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EP-4739342-A1 - COMPOSITIONS AND METHODS FOR TREATMENT OF SYSTEMIC LUPUS ERYTHEMATOSUS

EP4739342A1EP 4739342 A1EP4739342 A1EP 4739342A1EP-4739342-A1

Abstract

The present invention relates to a microbe or microbe like particle comprising a peptide having an SLE therapeutic efficacy, an analog or a fragment thereof, wherein the peptide is displayed on the surface of the microbe or microbe like particle.

Inventors

  • GOLDSTAUB, DAN

Assignees

  • Goldstaub, Dan

Dates

Publication Date
20260513
Application Date
20240703

Claims (20)

  1. 1. A microbe-based drug delivery system comprising a microbe or microbe like particle; and a peptide having a systemic lupus erythematosus (SLE) therapeutic efficacy, wherein said peptide is displayed on the surface of said microbe or microbe like particle.
  2. 2. The microbe-based drug delivery system according to claim 1, wherein said peptide is having a sequence selected from SEQ ID NOS: 1 -24, an analog or a fragment thereof.
  3. 3. The microbe-based drug delivery system according to claim 2, wherein the peptide is having a sequence selected from SEQ ID NO: 1 (GYYWSWIRQPPGKGEEWIG), SEQ ID NO: 2 (FIEWNKLRFRQGLEW), and SEQ ID NO: 13 (HGYYWSWIRQPPGKGLEWI), an analog or a fragment thereof.
  4. 4. The microbe-based drug delivery system according to any one of claims 1-3, which is devoid of at least part of the genetic material belonging to said microbe.
  5. 5. The microbe-based drug delivery system according to any one of claims 1-4, wherein the microbe is nonpathogenic to a mammal.
  6. 6. The microbe-based drug delivery system according to any one of claims 1-5, wherein the microbe is at least one of (i) selected from a virus, a bacteriophage, a fungi, and/or a bacterium; and (ii) non-pathogenic to mammals.
  7. 7. The microbe-based drug delivery system according to any one of claims 1-6, wherein the peptide is coupled to a surface protein of the microbe or microbe like particle.
  8. 8. The microbe-based drug delivery system according to claim 7, wherein the peptide is coupled to a surface protein of the microbe or microbe like particle indirectly via a linker or directly.
  9. 9. The microbe-based drug delivery system according to claim 7, wherein the microbe is a virus or virus like particle and wherein the peptide is coupled to a coat protein of said virus or virus like particle.
  10. 10. The microbe-based drug delivery system according to any one of claims 1-9, wherein the microbe is a virus.
  11. 11. The microbe-based drug delivery system according to claim 10, wherein the virus is a plant virus.
  12. 12. The microbe-based drug delivery system according to claim 11, wherein the plant virus is selected from a group consisting of: tobacco mosaic virus (TMV), cowpea mosaic virus (CPMV), cowpea chlorotic mottle virus (CCMV), physalis mottle virus (PhMV), brome mosaic virus, red clover necrotic mosaic virus (RCNMV), hibiscus chlorotic virus, and potato virus X (PVX).
  13. 13. The microbe-based drug delivery system according to claim 12, wherein the plant virus is a tobacco mosaic virus (TMV).
  14. 14. The microbe-based drug delivery system according to claim 10, wherein the virus is a mammalian virus selected from a group consisting of: Hepatitis B Virus (HBV), Human Immunodeficiency Virus (HIV), Human Papillomavirus (HPV), Coxsackievirus A16 (CA16), a Poliovirus Virus-Like particle, and Enterovirus 71 (EV71).
  15. 15. The microbe-based drug delivery system according to any one of claims 1-14, wherein the microbe or microbe like particle comprises an expression vector comprising a nucleic acid sequence encoding a peptide selected from SEQ ID NOS: 1-24, an analog or a fragment thereof.
  16. 16. The microbe-based drug delivery system according to any one of claims 1-15, wherein the peptide is having at least 80 % sequence identity to SEQ ID NOS: 1-24.
  17. 17. The microbe-based drug delivery system according to claim 16, wherein the peptide is having at least 90 % sequence identity to SEQ ID NOS: 1 -24.
  18. 18. A pharmaceutical composition comprising a plurality of microbe-based drug delivery system of any one of claims 1-17, and a pharmaceutically acceptable carrier.
  19. 19. A method of introducing into a cell a peptide having an SLE therapeutic efficacy, the method comprising contacting the cell with the pharmaceutical composition of claim 18.
  20. 20. A method of delivering into a subject a peptide having an SLE therapeutic efficacy, the method comprising administering to the subject the pharmaceutical composition of claim 18.

Description

COMPOSITIONS AND METHODS FOR TREATMENT OF SYSTEMIC LUPUS ERYTHEMATOSUS SEQUENCE LISTING STATEMENT The instant application contains a Sequence Listing which has been submitted electronically in XML format and is hereby incorporated by reference in its entirety. Said XML copy, created on June 26, 2023, is named 16301-PC Sequence Listings. xml and is 27 Kilobytes in size. TECHNICAL FIELD OF THE INVENTION The present invention is in the field of pharmaceutical compositions and methods of treatment of a disease. In particular, the invention relates to drug delivery systems for treating systemic lupus erythematosus (SLE) and to peptides effective in the treatment of SLE. BACKGROUND OF THE INVENTION Systemic lupus erythematosus (SLE) is an autoimmune disease caused by the 'selfattack' of the immune system against body antigens, resulting in inflammation and tissue damage. It can manifest in a chronic manner or be of a form that has recurrent relapses. SLE is characterized by the presence of an array of autoantibodies, including antibodies to DNA, antibodies to nuclear antigens, and antibodies to ribonucleoproteins. It has the potential of affecting multiple organ systems including the skin, muscles, bones, lungs, kidneys, cardiovascular and central nervous systems. Renal complications, infections, myocardial infarction and central nervous system involvement are the major causes of morbidity and even death in SLE patients. To date there is no definitive treatment or cure for SLE which is devoid of detrimental side effects associated with immunosuppression. In recent years some peptide-based therapies for SLE have been developed and clinically tested. An artificial peptide (a.k.a. "consensus" peptide [pCONS]) was developed using an algorithm that defines the T cell stimulatory amino acid sequences from the VH region of multiple BWFlIgG antibodies to DNA. The peptide illustrated a delay in the appearance of autoantibodies and prolonged survival in mice. Bevra H. Hahn el al. Arthritis & Rheumatism, Vol. 44, No. 2, February 2001, pp432-441. International Patent Application Publication No. WO 1996/030057 discloses synthetic peptides based on a complementarity -determining region (CDR) of the heavy or light chain of a pathogenic anti-DNA monoclonal antibody that induces a systemic lupus erythematosus (SLE)-like disease in mice, and pharmaceutical compositions comprising said peptides for the treatment of SLE in humans. International Patent Application Publication No. WO 2002/067848 discloses peptides based on the complementarity-determining region of the human monoclonal anti-DNA 16/6Id antibody capable of immunomodulating SLE associated responses. In particular, peptides based on the CDR1 and CDR3 of the human 16/6Id were found to inhibit the proliferative response of peripheral blood lymphocytes (PBL) of SLE patients to the human anti-DNA 16/61d mAB, and to ameliorate disease manifestations of mice afflicted with spontaneous or experimental SLE. International Patent Application Publication Nos. WO 2004/064788 and WO 2004/064787 disclose aqueous pharmaceutical compositions of peptides derived from the complementarity-determining region of the human monoclonal anti-DNA 16/6Id. Peptide based therapies are known to be efficacious but also suffer from some unfavorable characteristics mainly regarding their pharmacokinetic behavior, including plasma stability, membrane permeability and circulation half-life. In recent years an immense advancement has been made in the field of drug delivery, inter alia, in microbe-based drug delivery systems for treating various diseases. Viral nanoparticles (VNPs) encompass a diverse array of naturally occurring nanomaterials that can encapsulate active ingredients or be genetically or chemically conjugated to such active ingredients. Microbe-based drug delivery systems are manufactured through scalable fermentation or molecular farming and are biocompatible and biodegradable. These properties have led to a wide range of applications, including cancer therapies, immunotherapies, vaccines, antimicrobial therapies, cardiovascular therapies, gene therapies, as well as imaging and theragnostic (Young Hun Chung et al. Adv Drug Deliv Rev. 2020;156:214-235). There is a need for new and effective delivery systems of peptides that will provide enhanced retention and efficacy in treating SLE. SUMMARY OF THE INVENTION In one aspect, the present invention provides a microbe-based drug delivery system comprising a microbe or microbe like particle; and a peptide having a systemic lupus erythematosus (SLE) therapeutic efficacy, wherein said peptide is displayed on the surface of said microbe or microbe like particle. In one or more embodiments, the peptide is having a sequence selected from SEQ ID NOS: 1-24, an analog or a fragment thereof. In one or more embodiments, the peptide is having a sequence selected from SEQ ID NO: 1 (GYYWSWIRQPPGKGEEWIG), SEQ ID NO: 2 (pCONS- FIEWNKLRFRQGLEW), and SEQ ID NO: