproliferative diseases, such as cancer. Accordingly, compounds for use, methods of prevention and / or treatment, uses, pharmaceutical compositions and kits related to the combination are herewith provided.

The present disclosure pertains to the field of biomedicines and relates to use of an anti-HER2 antibody-drug conjugate in the treatment of biliary tract cancer. The present disclosure also relates to use of an anti-HER2 antibody-drug conjugate in the preparation of a medicament for treating biliary tract cancer in a subject. The present disclosure also relates to a method for treating biliary tract cancer in a subject, the method comprising administering an anti-HER2 antibody-drug conjugate to the subject. The method provides benefits for subjects with biliary tract cancer and has good safety.

This disclosure pertains to the field of biomedicine and relates to the use of an anti-HER2 antibody-drug conjugate (ADC) for the treatment of breast cancer. It also relates to a method for treating a subject with breast cancer, the method comprising administering an anti-HER2 antibody-drug conjugate to the subject. Furthermore, it relates to the use of the anti-HER2 antibody-drug conjugate in the preparation of a medicament for neoadjuvant therapy of breast cancer. The method provides benefit to breast cancer subjects and has a good safety profile.

The application belongs to the field of biological medicine, and relates to the use of an anti-HER2 antibody drug conjugate for treating breast cancer. The application also relates to the use of an anti-HER2 antibody drug conjugate in the preparation of a medicament for treating breast cancer in a subject. The application also relates to a method for treating breast cancer in a subject, which comprises administering an anti-HER2 antibody drug conjugate to the subject. The method is beneficial to the breast cancer subject, and has good safety.

Provided are a humanized / fully human HER2 antibody or an antigen-binding fragment thereof, and an antibody-radionuclide conjugate using same as a targeting group for radioactive labeling, showing a tumor-targeting enrichment ability.

The present invention provides a use of an Eribulin derivative drug conjugate in the treatment of a tumor. Particularly, the present invention provides a use of a compound as represented by formula IA or a pharmaceutically acceptable salt thereof in the preparation of a drug for treating a tumor disease resistant to an anti-HER2 antibody-drug conjugate.

Provided are methods for treating or preventing progression of cancer in an individual, comprising administering to the individual an effective amount of an anti-PD-1 antibody, e.g., toripalimab, and an anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugate that comprises an anti-HER2 antibody and a cytotoxic molecule. Compositions, uses, and kits related thereto are also provided.

The present invention belongs to the field of biology, and relates to a nucleic acid molecule encoding an anti-HER2 antibody, a vector comprising the nucleic acid molecule, and an expression method wherein the nucleic acid molecule comprises codons optimized for expression cells. By utilizing the nucleic acid molecule disclosed by the invention, the expression quantity of the anti-HER2 antibody in cells can be increased, the yield of the anti-HER2 antibody is increased, and the production cost is reduced; and the produced anti-HER2 antibody is similar to an original research drug in performance and has a relatively good patent medicine prospect.

The present disclosure relates to a novel anti-HER2 antibody or an antigen-binding fragment thereof used in the prevention or treatment of cancer, a chimeric antigen receptor including the same, and uses thereof. The antibody of the present disclosure is an antibody that specifically binds to HER2 which is highly expressed in cancer cells (particularly, breast cancer or gastric cancer cells), and binds to an epitope that is different from an epitope to which trastuzumab binds.

A pharmaceutical composition characterized in that a combination of an (anti-HER2 antibody)-drug conjugate and a HER dimerization inhibitor is administered, in which the (anti-HER2 antibody)-drug conjugate comprises a drug linker represented by the formula shown below (wherein A represents a binding position to an anti-HER2 antibody) and an anti-HER2 antibody bonded to each other through a thioether bond; and / or a treatment method characterized in that a combination of the (anti-HER2 antibody)-drug conjugate and the HER dimerization inhibitor is administered to an individual.

A pharmaceutical product for administration of an anti- HER2 antibody-drug conjugate (ADC) in combination with an anti-TROP2 ADC is provided. The anti-HER2 ADC and the anti-TROP2 ADC comprise a drug-linker. An exatecan may be the drug of the drug-linker and the drug-linker may be conjugated to the respective antibody via a thioether bond. Also provided is a therapeutic use and method in which the anti-HER2 ADC and the anti-TROP2 ADC are administered in combination to a subject. The anti-HER2 ADC and anti-TROP2 ADC in combination have excellent anti-cancer properties.

The present invention relates to a highly concentrated, stable pharmaceutical formulation of a pharmaceutically active anti-HER2 antibody, such as e.g. Trastuzumab (HERCEPTIN™), Pertuzumab or T-DM1, or a mixture of such antibody molecules for subcutaneous injection. In particular, the present invention relates to formulations comprising, in addition to a suitable amount of the anti-HER2 antibody, an effective amount of at least one hyaluronidase enzyme as a combined formulation or for use in form of a co-formulation. The formulations comprise additionally at least one buffering agent, such as e.g. a histidine buffer, a stabilizer or a mixture of two or more stabilizers (e.g. a saccharide, such as e.g. α,α-trehalose dihydrate or sucrose, and optionally methionine as a second stabilizer), a nonionic surfactant and an effective amount of at least one hyaluronidase enzyme. Methods for preparing such formulations and their uses thereof are also provided.

The invention provides an anti-HER2 antibody or an antigen binding fragment thereof, an anti-HER2 complementary bispecific antibody and a complementary bispecific antibody-drug conjugate (ADC) constructed by the anti-HER2 antibody or the antigen binding fragment, and a pharmaceutical composition and a kit containing the anti-HER2 antibody or the antigen binding fragment. Also provided are methods of using the antibodies, ADCs, pharmaceutical compositions and kits for treating diseases associated with abnormal expression of HER2.