Polynucleotide, polypeptide with immunosuppressive activity, expression cassette, expression vector, host cell, pharmaceutical composition, methods for producing a polypeptide with immunosuppressive activity and for preventing or treating conditions that require immunosuppression, and use of a polypeptide
Inventors
Tambourgi, Denise V. • Queiroz, Giselle Pidde • Sant'Anna, Osvaldo Augusto Brazil Esteves • Magnoli, Fábio Carlos • Pacheco, Ogari de Castro
Assignees
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Publication Number
US-10081660-B2
Publication Date
2018-09-25
Expiration Date
Abstract
This invention refers to polynucleotides and non-hemorrhagic and non-immunogenic polypeptides of selective immunosuppressive activity on production of antibodies to antigens of different natures. The polypeptides described herein are useful for preparing pharmaceutical compositions for prevention or treatment of conditions that require immunosuppression, preferably, inflammatory, autoimmune, allergic and infectious diseases and rejection to transplanted organs.
Core Innovation
The invention relates to immunosuppressive, non-hemorrhagic, non-immunogenic polypeptides derived from Lachesis muta venom. The disclosed polypeptides comprise the amino acid sequences of SEQ ID NO: 2 or SEQ ID NO: 3, and also include polypeptides having variants defined by sequence identity, together with pharmaceutical compositions comprising these polypeptides or pharmaceutically acceptable salts.
The disclosure focuses on immunosuppressive polypeptides derived from Lachesis muta venom and associated with Lachesis factor LHF-II and reprolysin/SVMP metalloproteinase activity. It addresses the need for immunosuppressive polypeptides suitable for treating inflammatory, autoimmune, allergic, infectious diseases and transplant rejection without hemorrhagic or immunogenic effects.
Experimental work identifies and characterizes target polypeptide factors and their relationship to LHF-II/reprolysin metalloproteinases, including structural modeling used to design immunosuppressive fragments. The document states that assays show lack of proteolytic/hemorrhagic activity and low or no immunogenicity by ELISA, and functional immunosuppressive outcomes are demonstrated in mouse antibody production models. Immunosuppressive activity is also described for specific fragments, including SEQ ID NOs: 4-15 and fragments such as P2 and P6.
Claims Coverage
The independent claim covers polypeptides defined by specific amino acid sequences, with 3 main inventive additions in the claim set: pharmaceutical composition with carrier or excipient, inclusion of an additional therapeutic agent, and production using an expression cassette with promoter and transcription terminator, including an optional tag requirement.
Polypeptide with SEQ ID NO: 2 or SEQ ID NO: 3
A polypeptide, or a pharmaceutically acceptable salt thereof, wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 3.
Pharmaceutical composition with pharmaceutically acceptable carrier or excipient
A pharmaceutical composition comprising the polypeptide, or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier or excipient.
Pharmaceutical composition with additional therapeutic agent
A pharmaceutical composition comprising the polypeptide, or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier or excipient and an additional therapeutic agent.
Production using host cell with expression cassette and isolating from cell or culture media
A method for producing a polypeptide by providing a host cell with an expression cassette wherein a polynucleotide encoding the polypeptide is operably linked to a promoter and a transcription terminator, cultivating the cell under conditions that support production, and isolating the polypeptide from the cell or culture media.
Tagged polypeptide production
A method for producing a tagged polypeptide by providing a host cell with an expression cassette wherein a polynucleotide encoding the polypeptide is operably linked to a promoter and a transcription terminator, cultivating the cell under conditions for production, and isolating the polypeptide from the cells or culture media, wherein the produced polypeptide further comprises a tag.
Overall, the claim set is directed to immunosuppressive polypeptides defined by SEQ ID NO: 2 or SEQ ID NO: 3, with coverage extending to pharmaceutical formulations, optional combination with an additional therapeutic agent, and production via a host cell expression cassette using promoter and transcription terminator elements, including a variant that requires a tag.
Stated Advantages
Immunosuppressive activity.
Non-hemorrhagic polypeptides.
Non-immunogenic or low immunogenic potential.
Documented Applications
Therapeutic and preventive use for inflammatory diseases.
Therapeutic and preventive use for autoimmune diseases.
Therapeutic and preventive use for allergic diseases.
Therapeutic and preventive use for infectious diseases.
Use for transplant rejection.
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