Harvard College

Merck Patent Gmbh

Vertex Pharmaceuticals, Inc.

Valerion Therapeutics, LLC

Other

Merck Patent Gesellschaft MIT Beschrankter Haftung

Ginkgo Bioworks, Inc.

Dana-farber-cancer Institute Inc.

Jeffrey Charles Way

Donald Elliot Ingber

Michael Super

Stephen D Gillies

Mark J Cartwright

Anita Anne Hamilton

Alexander L Watters

Martin M Rottman

Julia B Berthet

Dinah R Super

Eric Steven Furfine

Dustin D Armstrong

Avram Lev Robinson-Mosher

Matthew John Traylor

Christopher D Thanos

Edwin L Madison

Jonathan W Kotula

Mikhail Popkov

Vanessa Soros

Pamela Ann Silver

Scott Jordan Kerns

Kimberly Tipton

Matthew Baker

Francis Joseph Carr

Kin-Ming Lo

Stephen Williams

Jean Zhao

Yuan Liu

Graham Carter

Thomas M Roberts

John Watkins

Marian Hanlon

Grant E Blouse

Tom Knudsen

Jones Tim

Lev Shaket

Jan Kristian Jensen

Emil Oldenburg

Christine René Schar

Agnieszka Jendroszek

Arzu Sandikci

Jim Mcguire

Shyam Rajan Iyer

Natacha Le Moan

Brajesh Kumar

Joseph H Davis

Martin Rottman

Provided are nucleic acid molecules, including vectors and plasmids, encoding modified u-PA polypeptides and fusion proteins containing the modified u-PA polypeptides. The u-PA polypeptides are modified to have altered activity and/or specificity so that they cleave a complement protein, such as complement protein C3, to thereby inhibit complement activation. The nucleic acids and encoded modified u-PA polypeptides and fusion proteins that inhibit complement activation can be used for treatment of diseases and conditions that are mediated by complement activation, or in which complement activation plays a role. These disorders include ischemic and reperfusion disorders, including myocardial infarction and stroke, sepsis, autoimmune diseases, diabetic retinopathies, age-related macular degeneration, transplanted organ rejection, inflammatory diseases and diseases with an inflammatory component.

Modified urokinase-type plasminogen activator polypeptides and methods of use

Provided herein are Complement Factor I (CFI) variants that exhibit at least one improved characteristic relative to a wild type CFI. CFI variants of the disclosure can exhibit tunable specificity and activity. Also included are CFI-containing fusion constructs comprising at least one domain of CFI, for example, wild type full length CFI fused to human serum albumin. Also included are methods of making and using such CFI variants and fusion constructs. The CFI variants and fusion constructs provided herein may be useful for treating a disease or condition associated with dysregulation of the complement system or a deficiency of CFI.

Complement factor I-related compositions and methods

Described herein are engineered microbe-targeting or microbe-binding molecules, kits comprising the same and uses thereof. Some particular embodiments of the microbe-targeting or microbe-binding molecules comprise a carbohydrate recognition domain of mannose-binding lectin, or a fragment thereof, linked to a portion of a Fc region. In some embodiments, the microbe-targeting molecules or microbe-binding molecules can be conjugated to a substrate, e.g., a magnetic microbead, forming a microbe-targeting substrate (e.g., a microbe-targeting magnetic microbead). Such microbe-targeting molecules and/or substrates and the kits comprising the same can bind and/or capture of a microbe and/or microbial matter thereof, and can thus be used in various applications, e.g., diagnosis and/or treatment of an infection caused by microbes such as sepsis in a subject or any environmental surface. Microbe-targeting molecules and/or substrates can be regenerated after use by washing with a low pH buffer or buffer in which calcium is insoluble.

Engineered microbe-targeting molecules and uses thereof

Provided are u-PA polypeptides and fusion proteins containing the u-PA polypeptides. The u-PA polypeptides are modified to have altered activity and/or specificity so that they cleave a complement protein, such as complement protein C3, to thereby inhibit complement activation. The modified u-PA polypeptides and fusion proteins that inhibit complement activation can be used for treatment of diseases and conditions that are mediated by complement activation, or in which complement activation plays a role. These disorders include ischemic and reperfusion disorders, including myocardial infarction and stroke, sepsis, autoimmune diseases, diabetic retinopathies, age-related macular degeneration, transplanted organ rejection, inflammatory diseases and diseases with an inflammatory component.

The present invention provides for engineered molecular opsonins that may be used to bind biological pathogens or identify subclasses or specific pathogen species for use in devices and systems for treatment and diagnosis of patients with infectious diseases, blood-borne infections or sepsis. An aspect of the invention provides for mannose-binding lectin (MBL), which is an abundant natural serum protein that is part of the innate immune system. The ability of this protein lectin to bind to surface molecules on virtually all classes of biopathogens (viruses, bacteria, fungi, protozoans) make engineered forms of MBL extremely useful in diagnosing and treating infectious diseases and sepsis.

Engineered opsonin for pathogen detection and treatment

Aspects of the disclosure provide fusion proteins that bind cells expressing one or more target molecules including, for example, one or more cell surface multisubunit signaling receptors (e.g., EGFRvIII-expressing cells that also express interferon receptors) and that induce anti-proliferative effects, and related compositions and methods for the treatment of cancer.

Fusion proteins for treating cancer and related methods

The disclosure relates to genetic engineered bacteria having a genetic memory circuit, compositions thereof, formulations thereof, methods of analyses and method of treatment of conditions related to the gastrointestinal tract including the mouth and the stomach.

Engineered genetic enteric sensor bacteria and uses thereof

The present disclosure provides antibodies and antigen-binding fragments capable of penetrating cells via an ENT transporter, such as humanized antibodies. The disclosure also provides conjugates comprising the antibodies or antigen-binding fragments and a heterologous agent. The disclosure further provides methods for making and using the antibodies, antigen-binding fragments and conjugates, including humanized antibodies.

Internalizing moieties

The invention features methods and compositions relating to cells that have been engineered to reduce or eliminate proteins having enzymatic activity that interfere with the expression of a metabolic product.

Methods and molecules for yield improvement involving metabolic engineering

Growing community of inventors

Cambridge, MA, United States of America

Jeffrey Charles Way