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US-12617841-B2 - Nucleic acid antibody constructs for use against respiratory syncytial virus

US12617841B2US 12617841 B2US12617841 B2US 12617841B2US-12617841-B2

Abstract

Disclosed herein is a composition including a recombinant nucleic acid sequence that encodes an antibody to a Respiratory Syncytial Virus antigen. Also disclosed herein is a method of generating a synthetic antibody in a subject by administering the composition to the subject. The disclosure also provides a method of preventing and/or treating an Respiratory Syncytial virus infection in a subject using the composition and method of generation.

Inventors

  • David Weiner
  • Kar Muthumani
  • Jing Chen
  • Trevor Smith
  • Katherine SCHULTHEIS

Assignees

  • THE WISTAR INSTITUTE OF ANATOMY AND BIOLOGY
  • INOVIO PHARMACEUTICALS, INC.

Dates

Publication Date
20260505
Application Date
20190131

Claims (8)

  1. 1 . A composition comprising a nucleic acid molecule encoding a synthetic antibody and hyaluronidase, wherein the nucleic acid molecule comprises a nucleotide sequence encoding ScFv anti-RSV-F synthetic antibody, wherein the nucleic acid molecule comprises nucleotides 742-2220 of SEQ ID NO: 2.
  2. 2 . The composition of claim 1 , wherein the nucleic acid molecule further comprises a nucleotide sequence encoding a cleavage domain.
  3. 3 . The composition of claim 1 , wherein the nucleic acid molecule comprises the nucleotide sequence of SEQ ID NO: 2.
  4. 4 . The composition of claim 1 , wherein the nucleic acid molecule further comprises a nucleotide sequence encoding a leader sequence.
  5. 5 . The composition of claim 1 , wherein the nucleic acid molecule comprises an expression vector.
  6. 6 . The composition of claim 1 , further comprising a pharmaceutically acceptable excipient.
  7. 7 . A formulation comprising the composition of claim 1 .
  8. 8 . A method of treating Respiratory Syncytial virus infection in a subject, the method comprising administering to the subject the composition of claim 1 .

Description

TECHNICAL FIELD The present invention relates to a composition comprising a recombinant nucleic acid sequence for generating one or more synthetic antibodies, and functional fragments thereof, in vivo, and a method of preventing and/or treating viral infection in a subject by administering said composition. CROSS-REFERENCE TO RELATED APPLICATIONS This application is a U.S. national phase application filed under 35 U.S.C. § 371 claiming priority to International Patent Application No. PCT/US19/15975, filed Jan. 31, 2019, which is entitled to priority under 35 U.S.C. § 119(e) to U.S. Provisional Application No. 62/624,320, filed Jan. 31, 2018, and U.S. Provisional Application No. 62/749,580, filed Oct. 23, 2018, the contents of each of which are incorporated by reference herein in their entireties. REFERENCE TO A “SEQUENCE LISTING,” A TABLE, OR A COMPUTER PROGRAM LISTING APPENDIX SUBMITTED AS AN ASCII TEXT FILE The present application hereby incorporates by reference the entire contents of the text file named “206193-0111-00US_Sequence_Listing_v2.txt” in ASCII format. The text file containing the Sequence Listing of the present application was created on Sep. 25, 2024, and is 39,491 bytes in size. BACKGROUND Respiratory Syncytial virus (RSV) is a major threat to the health of young children and elderly adults, and complications involved with lower respiratory infections can lead to hospitalization and, some patients may succumb to disease. Almost the entire population is infected with the virus during the first years of life, but immunity in many cases is not sustained nor completely protective against following infections. Even though a vaccine remains an unmet need, passive immunization with an immunoprophylactic anti-RSV-F antibody (Pavilizumab) has successfully reduced hospitalizations in vulnerable patients. However, the use of this monoclonal Antibody (mAb) is limited to high resource settings and unavailable to the majority of the global at risk populations. While mAbs have been shown to be effective in providing protection against many infectious diseases their widespread use is limited. The limited in vivo half-life means multiple doses are required to maintain immunity, and the high costs and complexities involved in development, manufacture and distribution also hinder their global use. In response, new strategies based on the in vivo delivery of antibody genes are being developed. One such platform is dMAb, a synthetic DNA-encoded mAb delivered by electrogenetransfer in vivo and utilizing the body's own muscle cells to generate and secrete the protein immunoglobulin. Other than protein-based drugs, plasmid DNA is inexpensive to manufacture and because of its temperature stability it would not require a cold chain, which makes it ideal for global distribution. In proof-of principle studies this platform provided protection against various infectious diseases, including influenza, pseudomonas and Ebola in pre-clinical animal models. Thus, there is need in the art for improved therapeutics that prevent and/or treat RSV infection. The current invention satisfies this need. SUMMARY The present invention is directed to a nucleic acid molecule encoding one or more synthetic antibodies, wherein the nucleic acid molecule comprises at least one selected from the group consisting of a) a nucleotide sequence encoding an anti-respiratory syncytial virus (RSV) synthetic antibody; b) a nucleotide sequence encoding a fragment of an anti-RSV synthetic antibody; c) a nucleotide sequence encoding ScFv anti-RSV synthetic antibody; and d) a nucleotide sequence encoding a fragment of a ScFv anti-RSV synthetic antibody. In one embodiment, the invention relates to a nucleic acid molecule encoding a ScFv anti-RSV DMAb or a fragment or variant thereof. In one embodiment, the invention relates to a nucleic acid molecule encoding an anti-RSV antibody or a fragment or variant thereof. In one embodiment, the synthetic antibody binds to an RSV antigen. In one embodiment, the synthetic antibody binds to one or more RSV antigens selected from RSV-F, RSV-G, RSV-Ga, RSV-Gb, RSV-M2-1, RSV M2-2, and any combination thereof. In one embodiment, the nucleic acid molecule comprises nucleotide sequence encoding a cleavage domain. In one embodiment, the nucleic acid molecule comprises a nucleotide sequence encoding an amino acid sequence at least 90% homologous to an amino acid sequence selected from the group consisting of: SEQ ID NO:7 and an amino acid sequence encoded by one of SEQ ID NOs: 1-6; or a fragment of an amino acid sequence at least 90% homologous to an amino acid sequence selected from the group consisting of SEQ ID NO:7 and an amino acid sequence encoded by one of SEQ ID NOs: 1-6. In one embodiment, the nucleic acid molecule comprises a nucleotide sequence at least 90% homologous to SEQ ID NOs: 1-6 or a fragment of a nucleotide sequence at least 90% homologous to SEQ ID NOs: 1-6. In one embodiment, the nucleotide sequence en