13 results about "Pyroglutamic acid" patented technology

To provide antibodies and antigen binding fragments thereof that are useful for diagnosis, prognosis and treatment of Alzheimer's disease or other β-amyloid-related diseases, and methods of making and using the antibodies or antigen binding fragments thereof.SOLUTION: The present invention provides an isolated monoclonal antibody or antigen-binding fragment thereof, comprising a heavy chain complementarity determining region 1 (HCDR1), HCDR2, HCDR3, a light chain complementarity determining region 1 (LCDR1), LCDR2, and LCDR3, having specific polypeptide sequences, wherein the antibody or antigen-binding fragment thereof specifically binds 3pE Ab, preferably human 3pE Ab.SELECTED DRAWING: None

The present invention relates to a method for the purification of immunoglobulins comprising N- terminal glutamine. In particular, the method comprises an incubation step embedded in a sequence of chromatographic methods comprising a capture step, an intermediate chromatography step, and a polishing step. The implementation of an incubation step embedded in the sequence of chromatographic purification methods promotes the conversion of N-terminal glutamine to pyro glutamate, thereby reducing the amount of N-terminal glutamine to be depleted by cation exchange chromatography while overall product yield is increased. In addition, the incubation may be conducted prior or following the intermediate chromatography step.

The present disclosure provides a bispecific binding molecule, which binds to AβpE3, i.e. to an N-terminally truncated and pyroglutamate-modified form of amyloid beta (Aβ), and to the protease-like domain of human transferrin receptor 1 (hTfR1), as well as therapeutic and diagnostic uses thereof.

A tegoprazan pyroglutamate injection consisting of an active ingredient tegoprazan pyroglutamate and an alcohol solvent, and a preparation method therefor. The injection has relatively high stability.

The invention discloses a freeze-drying preparation method of tegorasone pyroglutamate, which adopts a freeze-drying method to prepare a tegorasone pyroglutamate compound, solves the problems that the solvent residue is difficult to remove and the clarity is unqualified in the process of preparing the tegorasone pyroglutamate by a solvent method, improves the product yield and purity, and has the advantage of environmental protection. The method is suitable for commercial production.

Deposition of N-terminally truncated and pyroglutamate-modified Abeta peptides (AβpE3) play an important role in the aggregation of the amyloid-β (Aβ) protein in the brain. The N-terminally truncated and pyroglutamate-modified Abeta peptides, therefore, can be a suitable target for the prevention and treatment of Alzheimer's Disease (AD). Disclosed herein are antibodies and fragments having excellent specificity to N-terminally truncated and pyroglutamate-modified Abeta peptides, as well as uses of these antibodies and fragments for the prevention and treatment of AD.

The present disclosure provides a bispecific binding molecule, which binds to AβpE3, i.e. to an N-terminally truncated and pyroglutamate-modified form of amyloid beta (Aβ), and to the protease-like domain of human transferrin receptor 1 (hTfR1), as well as therapeutic and diagnostic uses thereof.

The invention belongs to the field of pharmaceutical preparations, and relates to a freeze-dried composition of tigorasone pyroglutamate and a preparation method of the freeze-dried composition. The freeze-dried composition is prepared from tigorasone pyroglutamate, mannitol and tert-butyl alcohol. The prepared product is stable after being redissolved, the product quality is improved, and the adopted preparation method is simple, controllable in operation and suitable for industrial mass production.

The application relates to a pyroglutamate A beta-targeted single-domain antibody and a preparation method and application thereof, the amino acid sequence of the single-domain antibody is shown in SEQ ID NO. 1 or SEQ ID NO. 2 or SEQ ID NO. 3 or SEQ ID NO. 4 or SEQ ID NO. 5 or SEQ ID NO. 6 or SEQ ID NO. 7 or SEQ ID NO. 8; a striped banded dogfish is taken as an immunization object, PE-A beta is taken as an antigen for immunization, total RNA of peripheral blood cells of the immunized dogfish is extracted, reverse transcription is carried out to obtain cDNA, amplification is carried out by taking the cDNA as a template, a phagemid carrier is constructed by taking the amplification as a template, the phagemid carrier is transferred into a competent cell, the competent cell is cultured, positive clones are screened, and the single-domain antibody is obtained. The single-domain antibody provided by the application can specifically recognize PEA beta, has good binding activity, has a small molecular weight, solves the technical problem that no shark nanobody targeting PEA beta has been found at present, lays an important foundation for subsequent research on the application of the antibody in the detection of PEA beta, and has application prospects in the development of a reagent for detecting PEA beta or a drug for treating PEA beta-related diseases.

The present disclosure relates to anti-amyloid beta peptide antibodies that specifically bind N-terminal truncated pyroglutamate amyloid beta peptide (pyroGlu3 Abeta (Ab)), multi-specific binding proteins comprising a pyroGlu3 Abeta (Ab) antigen-binding domain and a blood brain barrier (BBB) antigen-binding domain that specifically binds to a BBB target selected from human transferrin receptor (TfR) or human CD98 heavy chain (CD98hc), and uses (e.g., therapeutic uses) thereof.

The invention provides a preparation method of an AT-406 intermediate, and belongs to the technical field of medical intermediates. According to the method, methyl L-pyroglutamate is subjected to ethynylation, and a selected ester solvent and a hydroboration reagent are subjected to hydroboration reductive amination reaction, so that the reaction selectivity can be improved, isomer impurities are reduced, separation and purification are easy, a single cis-configuration product can be obtained, and the ee value can reach 99.5% or above. The specific hydroboration reagent and the oxidation reagent are selected, so that the use of ozone and reagents with strong mercaptan odor is avoided, the selectivity of intramolecular reaction is improved, the generation of byproducts is reduced, separation and purification are easy, the catalyst and the byproducts are non-toxic and pollution-free to the environment, and the method is suitable for industrial production. The invention provides a method suitable for industrial production to obtain the AT-406 intermediate.

An antibody conjugate comprising three small chain variable light and heavy antibody fragments (scFv) joined together by a cleavable linker and further fused with transferrin protein with a cleavable linker to bind soluble amyloid-beta protofibrils, a specific pyroglutamate-modified form of amyloid-beta called N3pG, and aggregated forms of amyloid-beta, to treat Alzheimer's disease.

This invention discloses a method for synthesizing chiral δ-caprolactam compounds. Using N-Boc-L-pyroglutamate as a starting material, intermediate II is obtained through nucleophilic ring-opening with a Grignard reagent. This intermediate is then subjected to enamidation of a ketone and cyclization with a lactam to form intermediate III. Halogenation of intermediate III yields intermediate IV, which is then coupled with a metal-catalyzed reaction to obtain intermediate V. By controlling the chirality at the C-3 position of intermediate V and catalytically reducing the C5-C6 carbon-carbon double bond, chiral intermediate VI is obtained. Intermediate VI undergoes trifluoroethylation and crystallization-induced diastereomeric transformation to prepare the key aminolactam intermediate A for the drug ubrogepant. This invention avoids the chiral resolution by high-performance liquid chromatography, the high technical barriers of transaminase catalysis, and the cumbersome salt-forming resolution process, thus improving the synthetic efficiency of chiral δ-caprolactam compounds and possessing significant industrial application value.