38 results about "Eribulin" patented technology

The present invention relates to antibody conjugates which are particularly suitable for targeting cells expressing PTK7, in particular tumor cells. An antibody conjugate according to the present invention has structure (1): AB-[(L6) b-{Z-L-D} x] y (1) wherein AB is an antibody capable of targeting a tumor expressing PTK7; l is a joint connecting Z to D; z is a linking group; l6 is-GlcNAc (Fuc) w-(G) j-S-(L7) w '-wherein G is a monosaccharide, j is an integer in the range of 0 to 10, S is a sugar or a sugar derivative, GlcNAc is N-acetylglucosamine, and Fuc is fucose, w is 0 or 1, w' is 0, 1 or 2, and L7 is-N (H) C (O) CH2-,-N (H) C (O) CF2-or-CH2-; d is selected from the group consisting of an anthracycline, a camptothecin, a tubulysin, an endiyne, an amanitine, a duocarmycin, a maytansinoid, an aurestatin, eribulin, a BCL-XL inhibitor, a miscanthus semiaquilaria, a KSP inhibitor, a TLR agonist, an indolo-benzodiazepine dimer or a pyrrolo-benzodiazepine dimer (PBD), and an analog or prodrug thereof; b is 0 or 1; x is 1 or 2; and y is 1, 2, 3 or 4. The invention further relates to a method for preparing said antibody conjugate of structure (1) and to the use of said antibody conjugate of structure (1).

The present disclosure relates to eribulin derivative drug conjugates, their preparation methods, and their pharmaceutical applications. Specifically, the present disclosure provides antibody-drug conjugates containing an eribulin derivative drug moiety. The present disclosure also relates to methods for treating cancer by administering the antibody-drug conjugates provided herein.

A conjugate of antibody-eribulin or a derivative thereof, an intermediate thereof, a preparation method therefor, a pharmaceutical composition thereof and use thereof. The conjugate of the antibody-eribulin or the derivative thereof provided herein as shown in general formula I is shown below. The conjugate of general formula I has high anti-tumor activity and high stability in circulation, and has excellent tumor tissue targeting property and therapeutic indexes.

The present invention belongs to the field of medicinal chemistry and relates to the preparation of an eribulin intermediate, and specifically to a method for preparing a compound of formula I. The method comprises the following steps: starting from compound 3A or compound 3B, selectively acylating the compound 3A or 3B with a biological enzyme A or selectively hydrolyzing the compound 3B with a biological enzyme B, reacting the hydroxyl group of the desired configuration with the acid anhydride in the presence of an organic base and a catalyst to obtain compound 5, increasing the water solubility of the intermediate product, and separating the two configurations through extraction. The ee value can reach above 99%. The preparation method is simple to operate, has a high conversion rate, good selectivity, low cost, and is conducive to industrial scale-up production.

The present disclosure relates to a pharmaceutical composition containing an eribulin derivative drug conjugate. Specifically, the present disclosure relates to a pharmaceutical composition comprising an antibody drug conjugate and a buffer agent, the antibody drug conjugate has a structure as shown in formula I, and Ab is Pertuzumab. The pharmaceutical composition disclosed by the invention has good stability. # imgabs0 #

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.

An anti-B7H3 antibody-eribulin conjugate of the following formula, a pharmaceutically acceptable salt or solvate thereof, a pharmaceutical composition comprising same, and use thereof. The conjugate is used for preparing a medicament for treating and / or preventing B7H3-mediated diseases or disorders, particularly diseases or disorders with positive B7H3 expression, such as cancer. The anti-B7H3 antibody-eribulin conjugate demonstrates high antigen affinity, strong cellular internalization, significantly improved drug release efficiency, and enhanced killing and inhibition abilities against tumor cells, while maintaining linker stability in plasma and low cytotoxicity. In the formula, TL represents the anti-B7H3 antibody, and n is an integer or decimal of 1-20.

The present invention provides a method for producing an antibody-drug conjugate represented by formula (I) [wherein: Ab represents an antibody or an antigen-binding fragment thereof; D represents eribulin; m is an integer of 1-10; and p is an integer of 1-8], said method comprising step 1 for reacting eribulin or a salt thereof with a compound represented by formula (A) [wherein: m is an integer of 1-10; and X represents a phenoxy group or a nitrophenoxy group] to give a compound represented by formula (B) [wherein m is an integer of 1-10], and step 2 for reacting the compound represented by formula (B) with the Ab to give the antibody-drug conjugate represented by formula (I).　

In the present invention, the combined administration of a liposomal composition containing eribulin or a pharmaceutically acceptable salt thereof and a PD-1 antagonist shows an unexpected antitumor effect.

The present application relates to the technical field of medicines, and in particular to an eribulin derivative and an antibody-drug conjugate (ADC) thereof, and a medical use thereof. In the present application, a series of derivatives with good tumor suppression effects are synthesized by modifying eribulin, and have lower toxicity and a larger therapeutic window than that of eribulin; and then the the eribulin derivative and an antibody are made into an ADC by means of an appropriate linker, and the therapeutic efficiency of the eribulin derivative is improved using the targeting specificity of the antibody.

An antibody drug conjugate, and uses and methods of preparation thereof are provided. Particularly, the invention provides a hydrophilic linker which can meet the connection of drug molecules, and the obtained antibody drug conjugate has better stability and hydrophilicity and good pharmacokinetic properties.

A compound as shown in the following formula (I) and its racemate, stereoisomer, tautomer, isotopically labeled, nitroxide, solvate, polymorph or pharmaceutically acceptable salt thereof, the compound is an analogue of eribulin, has good anticancer activity, can overcome multiple drug resistance and maintain high cytotoxicity.

Linker toxins and antibody-drug conjugates that bind to human oncology antigen targets such as folate receptor alpha and / or provide anti-tubulin drug activity are disclosed. The linker toxins and antibody-drug conjugates comprise an eribulin drug moiety and can be internalized into target antigen-expressing cells. The disclosure further relates to methods and compositions for use in the treatment of cancer by administering the antibody-drug conjugates provided herein.

Provided are an anti-CD79B antibody-drug conjugate, and a preparation method therefor and pharmaceutical use thereof. In particular, provided are an antibody-drug conjugate (ADC) which comprises an anti-CD79B antibody conjugated with an MMAE or a derivative thereof, exatecan or a derivative thereof, or Eribulin or a derivative thereof, a pharmaceutical composition containing the ADC, and use thereof in preparation of a drug for treatment of a CD79B-mediated disease or disorder, especially use thereof in preparation of an anti-cancer drug.

The present invention relates to a process for the preparation of high pure Eribulin and Eribulin Mesylate. The present invention involves preparation of high pure Eribulin and its mesylate salt involving chiral acid addition salts of Eribulin.

The invention discloses an antibody-coupled drug intermediate SET0575 and a preparation method and application thereof, the chemical structural formula of the antibody-coupled drug intermediate SET0575 is as follows: a high-activity drug Eribulin can be coupled to an antibody at a fixed point, and meanwhile, the connexon has good plasma stability, can avoid splitting decomposition of ADC drugs in blood circulation, reduce toxic and side effects of ADC and improve safety.

A dual-toxin antibody-drug conjugate and the pharmaceutical use thereof. The dual-toxin antibody-drug conjugate containing an eribulin compound and a camptothecin compound has a good tumor inhibitory activity and a synergistic tumor inhibitory effect between toxins.

Provided is a pharmaceutical composition of an anti-ROR1 antibody-drug conjugate. The pharmaceutical composition comprises an anti-ROR1 antibody-drug conjugate, a buffer, a stabilizer, and a surfactant. The anti-ROR1 antibody comprises a first antigen-binding domain and a second antigen-binding domain. The drug is Eribulin, which is linked to the anti-ROR1 antibody by means of a linker. By optimizing the component ratio and the preparation process, the pharmaceutical composition of the anti-ROR1 antibody-drug conjugate exhibits excellent physical and chemical stability, ensuring that the anti-ROR1 antibody-drug conjugate can maintain a stable effect under long-term storage conditions.

The present invention concerns antibody-conjugates which are especially suitable for the targeting of PTK7-expressing cells, in particular tumour cells. The antibody-conjugates according to the invention have structure (1):AB-[(L6)b-{Z-L-D}x]y  1Herein, AB is an antibody capable of targeting PTK7-expressing tumours; L is a linker that links Z to D; Z is a connecting group; L6 is -GlcNAc(Fuc)w-(G)j-S-(L7)w′-, wherein G is a monosaccharide, j is an integer in the range of 0-10, S is a sugar or a sugar derivative, GlcNAc is N-acetylglucosamine and Fuc is fucose, w is 0 or 1, w′ is 0, 1 or 2 and L7 is —N(H)C(O)CH2—, —N(H)C(O)CF2— or —CH2—; D is selected from the group consisting of anthracyclines, camptothecins, tubulysins, enediynes, amanitins, duocarmycins, maytansinoids, auristatins, eribulins, BCL-XL inhibitors, hemiasterlins, KSP inhibitors, TLR agonists, indolinobenzodiazepine dimers or pyrrolobenzodiazepine dimers (PBDs), and analogues or prodrugs thereof; b is 0 or 1; x is 1 or 2; and y is 1, 2, 3 or 4. The invention further concerns a method for preparing the antibody-conjugates of structure (1) and application of the antibody-conjugates of structure (1).

Antibodies, antigen-binding fragments, and conjugates (e.g., antibody-drug conjugates such as those comprising eribulin) thereof that bind to mesothelin are disclosed. The disclosure further relates to methods and compositions for use in the treatment of cancer by administering the compositions provided herein.

The present invention provides methods of treating various cancers using an antibody-conjugated drug (ADC) Ab-(L-D) p, or a composition thereof, where Ab is an anti-HER2 antibody moiety (e.g., an antibody having the same structure as trastuzumab), L is a cleavable linker comprising Mal-(PEG) 2-Val-Cit-pAB, D is esculentin, and p is an integer from 1 to 8, including terminal values.

The invention discloses an antibody-drug conjugate targeting TROP2 as well as a preparation method and application of the antibody-drug conjugate. The TROP2-targeting antibody-drug conjugate has a structure as shown in a formula I. According to the invention, cytotoxins MMAE, Eribulin and the like are specifically connected to antibody glycosylation sites by using a sugar site-specific technology, and the obtained ADC compound has good in-vitro homogeneity and toxicity for TROP2 positive cells, and can be used for preparing antitumor drugs for TROP2 positive tumors. # imgabs0 #

An anti-B7H3 antibody-eribulin conjugate formulation, a preparation method therefor, and use thereof. The formulation contains trehalose, polysorbate 20, histidine, histidine hydrochloride, and an anti-B7H3 antibody-eribulin conjugate or a pharmaceutically acceptable salt or solvate thereof. A specific formulation formula is designed for the anti-B7H3 antibody-eribulin conjugate. By means of using the synergistic cooperation of specific component excipients and a buffer system, the stability of the formulation is significantly improved. Moreover, the preparation process is further verified scientifically and systematically, which proves that the well-developed anti-B7H3 antibody-eribulin conjugate formulation and the preparation process thereof maintain the purity, coupling rate, and free drug of the finished product stable, reduce molecular degradation and aggregates, have strong process stability, and can be applied on a large scale, thereby promoting the application of the anti-B7H3 antibody-eribulin conjugate.

Disclosed are a TROP2-targeted antibody-drug conjugate (ADC), and a preparation method therefor and a use thereof. The TROP2-targeted ADC has a structure as shown in formula I. In the present invention, glycosyl site-directed technology is used to specifically link the cell toxins MMAE and Eribulin, and the like to an antibody glycosylation site, and an obtained ADC compound has good in-vitro uniformity and toxicity for TROP2-positive cells, and can be used for preparing anti-tumor drugs for TROP2-positive tumors.

To provide an antibody-drug conjugate for treating and / or preventing cancer.SOLUTION: The present disclosure relates to a drug conjugate of an Eribulin derivative, a preparation method therefor and an application thereof in medicine. Specifically, provided is an antibody-drug conjugate, which contains an Eribulin derivative drug portion having a linker containing a peptide portion cleavable by an enzyme.SELECTED DRAWING: None

The invention relates to an eribulin derivative, a preparation method thereof and application of the eribulin derivative in medicine. Specifically, the invention relates to an eribulin derivative as shown in a general formula (I), a preparation method thereof, a pharmaceutical composition containing the derivative and application of the eribulin derivative as a therapeutic agent, especially application of the eribulin derivative in preparation of drugs for treating and / or preventing cancers.

The present invention concerns antibody-conjugates which are especially suitable for the targeting of PTK7-expressing cells, in particular tumour cells. The antibody-conjugates according to the invention have structure (1):Herein, AB is an antibody capable of targeting PTK7-expressing tumours; L is a linker that links Z to D; Z is a connecting group; L6 is -GlcNAc(Fuc)w-(G)j-S-(L7)w′-, wherein G is a monosaccharide, j is an integer in the range of 0-10, S is a sugar or a sugar derivative, GlcNAc is N-acetylglucosamine and Fuc is fucose, w is 0 or 1, w′ is 0, 1 or 2 and L7 is —N(H)C(O)CH2—, —N(H)C(O)CF2— or —CH2—; D is selected from the group consisting of anthracyclines, camptothecins, tubulysins, enediynes, amanitins, duocarmycins, maytansinoids, auristatins, eribulins, BCL-XL inhibitors, hemiasterlins, KSP inhibitors, TLR agonists, indolinobenzodiazepine dimers or pyrrolobenzodiazepine dimers (PBDs), and analogues or prodrugs thereof; b is 0 or 1; x is 1 or 2; and y is 1, 2, 3 or 4. The invention further concerns a method for preparing the antibody-conjugates of structure (1) and application of the antibody-conjugates of structure (1).