Abstract: The present disclosure includes engineering methods and polypeptide libraries that are useful for introducing non-native binding sites into polypeptides. Also provided herein are polypeptides that bind to a CD98hc or transferrin receptor (TfR) protein, methods of generating such polypeptides, and methods of using the polypeptides to target a composition across the blood-brain barrier or to a CD98hc-expressing or TfR-expressing cell.
Type:
Application
Filed:
December 16, 2022
Publication date:
May 8, 2025
Applicant:
DENALI THERAPEUTICS INC.
Inventors:
Padma Akkapeddi, Gerald Maxwell Cherf, Kylie S. Chew, Mark S. Dennis, Zhenyu Gu, Mihalis S. Kariolis, Hai L. Tran, Robert C. Wells, Joy Yu Zuchero
Abstract: Provided herein are proteins, which are capable of being transported across the blood-brain barrier (BBB) and comprise an alpha-L-iduronidase (IDUA) enzyme-Fc fusion polypeptide. Certain embodiments also provide methods of using such proteins to treat MPS I.
Type:
Application
Filed:
December 16, 2022
Publication date:
May 1, 2025
Applicant:
DENALI THERAPEUTICS INC.
Inventors:
Gowrisudha ADUSUMILLI, Oliver Brayer DAVIS, Mihalis S. KARIOLIS, Cathal S. MAHON, Shrishti TYAGI, Kensuke YAMANOKUCHI
Abstract: In one aspect, antibodies that specifically bind to a human triggering receptor expressed on myeloid cells 2 (TREM2) protein are provided. In some embodiments, the antibody decreases levels of soluble TREM2 (sTREM2). In some embodiments, the antibody enhances TREM2 activity.
Type:
Grant
Filed:
August 16, 2021
Date of Patent:
March 4, 2025
Assignee:
Denali Therapeutics Inc.
Inventors:
Mark S. Dennis, Sherie Duncan, Kathleen Lisaingo, Kathryn M. Monroe, Joshua I. Park, Rachel Prorok, Ju Shi, Ankita Srivastava, Bettina Van Lengerich, Riley Walsh
Abstract: Certain embodiments provide a method of providing added peripheral IDS activity to a subject with Hunter syndrome, comprising administering to the subject a therapeutically effective dose of a pharmaceutical composition comprising a protein comprising an IDS amino acid sequence and a TfR binding domain. The added peripheral IDS activity can be measured by comparing levels of keratan sulfate (KS) in the subject after administration of the pharmaceutical composition relative to a baseline level. Certain embodiments also provide methods of providing a clinical benefit to a subject with Hunter syndrome and improving treatment in a patient having non-neuronopathic Hunter syndrome, as well as methods and treatment regimens for resolving infusion related reactions (IRRs).
Type:
Application
Filed:
July 22, 2022
Publication date:
January 16, 2025
Applicant:
DENALI THERAPEUTICS INC.
Inventors:
Annie ARGUELLO, Akhil BHALLA, Jeffrey Mark HARRIS, Matthew D. TROYER
Abstract: The present disclosure relates generally to compounds and compositions, intermediates, processes for their preparation, and their use as kinase inhibitors.
Type:
Application
Filed:
September 18, 2024
Publication date:
January 9, 2025
Applicant:
Denali Therapeutics Inc.
Inventors:
Javier de Vicente Fidalgo, Anthony A. Estrada, Jianwen A. Feng, Brian Fox, Cinzia Maria Francini, Christopher R.H. Hale, Cheng Hu, Colin Philip Leslie, Maksim Osipov, Elena Serra, Zachary K. Sweeney, Arun Thottumkara
Abstract: Methods and systems described herein may allow for the classification of microglial morphology at single cell resolution. Microglial cell states may be determined, and a biological sample from which the microglial cells are obtained may be classified based on the microglial cell states. Classifying microglial cells may involving segmenting microglia cells into soma and processes in immunofluorescence microscopy images. Additionally, a feature bank may be generated. Values of the features in the feature bank may be measured for an image. Cells may be clustered using the values of the features in the feature bank. The cells in a cluster may be compared to a reference cell with a known state and having known morphological properties. The cluster in the cell may then be assigned the same state as a reference cell. The amount of cells having the state may then be used to determine properties of the biological sample.
Abstract: Provided herein are polypeptides that bind to a transferrin receptor, methods of generating such polypeptides, and methods of using the polypeptides to target a composition to a transferrin receptor-expressing cell.
Type:
Grant
Filed:
April 23, 2024
Date of Patent:
December 10, 2024
Assignee:
Denali Therapeutics Inc.
Inventors:
Xiaocheng Chen, Mark S. Dennis, Mihalis Kariolis, Adam P. Silverman, Ankita Srivastava, Ryan J. Watts, Robert C. Wells, Joy Yu Zuchero
Abstract: Described herein are crystalline forms of (S)-5-benzyl-N-(5-methyl-4-oxo-2,3,4,5-tetrahydropyrido [3,2-b][1,4]oxazepin-3-yl)-4H-1,2,4-triazole-3-carboxamide, the process of preparing the forms, and pharmaceutical compositions methods of use thereof.
Abstract: The present disclosure relates generally to eukaryotic initiation factor 2B modulators, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or prodrug thereof, and methods of making and using thereof.
Type:
Grant
Filed:
August 31, 2018
Date of Patent:
November 12, 2024
Assignee:
Denali Therapeutics Inc.
Inventors:
Robert A. Craig, II, Javier de Vicente Fidalgo, Anthony A. Estrada, Jianwen A. Feng, Katrina W. Lexa, Maksim Osipov, Zachary K. Sweeney
Abstract: The present disclosure relates generally to compounds and compositions, intermediates, processes for their preparation, and their use as kinase inhibitors.
Type:
Grant
Filed:
October 26, 2021
Date of Patent:
October 29, 2024
Assignee:
DENALI THERAPEUTICS INC.
Inventors:
Javier de Vicente Fidalgo, Anthony A. Estrada, Jianwen A. Feng, Brian Fox, Cinzia Maria Francini, Christopher R. H. Hale, Cheng Hu, Colin Philip Leslie, Maksim Osipov, Elena Serra, Zachary K. Sweeney, Arun Thottumkara
Abstract: Described herein are solid forms of 4-(3,3-difluoro-2,2-dimethyl-propanoyl)-3,5-dihydro-2H-pyrido[3,4-f][1,4]oxazepine-9-carbonitrile, the process of preparing the forms, pharmaceutical compositions comprising same, and methods of use thereof.
Type:
Application
Filed:
February 20, 2024
Publication date:
September 26, 2024
Applicant:
Denali Therapeutics Inc.
Inventors:
Javier de Vicente Fidalgo, Brian M. Fox, Christopher R.H. Hale
Abstract: The present disclosure relates generally to eukaryotic initiation factor 2B modulators, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or prodrug thereof, and methods of making and using thereof.
Type:
Grant
Filed:
February 12, 2020
Date of Patent:
September 17, 2024
Assignee:
Denali Therapeutics Inc.
Inventors:
Robert A. Craig, II, Javier de Vicente Fidalgo, Jianwen A. Feng, Maksim Osipov, Arun Thottumkara
Abstract: Provided herein are polypeptides that bind to a transferrin receptor, methods of generating such polypeptides, and methods of using the polypeptides to target a composition to a transferrin receptor-expressing cell.
Type:
Application
Filed:
February 7, 2024
Publication date:
August 15, 2024
Applicant:
Denali Therapeutics Inc.
Inventors:
Xiaocheng Chen, Mark S. Dennis, Mihalis Kariolis, Adam P. Silverman, Ankita Srivastava, Robert C. Wells, Joy Yu Zuchero, Ryan J. Watts
Abstract: Provided herein are polypeptides that bind to a transferrin receptor, methods of generating such polypeptides, and methods of using the polypeptides to target a composition to a transferrin receptor-expressing cell.
Type:
Application
Filed:
April 23, 2024
Publication date:
August 15, 2024
Applicant:
Denali Therapeutics Inc.
Inventors:
Xiaocheng Chen, Mark S. Dennis, Mihalis Kariolis, Adam P. Silverman, Ankita Srivastava, Ryan J. Watts, Robert C. Wells, Joy Yu Zuchero
Abstract: Described herein are crystalline forms of (S)-5-benzyl-N-(5-methyl-4-oxo-2,3,4,5-tetrahydropyrido [3,2-b][1,4]oxazepin-3-yl)-4H-1,2,4-triazole-3-carboxamide, the process of preparing the forms, and pharmaceutical compositions methods of use thereof.
Abstract: Certain embodiments provide a fusion protein comprising an iduronate 2-sulfatase (IDS) amino acid sequence, an IDS variant amino acid sequence, or a catalytically active fragment thereof; and an anti-transferrin receptor (TfR) antibody as described herein, as well as methods of use thereof.
Type:
Application
Filed:
February 11, 2022
Publication date:
May 9, 2024
Applicant:
DENALI THERAPEUTICS INC.
Inventors:
Annie ARGUELLO, Tina GIESE, Gunasekaran KANNAN, Mihalis S. KARIOLIS, Cathal S. MAHON, Junhua WANG
Abstract: Provided herein are proteins, which are capable of being transported across the blood-brain barrier (BBB) and comprise sulfoglucosamine sulfohydrolase (SGSH) enzyme-Fc fusion polypeptides. Certain embodiments also provide methods of using such proteins to treat Sanfilippo syndrome A.
Type:
Application
Filed:
January 12, 2024
Publication date:
May 9, 2024
Applicant:
DENALI THERAPEUTICS INC.
Inventors:
Tina GIESE, Gunasekaran KANNAN, Mihalis S. KARIOLIS, Cathal S. MAHON
Abstract: The present disclosure relates generally to compounds and compositions, and their use as kinase inhibitors.
Type:
Application
Filed:
August 10, 2023
Publication date:
May 9, 2024
Applicant:
Denali Therapeutics Inc.
Inventors:
Anthony A. Estrada, Jianwen A. Feng, Brian Fox, Colin Phillip Leslie, Joseph P. Lyssikatos, Alfonso Pozzan, Zachary K. Sweeney, Javier de Vicente Fidalgo
Abstract: Provided herein are polypeptides that bind to a transferrin receptor, methods of generating such polypeptides, and methods of using the polypeptides to target a composition to a transferrin receptor-expressing cell.
Type:
Application
Filed:
January 9, 2024
Publication date:
May 2, 2024
Applicant:
Denali Therapeutics Inc.
Inventors:
Xiaocheng Chen, Mark S. Dennis, Mihalis Kariolis, Adam P. Silverman, Ankita Srivastava, Ryan J. Watts, Robert C. Wells, Joy Yu Zuchero