DPP3 binder directed to and binding to specific DPP3-epitopes and its use in the prevention or treatment of diseases / acute conditions that are associated with oxidative stress
Inventors
Assignees
Publication Number
US-11530276-B2
Publication Date
2022-12-20
Expiration Date
2038-10-24
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Abstract
The present invention provides binder directed to and binding to a DPP3 protein or functional derivative thereof and its use in a method of prevention or treatment of diseases or acute conditions in a patient, wherein said disease or acute condition is associated with oxidative stress. With this context, specifically the present invention provides a binder being directed to and binding to an epitope according to SEQ ID NO.: 2, wherein said epitope is comprised in a DPP3 protein or a functional derivative thereof, and wherein said DPP3 binder recognizes and binds to at least three amino acids of SEQ ID NO.: 2.
Core Innovation
The invention provides a binder directed to and binding to a dipeptidyl peptidase 3 (DPP3) protein or a functional derivative thereof, specifically to an epitope according to SEQ ID NO.: 2. The binder recognizes and binds to at least three amino acids of this epitope, which is comprised within the DPP3 protein. The binder can be an antibody, antibody fragment, or non-Ig scaffold, and is useful in the prevention or treatment of diseases or acute conditions associated with oxidative stress.
The problem being solved is that oxidative stress plays a critical role in a wide range of diseases and acute conditions, including neurodegenerative diseases, metabolic syndrome, cardiovascular disorders, autoimmune diseases, inflammatory lung diseases, kidney diseases, liver diseases, digestive diseases, viral infectious diseases, cancer, inflammation, sepsis, septic shock, and systemic inflammatory response syndrome (SIRS). Existing treatments are insufficient for regulating oxidative stress effectively in these conditions. The invention addresses this by providing DPP3 binders that reduce or regulate oxidative stress by specifically targeting an epitope of DPP3, thereby opening new therapeutic avenues.
Claims Coverage
The patent contains seven independent claims focused on a DPP3 binder with specific binding characteristics and therapeutic applications, covering antibody formats and binding epitopes.
DPP3 binder with specificity to epitope SEQ ID NO.: 2
A dipeptidyl peptidase 3 (DPP3) binder directed to and binding to an epitope according to SEQ ID NO.: 2, binding at least three amino acids of SEQ ID NO.: 2 within SEQ ID NO.: 1, with affinity constant of at least 10⁷ M⁻¹. The binder is a monoclonal antibody or antigen binding fragment with specified heavy chain CDRs (SEQ ID NO.: 7, 8, 9) and light chain CDRs (SEQ ID NO.: 10, KVS, 11).
Binding to additional epitopes SEQ ID NO.: 3
The binder further specifically binds to an epitope according to SEQ ID NO.: 3, recognizing at least three amino acids of SEQ ID NO.: 3.
Binding to epitope SEQ ID NO.: 4
The binder further specifically binds to an epitope according to SEQ ID NO.: 4, recognizing at least three amino acids of SEQ ID NO.: 4.
Binder selected from antibody, antigen binding fragment, or non-Ig scaffold
The DPP3 binder is selected from the group comprising antibodies, antigen binding fragments, or non-Ig scaffolds.
Monospecific binder selection
The binder may also be selected from monospecific antibodies, antigen binding fragments, or monospecific non-Ig scaffolds.
Humanized monoclonal antibody binder
The DPP3 binder may be a humanized monoclonal antibody or antigen binding fragment comprising heavy chain sequence SEQ ID NO.: 12 and light chain sequence SEQ ID NO.: 13.
The claims cover specific DPP3 binders that target defined epitopes within DPP3 with high affinity, including monoclonal and humanized antibodies, antibody fragments, and non-Ig scaffolds, intended for therapeutic use in oxidative stress associated diseases.
Stated Advantages
The binder rapidly reduces or regulates oxidative stress in the cells of mammals.
The invention provides selective and specific binders that can be used for prevention or treatment of diseases or acute conditions associated with oxidative stress.
The binder may act as a secondary medicament reducing oxidative stress induced as a side effect by primary drug treatments.
Documented Applications
Prevention or treatment of diseases or acute conditions associated with oxidative stress, including neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis).
Treatment of metabolic syndrome and its components such as insulin resistance, obesity, hyperglycemia, dyslipidemia, hypertension, and diabetes.
Therapy for cardiovascular disorders including atherosclerosis, hypertension, heart failure, cardiovascular ischemia, cerebral ischemic injury, stroke, and myocardial infarction.
Treatment of autoimmune diseases like rheumatoid arthritis and systemic lupus erythematosus.
Managing inflammatory lung diseases such as COPD and asthma.
Treatment of kidney diseases including renal toxicity (drug-induced kidney disease), acute kidney injury, chronic kidney disease, diabetic nephropathy, and end-stage renal disease.
Treatment of liver diseases such as hepatotoxicity, viral hepatitis, and cirrhosis.
Treatment of digestive diseases like inflammatory bowel diseases (Ulcerative colitis, Crohn's disease), gastritis, pancreatitis, and peptic ulcer.
Treatment of viral infectious diseases including blood-borne hepatitis viruses (B, C, and D), HIV, influenza A, Epstein-Barr virus, and respiratory syncytial virus.
Treatment of various cancers including prostate, breast, lung, colorectal, bladder, ovarian, skin, stomach, and liver cancer.
Treatment of inflammation, sepsis, septic shock, and systemic inflammatory response syndrome (SIRS).
Use as secondary medicament in combination with drugs causing oxidative stress as a side effect to regulate induced oxidative stress and resultant toxicities.
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