Patents by Inventor Zhengjian Li
Zhengjian Li has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Patent number: 12357965Abstract: The present invention provide novel immunofiber compositions for protein or peptide purification and simple and cost-efficient methods and systems using these compositions. In some embodiments, the immunofibers comprise a customized Z-33 peptide derived from Staphylococcus aureus Protein A which is used to construct immuno-amphiphile molecules that assemble into immunofibers in aqueous solution with bioactive epitopes on the surface and have peptide or protein binding ability.Type: GrantFiled: September 1, 2023Date of Patent: July 15, 2025Assignees: The Johns Hopkins University, Bristol-Myers Squibb CompanyInventors: Honggang Cui, Yi Li, Lye Lin Lock, XuanKuo Xu, Zhengjian Li
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Patent number: 12325875Abstract: The present disclosure relates to the use of host cell protein biomarkers to assess disulfide bond reduction in compositions comprising a protein of interest. In some embodiments, the disclosure relates to methods of predicting the occurrence of disulfide bond reduction or low molecular weight protein species in compositions comprising a protein of interest, wherein the expression or activity level of at least one host cell protein is measured and provides a benchmark value associated with the occurrence of disulfide bond reduction or low molecular weight species of said protein of interest. In some embodiments, the disclosure relates to methods of producing a protein of interest, wherein host cells capable of producing the protein of interest are cultured, the expression or activity level of at least one host cell protein is measured, and downstream isolation of the protein of interest is informed by the host cell protein measurements.Type: GrantFiled: March 15, 2019Date of Patent: June 10, 2025Assignee: Bristol-Myers Squibb CompanyInventors: Anthony Joseph Cura, Xuankuo Xu, Zhengjian Li, Sanchayita Ghose, Susan Egan
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Patent number: 12174161Abstract: In certain embodiments, the present invention provides a method of measuring the level of hydrophobicity of a chromatographic resin. In certain embodiments, the present invention provides a method of selecting a chromatographic resin condition for purifying a protein of interest from a mixture, wherein the protein of interest has low or no aggregation formation during chromatography. In certain embodiments, the present invention provides a method of selecting a chromatographic resin from a plurality of chromatographic resins for purifying a protein of interest from a mixture, wherein the protein of interest has low or no aggregation formation during chromatography.Type: GrantFiled: March 27, 2020Date of Patent: December 24, 2024Assignee: BRISTOL-MYERS SQUIBB COMPANYInventors: Chao Huang, Joseph James Perry, Xuankuo Xu, Sanchayita Ghose, Zhengjian Li, Weixin Jin
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Publication number: 20240082816Abstract: The present invention provide novel immunofiber compositions for protein or peptide purification and simple and cost-efficient methods and systems using these compositions. In some embodiments, the immunofibers comprise a customized Z-33 peptide derived from Staphylococcus aureus Protein A which is used to construct immuno-amphiphile molecules that assemble into immunofibers in aqueous solution with bioactive epitopes on the surface and have peptide or protein binding ability.Type: ApplicationFiled: September 1, 2023Publication date: March 14, 2024Inventors: Honggang Cui, Yi Li, Lye Lin Lock, XuanKuo Xu, Zhengjian Li
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Publication number: 20240051989Abstract: In some embodiments, the present invention provides a method of purifying a protein of interest with a reduced level of aggregation formation in cation exchange (CEX) chromatography, comprising: (a) providing a mixture comprising the protein of interest and one or more contaminants; (b) loading the mixture onto a CEX resin coupled with arginine; and (c) eluting the protein of interest from the resin, thereby purifying the protein of interest with a reduced level of aggregation formation in CEX chromatography.Type: ApplicationFiled: October 27, 2023Publication date: February 15, 2024Applicant: BRISTOL-MYERS SQUIBB COMPANYInventors: Zhengjian LI, Xuankuo XU, Chao HUANG, Zhiqiang CHEN
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Patent number: 11840554Abstract: In some embodiments, the present invention provides a method of purifying a protein of interest with a reduced level of aggregation formation in cation exchange (CEX) chromatography, comprising: (a) providing a mixture comprising the protein of interest and one or more contaminants; (b) loading the mixture onto a CEX resin coupled with arginine; and (c) eluting the protein of interest from the resin, thereby purifying the protein of interest with a reduced level of aggregation formation in CEX chromatography.Type: GrantFiled: February 10, 2021Date of Patent: December 12, 2023Assignee: BRISTOL-MYERS SQUIBB COMPANYInventors: Zhengjian Li, Xuankuo Xu, Chao Huang, Zhiqiang Chen
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Patent number: 11745165Abstract: The present invention provide novel immunofiber compositions for protein or peptide purification and simple and cost-efficient methods and systems using these compositions. In some embodiments, the immunofibers comprise a customized Z-33 peptide derived from Staphylococcus aureus Protein A which is used to construct immuno-amphiphile molecules that assemble into immunofibers in aqueous solution with bioactive epitopes on the surface and have peptide or protein binding ability.Type: GrantFiled: August 17, 2018Date of Patent: September 5, 2023Assignees: THE JOHNS HOPKINS UNIVERSITY, BRISTOL-MYERS SQUIBB COMPANYInventors: Honggang Cui, Yi Li, Lye Lin Lock, XuanKuo Xu, Zhengjian Li
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Publication number: 20230129707Abstract: In one aspect, a method for automated analysis of samples from a bioreactor is provided herein, the method including: drawing at least one sample from a bioreactor; pressurizing the drawn at least one sample into a sample flow; purifying at least one target protein in the sample flow using a first liquid chromatography apparatus to create a purified sample flow; splitting the purified sample flow into a purified sample fraction flow and an effluent flow; and, analyzing the at least one target protein in the purified sample fraction flow using a second liquid chromatography apparatus. Advantageously, the subject invention provides for an automated two-step liquid chromatography process utilizing first dimension liquid chromatography for purification and second dimension liquid chromatography for analysis.Type: ApplicationFiled: June 29, 2021Publication date: April 27, 2023Inventors: Letha Chemmalil, Julia Ding, Zhengjian Li
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Publication number: 20230076713Abstract: The present disclosure provides icIEF sample matrices that enable icIEF analysis of PEGylated proteins in their real conjugated states. The sample matrices of the present disclosure can include glycine, which enables the separation of co-migrated PEGylated protein charge variants. The sample matrices can also include taurine, whichfurther improves icIEF assay by depleting matrix induced baseline interferences. Accordingly, a sample matrix of the present disclosure including a combination of glycine and taurine enables icIEF separation of acidic and basic species from the main peak for PEGylated proteins, allowing the identification/separation, characterization and quantification of discrete PEGylated protein species. By using the sample matrices of the present disclosure to characterize PEGylated proteins by icIEF, repeatability, linearity, accuracy, sample stability, and method robustness are achieved.Type: ApplicationFiled: January 27, 2021Publication date: March 9, 2023Applicant: Bristol-Myers Squibb CompanyInventors: Xin ZHANG, Letha CHEMMALIL, Julia DING, Zhengjian LI
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Publication number: 20230050031Abstract: In certain embodiments, the present invention provides novel antibody purification methods and systems using a potentially simple and cost-efficient means. In some embodiments, customized Z-33 derived from Staphylococcus aureus Protein A is used to construct immuno-amphiphile molecules which can assemble into immunofibers in aqueous solution with bioactive epitopes on the surface and have IgG binding ability.Type: ApplicationFiled: June 7, 2022Publication date: February 16, 2023Inventors: Honggang Cui, Yi Li, Xuankuo Xu, Lye Lin Lock, Zhengjian Li
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Publication number: 20230025648Abstract: This disclosure provides a novel label-free N-glycan analysis method to detect and quantify N-glycans and N-linked glycosylation profiles without using a label, such as a fluorescent label. This method allows for reduced sample preparation and chromatographic separation times, and can be used for product batch release.Type: ApplicationFiled: November 23, 2020Publication date: January 26, 2023Applicant: Bristol-Myers Squibb CompanyInventors: Letha CHEMMALIL, Julia DING, Zhengjian LI
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Patent number: 11542337Abstract: In certain embodiments, the disclosure provides an IgG4 antibody comprising a heavy chain and a light chain, wherein the heavy chain comprises: (a) a modified IgG4 CH1 region having a substitution of the lysine residue at position 196; or (b) a modified IgG4 hinge region having a substitution of the serine residue at position 217, the glycine residue at position 220, the proline residue at position 224 or the proline residue at position 225. Preferably, the IgG4 antibody further comprises a substitution of the serine residue at position 228 in the heavy chain hinge region.Type: GrantFiled: December 22, 2017Date of Patent: January 3, 2023Assignee: BRISTOL MYERS SQUIBB COMPANYInventors: Zhiqiang Chen, Yueming Qian, Xuankuo Xu, Chao Huang, Zhijun Tan, Zhengjian Li
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Publication number: 20220315887Abstract: In certain embodiments, this disclosure provides a method of increasing production of a recombinant polypeptide of interest, comprising: a) seeding mammalian cells in a fed-batch production bioreactor at a viable cell density of at least 5106 viable cells/ml; and b) culturing the cells under optimized culture conditions to produce the recombinant polypeptide of interest at high titer.Type: ApplicationFiled: July 30, 2020Publication date: October 6, 2022Applicant: Bristol-Myers Squibb CompanyInventors: Jianlin XU, Qin HE, Mengmeng XU, Matthew Stephen REHMANN, Charles Anthony HILL, Christopher Louis OLIVEIRA, Michael Christopher BORYS, Zhengjian LI, Shun ZHENG
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Patent number: 11359005Abstract: In certain embodiments, the present invention provides novel antibody purification methods and systems using a potentially simple and cost-efficient means. In some embodiments, customized Z-33 derived from Staphylococcus aureus Protein A is used to construct immuno-amphiphile molecules which can assemble into immunofibers in aqueous solution with bioactive epitopes on the surface and have IgG binding ability.Type: GrantFiled: March 28, 2018Date of Patent: June 14, 2022Assignees: THE JOHNS HOPKINS UNIVERSITY, BRISTOL-MYERS SQUIBB COMPANYInventors: Honggang Cui, Yi Li, Xuankuo Xu, Lye Lin Lock, Zhengjian Li
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Publication number: 20220162260Abstract: In certain embodiments, the invention provides a method of purifying a protein of interest from a mixture which comprises the protein of interest and one or more contaminants, comprising: (a) contacting the mixture with a dextran polymer under conditions suitable for the dextran polymer to bind to one or more contaminants, thereby to form a contaminant precipitate; (b) separating the contaminant precipitate from the mixture to form a solution, thereby purifying the protein of interest.Type: ApplicationFiled: February 8, 2022Publication date: May 26, 2022Inventors: Zhijun Tan, Nripen Singh, Mi Jin, Chao Huang, Richard P. Martel, JR., Angela T. Lewandowski, Zhengjian Li
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Publication number: 20220135619Abstract: The disclosure provides a method of separating a protein product, e.g., from a contaminant in a mixture, comprising contacting the mixture with a polishing chromatography matrix. In some embodiments, the polishing chromatography matrix is used together with a retained gradient. In certain embodiments, the retained gradient comprises a pH gradient. In certain embodiments, the mixture comprises a monoclonal antibody product of a prior protein A chromatography.Type: ApplicationFiled: February 24, 2020Publication date: May 5, 2022Applicant: Bristol-Myers Squibb CompanyInventors: Douglas D. FREY, Yang LIU, Sevda DELDARI, Ryan Keith SWANSON, Chittoor R. NARAHARI, Ronald Charles BATES, Sanchayita GHOSE, Zhengjian LI
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Publication number: 20220042954Abstract: In certain embodiments, the present invention provides a method of measuring the level of hydrophobicity of a chromatographic resin. In certain embodiments, the present invention provides a method of selecting a chromatographic resin condition for purifying a protein of interest from a mixture, wherein the protein of interest has low or no aggregation formation during chromatography. In certain embodiments, the present invention provides a method of selecting a chromatographic resin from a plurality of chromatographic resins for purifying a protein of interest from a mixture, wherein the protein of interest has low or no aggregation formation during chromatography.Type: ApplicationFiled: March 27, 2020Publication date: February 10, 2022Inventors: Chao HUANG, Joseph James PERRY, Xuankuo XU, Sanchayita GHOSE, Zhengjian LI, Weixin JIN
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Publication number: 20220017570Abstract: This disclosure provides a novel method of purifying PEGylated proteins using ion exchange chromatography by loading PEGylated protein having a high concentration, e.g., at least 6 grams/liter on an ion exchange chromatography matrix, and collecting the PEGylated protein.Type: ApplicationFiled: November 4, 2019Publication date: January 20, 2022Inventors: Deqiang YU, John PAGANO, Hasin FEROZ, Yuanli SONG, Sanchayita GHOSE, Zhengjian LI
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Publication number: 20210300964Abstract: Methods for the production of high purity recombinant protein such as monoclonal antibodies (mAb) using disulfide bond re-oxidation are provided. In particular, the present disclosure provides methods for converting partial molecules (e.g., antibody fragments) to full molecules (e.g., full antibodies) comprising admixing a starting solution comprising the partial molecules with a redox buffer comprising a redox pair which comprises at least one thiol reducing agent (e.g., cysteine) and at least one thiol oxidizing agent (e.g., cystine), wherein the redox buffer re-oxidizes the partial molecules to full molecules. The disclosed methods can be used, e.g., to prevent or mitigate the formation of partial molecules during protein purification, or to reprocess or rescue a solution comprising partial molecules (e.g., a partially degraded pharmaceutical formulation).Type: ApplicationFiled: August 15, 2019Publication date: September 30, 2021Inventors: Zhijun Tan, Vivekh Ehamparanathan, Shing Fung Lam, Cheng Du, Derek Choy, Angela T Lewandowski, Sanchayita Ghose, Zhengjian Li, Laurel Hoffman
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Publication number: 20210246161Abstract: In some embodiments, the present invention provides a method of purifying a protein of interest with a reduced level of aggregation formation in cation exchange (CEX) chromatography, comprising: (a) providing a mixture comprising the protein of interest and one or more contaminants; (b) loading the mixture onto a CEX resin coupled with arginine; and (c) eluting the protein of interest from the resin, thereby purifying the protein of interest with a reduced level of aggregation formation in CEX chromatography.Type: ApplicationFiled: February 10, 2021Publication date: August 12, 2021Inventors: Zhengjian Li, Xuankuo Xu, Chao Huang, Zhiqiang Chen