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1. 发明授权

US12139816B2 Protease-resistant systems for polypeptide display and methods of making and using thereof 有权
公开(公告)号：US12139816B2
公开(公告)日：2024-11-12
申请号：US17521042
申请日：2021-11-08
申请人： CytomX Therapeutics, Inc.
发明人： Sherry Lynn La Porte , Stephen James Moore , James William West
IPC分类号： C40B30/06 , C07K14/00 , C07K14/705 , C07K16/18 , C07K16/28 , C12N15/10 , C12Q1/37 , G01N33/68 , C40B40/02
CPC分类号： C40B30/06 , C07K14/001 , C07K14/705 , C07K16/18 , C07K16/2809 , C07K16/2866 , C12N15/1037 , C12N15/1044 , C12Q1/37 , G01N33/6845 , C07K2317/622 , C07K2319/02 , C07K2319/03 , C07K2319/21 , C40B40/02
摘要： The present invention generally relates to bacterial polypeptide display systems, libraries using these bacterial display systems, and methods of making and using these systems, including methods for improved display of polypeptides on the extracellular surface of bacteria using circularly permuted transmembrane bacterial polypeptides that have been modified to increase resistance to protease degradation and to enhance polypeptide display characteristics.

2. 发明公开

US20240325460A1 MOLECULAR BACTERIOTHERAPY TO CONTROL SKIN ENZYMATIC ACTIVITY 审中-公开
公开(公告)号：US20240325460A1
公开(公告)日：2024-10-03
申请号：US18494552
申请日：2023-10-25
申请人： The Regents of the University of California
发明人： Richard L. Gallo , Michael Williams
IPC分类号： A61K35/741 , A61K9/00 , A61K9/06 , A61K38/08 , A61P17/00 , C12Q1/37
CPC分类号： A61K35/741 , A61K9/0014 , A61K9/06 , A61K38/08 , A61P17/00 , C12Q1/37 , G01N2333/96425 , G01N2800/202
摘要： The disclosure relates to composition and methods to treat dermatological diseases and disorders and to composition that modulate skin barrier permeability.

3. 发明公开

US20240302276A1 POLYPEPTIDE SEQUENCING AND FINGERPRINTING 审中-公开
公开(公告)号：US20240302276A1
公开(公告)日：2024-09-12
申请号：US18569128
申请日：2022-06-02
申请人： Quantapore, Inc.
发明人： Milya DAVLIEVA , Martin HUBER
IPC分类号： G01N21/64 , C12Q1/37 , G01N33/487 , G01N33/68
CPC分类号： G01N21/6408 , C12Q1/37 , G01N21/6428 , G01N33/48721 , G01N33/6818 , G01N2021/6419 , G01N2021/6421 , G01N2021/6441
摘要： In some aspects, the invention comprises a method for determining an amino acid sequence or fingerprint of a polypeptide. In some embodiments, the method comprises providing a solid state substrate comprising a cis side and a trans side, the substrate comprising a reaction well that defines a reaction volume and comprises (i) a proximal throughhole extending between the cis side and the trans side of the substrate, (ii) one or more side walls, and (iii) a distal opening. The solid state substrate further comprises an opaque metal layer that substantially blocks excitation light from penetrating into the reaction volume and from penetrating to the cis side of the substrate. Also provided is a carrier particle comprising a fluorescently labeled polypeptide strand that is attached to the carrier particle. The fluorescently labeled polypeptide strand comprises (i) a proximal end that is attached to the carrier particle, (ii) a distal end that is cleavable by an exopeptidase, and (iii) at least one fluorescently labeled amino acid comprising a fluorescent label. The carrier particle is located on the cis side of the substrate, but does not pass through the throughhole, such that the attached fluorescently labeled polypeptide strand protrudes through the throughhole so that the distal end of the fluorescently labeled strand is in the reaction volume. The trans side of the substrate is illuminated with excitation light to create a fluorescence excitation zone adjacent to the distal opening of the reaction well. While the substrate is illuminated, the fluorescently labeled polypeptide strand is reacted with an exopeptidase so that amino acids are released serially from the distal end of the stand and diffuse through the fluorescence excitation zone, so that fluorescently labeled amino acids in the excitation zone emit fluorescent signals. The fluorescent signals are detected as a function of time, whereby an amino acid sequence is determined from the time order of fluorescent signals detected from the released fluorescently labeled amino acids.

4. 发明公开

US20240272160A1 IMMUNO-BASED RETARGETED ENDOPEPTIDASE ACTIVITY ASSAYS 审中-公开
公开(公告)号：US20240272160A1
公开(公告)日：2024-08-15
申请号：US18392925
申请日：2023-12-21
申请人： Allergan, Inc.
发明人： Joanne Wang , Hong Zhu , Dianne D. Hodges , Ester Fermandez-Salas
IPC分类号： G01N33/573 , C07K16/18 , C12N9/52 , C12Q1/37 , G01N33/50 , G01N33/53
CPC分类号： G01N33/573 , C07K16/18 , C12N9/52 , C12Q1/37 , C12Y304/24069 , G01N33/5014 , G01N33/5035 , G01N33/53 , C07K2317/34 , C07K2317/56 , C07K2317/92 , G01N2333/33 , G01N2333/47 , G01N2333/952 , G01N2333/96425
摘要： The present specification discloses a retargeted endopeptidase pharmaceutical wherein the activity has been determined by the methods disclosed.

5. 发明授权

US12060591B2 Tau protease compositions and methods of use 有权
公开(公告)号：US12060591B2
公开(公告)日：2024-08-13
申请号：US16822906
申请日：2020-03-18
申请人： Oligomerix, Inc.
发明人： James G. Moe , Eliot J. Davidowitz , Patricia Lopez
IPC分类号： C12N9/64 , A61K38/00 , A61K38/48 , A61K39/395 , C07K16/40 , C12Q1/37 , G01N33/573 , G01N33/68
CPC分类号： C12N9/6424 , A61K38/482 , A61K39/3955 , C07K16/40 , C12Q1/37 , G01N33/573 , G01N33/6896 , A61K38/00 , G01N2800/2821
摘要： Disclosed are mammalian tau proteases, as well as proteolytically-active fragments, variants, and mutants thereof. Also disclosed are polynucleotides and recombinant expression vectors that encode these polypeptides, as well as methods for producing such proteins in selected recombinant host cells, and for using the compositions in a variety of diagnostic and analytical assays.

6. 发明公开

US20240240228A1 BRET-BASED CORONAVIRUS MPRO PROTEASE SENSOR AND USES THEREOF 审中-公开
公开(公告)号：US20240240228A1
公开(公告)日：2024-07-18
申请号：US18562772
申请日：2022-05-20
申请人： Qatar Foundation for Education, Science and Community Development
发明人： Anupriya M. Geethakumari , Kabir Hassan Biswas
IPC分类号： C12Q1/37 , G01N21/64
CPC分类号： C12Q1/37 , G01N21/6428 , G01N21/6458
摘要： The SARS-CoV-2 main protease, MPRO, is critical for its replication and is an appealing target for designing anti-SARS-CoV-2 agents. In this regard, a number of assays have been developed based on its cleavage sequence preferences to monitor its activity. These include the usage of Fluorescence Resonance Energy Transfer (FRET)-based substrates in vitro and a FlipGFP reporter, one which fluoresces after MPRO-mediated cleavage, in live cells. Here, a pair of genetically encoded, Bioluminescence Resonance Energy Transfer (BRET)-based sensors have been engineered for detecting SARS-CoV-2 MPRO proteolytic activity in living host cells. The sensors were generated by sandwiching MPRO N-terminal autocleavage sites, either AVLQSGFR (short) or KTSAVLQSGFRKME (long), in between the mNeonGreen and nanoLuc proteins. Co-expression of the sensor with the MPRO in live cells resulted in its cleavage in a dose-dependent manner while mutation of the critical C145 residue (C145A) in MPRO completely abrogated the sensor cleavage. A temporal activity of MPRO in live cells and its inhibition was shown using the well-characterized pharmacological agent GC376. The sensor developed here finds direct utility in studies related to drug discovery targeting the SARS-CoV-2 MPRO and functional genomics application to determine the effect of sequence variation in MPRO Importantly, the BRET-based sensors displayed increased sensitivities and specificities as compared to the recently developed FlipGFP-based MPRO sensor. Additionally, the sensors recapitulated the inhibition of MPRO by the well-characterized pharmacological agent GC376. Further, in vitro assays with the BRET-based MPRO sensors revealed a molecular crowding-mediated increase in the rate of MPRO activity and a decrease in the inhibitory potential of GC376. The sensor developed here finds direct utility in studies related to drug discovery targeting the SARS-CoV-2 MPRO and functional genomics application to determine the effect of sequence variation in MPRO.

7. 发明公开

US20240238459A1 Granzyme-Activatable Membrane-Interacting Peptides and Methods of Use 审中-公开
公开(公告)号：US20240238459A1
公开(公告)日：2024-07-18
申请号：US18563182
申请日：2022-06-30
申请人： The Regents of the University of California
发明人： Charles S. Craik , Conner Bardine , Michael Evans
IPC分类号： A61K51/08 , A61K47/64 , A61K47/65 , A61K49/00 , C12Q1/37
CPC分类号： A61K51/088 , A61K47/64 , A61K47/65 , A61K49/0032 , A61K49/0056 , C12Q1/37
摘要： The present disclosure provides granzyme-activatable and detectable membrane-interacting peptides that, following activation, can interact with phospholipid bilayers, such as cell membranes. The present disclosure also provides methods of use of such peptides, as well as compositions comprising such peptides. The peptides of the present disclosure are of the general structure X1a-A-X2—Z—X1b, where A is a membrane-interacting peptide region having a plurality of nonpolar hydrophobic amino acid residues that, following separation from portions Z, is capable of interaction with a phospholipid bilayer; Z is an inhibitory peptide region that can inhibit the activity of portion A; X2 is a granzyme-cleavable linker that can be cleaved to release cleavage products from the compound; and X1a and X1b are optionally-present chemical handles that facilitate conjugation of various cargo moieties to the compound.

8. 发明公开

US20240230678A1 P53 POST-TRANSLATIONAL MODIFICATIONS AS MARKERS IN THE DIAGNOSIS AND PROGNOSIS OF A NEURODEGENERATIVE DISEASE 审中-公开
公开(公告)号：US20240230678A1
公开(公告)日：2024-07-11
申请号：US18007088
申请日：2021-07-27
申请人： DIADEM S.p.A.
发明人： Simona Piccirella , Daniela Letizia Uberti
IPC分类号： G01N33/68 , C12Q1/37
CPC分类号： G01N33/6896 , C12Q1/37 , G01N33/6848 , G01N33/6854 , G01N2333/4748 , G01N2333/976 , G01N2440/00 , G01N2800/2821 , G01N2800/52
摘要： The present invention refers to p53 sequence and post translational modifications (PTMs) and to their use as biomarkers in the diagnosis of neurodegenerative disease and cognitive decline and/or in the prognosis of Alzheimer's disease at different stages and/or of neurodegenerative disease in a biological sample. The invention also provides for a 1) diagnostic method based on a highly accurate mass spectrometry analysis for the diagnosis of neurodegenerative disease, including Mild Cognitive Impairment (MCI), Alzheimer's disease (AD), fronto-temporal dementia (FTD), Lewi's Body (LB), and vascular dementia (VD) in a subject, by evaluating the PTMs to the said p53 linear sequence protein and possible cut of its full sequence specifically in human plasma of patients; and 2) prognosis of AD in CU and MCI patients.

9. 发明授权

US11959124B2 Methods and systems for determining ADAMTS13 enzyme activity 有权
公开(公告)号：US11959124B2
公开(公告)日：2024-04-16
申请号：US17088778
申请日：2020-11-04
申请人： Laboratory Corporation of America Holdings
发明人： Russell Philip Grant , Christopher Michael Shuford , Meghan Norris Bradley
IPC分类号： C12Q1/37 , C12Q1/00 , G01N33/68
CPC分类号： C12Q1/37 , C12Q1/005 , G01N33/6851 , G01N2333/96486 , G01N2560/00 , G01N2800/226
摘要： Disclosed are methods and systems for the analysis activity of enzyme disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) in a sample. The methods and systems disclosed herein can be useful for diagnosis of thrombotic thrombocytopenic purpura in a patient.

10. 发明授权

US11952612B2 Protease sensor molecules 有权
公开(公告)号：US11952612B2
公开(公告)日：2024-04-09
申请号：US16349237
申请日：2017-11-13
申请人： Commonwealth Scientific and Industrial Research Organisation
发明人： Helen Dacres , Stephen Charles Trowell
IPC分类号： C12Q1/37 , C12Q1/06 , G01N21/76 , G01N33/52
CPC分类号： C12Q1/37 , C12Q1/06 , G01N21/76 , G01N33/52 , G01N2333/21
摘要： The present invention relates to sensors and methods for detecting bacterial proteases in a sample. In particular, the present invention relates to sensors and methods for detecting Pseudomonas spp. protease activity in a sample. The sensors and methods may be used to detect or predict spoilage of a dairy product. The invention also relates to methods for preparing samples for protease assays.

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