Fusion proteins for the diagnosis, prophylaxis and treatment of infectious diseases
Inventors
Ahmed, Mahiuddin • Sequeira, Sonia
Assignees
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Publication Number
US-11197910-B1
Publication Date
2021-12-14
Expiration Date
Abstract
The present invention relates to the use of phosphotidylserine or pathogenic sugar targeted therapeutics for the management and treatment of microbial infections, including Zika, Dengue, West Nile, Ebola, H1N1, enteroviruses, Leishmaniasis, Malaria and Coronaviruses SARS-COV.
Core Innovation
The invention relates to a phosphatidylserine (PS)-binding fusion construct platform that combines an Ig-Fc domain with a PS-binding peptide, protein, or antibody fragment selected from TIM-1 and fragments thereof. The construct further includes a peptide or protein that binds to and/or recognizes a PAMP expressed by a microbe, wherein the PAMP-binding component is selected from DC-SIGN and fragments thereof.
The problem being addressed is the management of infections across multiple pathogen classes, using a fusion construct platform that can recognize a host-related PS signal and microbe-associated PAMP signals via PS-binding and DC-SIGN PAMP-recognition elements. The described platform is positioned for pan-pathogen management by enabling PS recognition through TIM-1 and PAMP recognition through DC-SIGN within a single fusion architecture.
The described fusion architecture is based on an Ig-Fc scaffold that supports engineered effector-function properties and variant embodiments. The platform is disclosed with extensive fusion designs, including Ig-Fc configurations and heterodimerization/hinge-related engineering, as well as optional payload coupling, and effectors associated with ADCC, ADCP, and CDC, alongside variants that include additional features such as T-cell engager via anti-CD3 scFv and IgM effector-function heterodimers for CDC.
Claims Coverage
The independent claim covers a fusion construct platform defined by two functional binding modules, TIM-1 PS-binding and DC-SIGN PAMP-recognition, fused to an Ig-Fc domain with first-chain and second-chain sequence selections specified by SEQ ID No. combinations. Dependent claims refine the construct by adding structural constraints, narrowing to treating infection, specifying pathogen categories, and enumerating administration routes, while keeping the core TIM-1 and DC-SIGN fusion architecture.
Ig-Fc fusion construct with PS-binding TIM-1 and DC-SIGN PAMP recognition
A fusion construct comprising an Ig-Fc domain, a peptide, protein or antibody fragment binding to phosphatidylserine selected from TIM-1 and fragments thereof, and a peptide or protein binding to and/or recognizing a PAMP expressed by a microbe selected from DC-SIGN and fragments thereof, with first-chain sequences according to SEQ ID No.: 1 or SEQ ID No.: 2 and SEQ ID No.: 38, and second-chain sequences according to SEQ ID No.: 3 or SEQ ID No.: 4 and SEQ ID No.: 40.
Dimeric Ig-Fc with heterodimerization mutations at positions 405 and/or 409
The fusion construct includes an Ig-Fc domain that is dimeric and contains heterodimerization mutations at positions 405 and/or 409 (EU numbering).
Fusion construct intended for treating an infection
The fusion construct is intended for treating an infection.
Infection caused by virus, parasite, bacteria, fungi or protozoan
The infection addressed is caused by a virus, a parasite, a bacteria, a fungi or a protozoan.
Bacteria selected as Mycobacterium tuberculosis and Mycobacterium leprae
The bacteria used is selected from Mycobacterium tuberculosis and Mycobacterium leprae.
Administration route selected from specified routes
The fusion construct is configured to be administered via one of the listed administration routes selected from subcutaneous, intradermal, intramuscular, oral, and nasal administration.
Overall, the claim set centers on an Ig-Fc fusion construct that simultaneously binds phosphatidylserine via TIM-1 and recognizes a microbe-associated PAMP via DC-SIGN, with specific first- and second-chain sequence embodiments. Dependent claims add engineered Ig-Fc dimer and heterodimerization constraints, define treatment of infections, expand infection scope to multiple pathogen categories, narrow specific bacteria targets to Mycobacterium tuberculosis and Mycobacterium leprae, and enumerate administration routes.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating infections across pathogen categories including virus, parasite, bacteria, fungi and protozoan.
Treating infections with bacteria selected from Mycobacterium tuberculosis and Mycobacterium leprae.
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