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US-20260124148-A1 - POLYPEPTIDE FORMULATIONS FOR ORAL DELIVERY

US20260124148A1US 20260124148 A1US20260124148 A1US 20260124148A1US-20260124148-A1

Abstract

The present disclosure provides, among other things, methods and compositions for the oral administration of polypeptides. Many polypeptides are typically administered in liquid solutions by intravenous or subcutaneous injection. The present disclosure provides methods and compositions that include a polypeptide formulation, e.g., truffle, tablet, globule, candy, capsule formulation suitable for oral administration, where the formulation includes an amorphous polypeptide composition or a crystallized polypeptide composition and a pharmaceutically acceptable carrier.

Inventors

  • Bhami Shenoy
  • Suryakanth Motilal Pai

Assignees

  • Bhami's Research Laboratory, Pvt. Ltd.

Dates

Publication Date
20260507
Application Date
20251230
Priority Date
20221014

Claims (20)

  1. 1 . A polypeptide formulation for oral delivery comprising: (1) a carrier polypeptide composition; (2) an active polypeptide composition; and optionally (3) a pharmaceutically acceptable carrier.
  2. 2 . The polypeptide formulation of claim 1 , wherein the polypeptide formulation is a truffle formulation comprising a core and a pharmaceutically acceptable shell, wherein: the core comprises (1) a carrier polypeptide composition and (2) an active polypeptide composition.
  3. 3 . The polypeptide formulation of claim 1 , wherein the polypeptide formulation is a tablet formulation.
  4. 4 . The polypeptide formulation of claim 1 , wherein the polypeptide formulation is a globule formulation.
  5. 5 . The polypeptide formulation of claim 1 , wherein the polypeptide formulation is a candy formulation.
  6. 6 . The polypeptide formulation of claim 5 , wherein the candy formulation is in a form of candy gems, chewing gum, gummy candy, hard candy (e.g., drops, lollipops, lozenges, rock candy, stick candy, etc.) marshmallows, syrup, or toffee.
  7. 7 . The polypeptide formulation of claim 6 , wherein the candy formulation is in a form of drop, film, gel, patch, spray, or wafer.
  8. 8 . The polypeptide formulation of claim 1 , wherein the polypeptide formulation is a capsule formulation, optionally wherein the capsule formulation comprises a core and a pharmaceutically acceptable shell.
  9. 9 . The polypeptide formulation of claim 8 , wherein the capsule formulation comprises a pharmaceutically acceptable carrier comprising a Vitamin E agent.
  10. 10 . The polypeptide formulation of any one of claims 1-9 , wherein the active polypeptide composition is embedded in a carrier polypeptide composition.
  11. 11 . A method of delivering a polypeptide to the bloodstream of a subject, the method comprising orally administering to the subject a polypeptide formulation of any one of claims 1-10 .
  12. 12 . The method of claim 11 , wherein the polypeptide is delivered to the bloodstream through mouth tissue, optionally wherein the polypeptide is delivered to the blood stream via buccal or sublingual administration.
  13. 13 . A method of delivering a polypeptide to mouth tissue of a subject, the method comprising orally administering to the subject a polypeptide formulation of any one of claims 1-10 .
  14. 14 . A method of producing a polypeptide formulation of any one of claims 1-10 , the method comprising crystallizing the carrier polypeptide composition and the active polypeptide composition, wherein the active polypeptide is embedded in the carrier polypeptide during crystallization.
  15. 15 . The polypeptide formulation or method of any one of claim 1-14 , wherein the active polypeptide composition is or comprises a therapeutic polypeptide/peptide, optionally wherein the therapeutic polypeptide/peptide is or comprises: (i) an antibody agent or antigen-binding portion thereof, (ii) a monoclonal antibody or fragment thereof; (iii) a fusion polypeptide; (iv) an immunoglobulin; (v) an enzyme; (vi) a hormone; (vii) a cytokine; or (viii) an analog or combination of any of (i)-(vii), optionally wherein the polypeptide/peptide is modified by one or more of pegylation, acetylation, amidation, lipidation, methylation, phosphorylation, glycosylation, glycation, sulfation, mannosylation, nitrosylation, acylation, palmitoylation, prenylation, fatty acids, or a combination thereof.
  16. 16 . The polypeptide formulation or method of any one of claims 1-15 , wherein the polypeptide of the active polypeptide composition is selected from Abaloparatide (Tymlos), Adlyxin Lixisenatide®, Afamelanotide Scenesse®, Angiotensin II (Giapreza), Angiotension 11 antagoist, Anidulafungin, Atosiban, Aviptadil, Belantamab mafodotin-blmf (Blenrep™) Bentiromide, Beta-endorphin, Bivalirudin, Bradykynin, Bremelanotide Vyleesi®, Bursin, Calcitonin, Capreomycin, Carbetocin, Carfilzomib, Caspofungin, Ceruletide, Cholecystokynin, Cu-DOTATATE (Detectnet™), Dalbavancin, Daptomycin, Degarelix, Dulaglutide, Edotreotide, Edotreotide gallium Ga-68, Enfortumab Vedotin-Ejfv PADCEV®, Enfuvirtide, Etelcalcetide (Parsabiv), Exenatide, Ga DOTA-TOC, gallium Ga-68, Ga-PSMA-11, Glatiramer acetate, Glatiramer, Glucagon, Gonadorelin, Goserelin, Goserilin, Gramicidin, Human growth harmone, Icatibant, Imcivree™, Insulin degludec Tresiba®, Interferons, Interferon Alfa-2a, Recombinant, Interferon alfacon-1, Interferon Alfa-2b, Recombinant, Interferon beta-1b, Interferon beta-1a, Interferon alfa-n3, Interferon alfa-n1, Interferon gamma-1b, Peginterferon alfa-2b, Peginterferon alfa-2a, Insulin, Ixazomib Ninlar®, Lanreotide, Leuprorelin, Leuprotide, Linaclotide, Liraglutide, Lu DOTA-TATE Lutathera®, Lumasiran (Oxlumo™), Lupkynis™ LUPRON DEPOT, Lutetium Lu 177 dotatate4, Macimorelin (Macrilen), Micafungin, Mifamurtide, Mycappsa®, Scenesse®, Nesiritide, Octreotide, Oritavancin, Oxytocin, Pasireotide, Plecanatide Trulance®, Polatuzumab Vedotin-Piiq Polivy®, Pramlintide, Romidepsin, Voclosporin, Romiplostim, Rybelsus®, Sandostatin, Secretin human, Semaglutide, Sermorelin, Setmelanotide (Imcivree™), Somatuline, Taltirelin, Teduglutide, Telavancin, Teriparatide, Terlipressin, Tetracosactide, Bacitracin, Vancomycin, Thymalfasin, Mecasermin, Cetrorelix, Vasopressin, Victoza, Viltolarsen (Viltepso™), Vyleesi®, Zegalogue, Ziconotide, Lupkynis™ Zoladex, Desmopressin. Insulin degludec Tresiba®, Ixazomib Ninlar®, Macimorelin Macrilen®, 177Lu DOTA-TATE Lutathera®, 68Ga DOTA-TOC, Insulin recombinant, Exentide (Byetta), Lancreotide (Somatuline), Pramilintide (Symlin), Etanercept, Bevacizumab, Rituximab, Infliximab, Trastuzumab, Insulin glargine, Epoetin alfa, Darbepoetin alfa, Epoetin beta, Pegfilgrastim, Ranibizumab, Insulin aspart, Rhu insulin, Octocog alfa, Insulin lispro, Cetuximab, Eptacog alfa, Onabotulinumtoxin A, Filgrastin, Insulin detemir, Natalizumab, nsulin (humulin), Palivizumab, Bleomycin, Bortezomib Blenoxane, Buserelin, Carfilzomib, Cobicistat, Corticotropin, Cosyntropin, Cyclosporia, Dactinomycin, Depreotide, Eptifibatide, Ganirelix, Glutathion, Histrelin, Leuprolide, Lucinactant, Lypressin, Nafarelin, Pentagastrin, Pentetreotide, Polymyxin B, Protirelin, Saralasin, Secretin porcine, Sincalide, Somatorelin, Somatostatin, Teicoplanin, Triptorelin, Urofollitropin, Abarelix, Pegvisomant, Somatropin recombinant, Lutropin alfa, Follitropin beta, Menotropins, Thyrotropin Alfa, Choriogonadotropin alfa, Aldesleukin, Coagulation Factor IX, Antihemophilic Factor, Eptifibatide, Exenatide Bydureon, Lepirudin, Angiotensin 1-7, Boceprevir Victrelis, Kyprolis, Ciclosporin Ikervis, Ciclosporin Verkazia, Dalbavancin Xydalba, Lutetium (177Lu) oxodotreotide Lutathera, Ombitasvir (paritaprevir and ritonavir) Viekirax, Televancin Vibativ, Avexitide, Calcitonin gene-related peptide, Corticorelin, Leptin, Aclerastide, Albusomatropin, Anamorelin, G17DT, Insulin peglispro, Lenomorelin, Selepressin, Somapacitan, Taspoglutide, Thymosin beta-4, Tirzepatide, Ularitide, Vosoritide, Zoptarelin doxorubicin, Bombesin, Cenderitide, Deslorelin, Gastric inhibitory polypeptide, MK-3207, Olcegepant, Pancreatic Polypeptide, Peptide YY (3-36), Pirnabine, Somatoprim, TT-232, BPI-3016, NBI-6024, Albiglutide, Taltirelin hydrate, Tesamorelin, Peginesatide, Cyclosporin A, Chiasma, Plecanotide, Colistin sulfate, Tyrothricin, Pancrelipase, Tilactase, Sacrosidase, Diamine oxidase, NOBEX insulin by the Palmitoylatios, Thymopentin, β-LGDP, PTH1-34, BSA, sCT, hGH, BSM, Captopril, Enfurvitide, Streptokinase, Dolcanatide, Efpeglenation-Sanofi, MEDI4166-Astra Zeneca, or PF-06836922(MOD-4023)-Pfizer, adalimumab (HUMIRA®), or an analog or derivative thereof, optionally wherein the polypeptide is natural, synthetic, or engineered.
  17. 17 . The polypeptide formulation or method of any one of claims 1-16 , wherein the polypeptide of the active polypeptide composition is insulin, Lantus, parathyroid hormone (PTH), liraglutide, octreotide acetate, semaglutide, adalimumab (HUMIRA®), or trastuzumab, or an analog or derivative thereof, optionally wherein the polypeptide is natural, synthetic, or engineered.
  18. 18 . The polypeptide formulation or method of any one of claims 1-17 , wherein the polypeptide of the active polypeptide composition has a molecular weight between about 100 Da and 200 kDa, optionally wherein the molecular weight is between about 500 Da and about 70 kDa, about 5 kDa and about 2,000 kDa, about 10 kDa and about 500 kDa, about 20 kDa and about 500 kDa, about 100 kDa and about 150 kDa, or about 150 kDa and about 200 kDa.
  19. 19 . The polypeptide formulation or method of any one of claims 1-18 , wherein the active polypeptide composition comprises about 1 μg to about 2,000 mg of the polypeptide, optionally wherein the active polypeptide composition comprises about 1 μg to about 1,000 mg, about 1 μg to about 500 mg, about 1 μg to about 400 mg, about 1 μg to about 300 mg, about 1 μg to about 200 mg, about 1 μg to about 100 mg, about 1 μg to about 50 mg, about 1 μg to about 25 mg, about 1 μg to about 20 mg, about 1 μg to about 15 mg, about 1 μg to about 10 mg, about 1 μg to about 5 mg, about 1 μg to about 1 mg, about 1 μg to about 500 μg, about 1 μg to about 250 μg, about 1 μg to about 200 μg, about 1 μg to about 150 μg, about 1 μg to about 100 μg, about 1 μg to about 50 μg, about 1 mg to about 1,000 mg, about 1 mg to about 500 mg, about 1 mg to about 400 mg, about 1 mg to about 300 mg, about 1 mg to about 200 mg, about 1 mg to about 100 mg, about 1 mg, to about 50 mg, about 1 mg to about 25 mg of the polypeptide.
  20. 20 . The polypeptide formulation or method of any one of claims 1-19 , wherein the carrier polypeptide composition comprises or is amylase.

Description

CROSS-REFERENCE TO RELATED APPLICATION This application claims priority to Indian Application No. 202241058759, filed Oct. 14, 2022 and Indian Application No. 202341022184, filed Mar. 27, 2023, the entirety of each of which is incorporated herein by reference. BACKGROUND Polypeptide therapeutics play an important role in medicine. Many current therapeutics include polypeptides such as enzymes, hormones, and antibodies. A typical route of administration for polypeptide therapeutics is intravenous or subcutaneous injection. Crystallization of polypeptides presents certain challenges. For example, a new set of Crystallization conditions need to be developed for each polypeptide, which is inconvenient and labor-intensive. Such challenges greatly burden the development of polypeptide formulations. SUMMARY The present disclosure provides, among other things, technologies (e.g., methods and compositions) for the administration (e.g., oral administration) of polypeptides, specifically including therapeutic polypeptides (e.g., antibody agents, enzymes, hormones, etc.). The present disclosure provides the surprising finding that certain formulations of polypeptides, e.g., specifically formulations of crystalline or amorphous polypeptides, can achieve effective systemic delivery of the polypeptides via oral administration of the formulations. Thus, the present disclosure provides, among other things, polypeptide formulations for oral delivery. In many embodiments, provided formulations comprise or otherwise utilize a polypeptide (e.g., a therapeutic polypeptide) in a crystalline (i.e., crystallized) or amorphous form. The present disclosure encompasses an insight that during a process of crystallizing a carrier polypeptide composition, an active polypeptide composition can be embedded in such carrier polypeptide composition, thereby creating a composition comprising both a carrier polypeptide composition and an active polypeptide composition. In some embodiments, a carrier polypeptide and an active polypeptide form a co-crystal during crystallization. In some embodiments, such composition comprising both a carrier polypeptide composition and an active polypeptide composition (e.g., a co-crystal of carrier polypeptide composition and an active polypeptide composition) is amenable for formulation. In some embodiments, conditions for crystallizing carrier polypeptide compositions can be used to embed a wide range of different active polypeptide compositions. Those skilled in the art will appreciate that methods and compositions provided by the present disclosure circumvent the need to develop crystallization methods for each active polypeptide composition and greatly improve the efficiency of developing polypeptide formulations. In many embodiments, the present disclosure provides oral formulations that comprise (1) a carrier polypeptide composition; (2) an active polypeptide composition; and optionally (3) a pharmaceutically acceptable carrier. In some embodiments, a carrier polypeptide composition co-exists with an active polypeptide composition. In some embodiments, an active polypeptide composition is embedded in a carrier polypeptide composition. In some embodiments, a carrier polypeptide composition is embedded in an active polypeptide composition. In some embodiments, a carrier polypeptide composition and an active polypeptide composition are each independently amorphous polypeptide composition or a crystallized polypeptide composition (e.g., a powder form that includes amorphous polypeptide or crystallized polypeptide). In some embodiments, a carrier polypeptide composition is an amorphous composition and an active polypeptide composition is a crystallized composition. In some embodiments, a carrier polypeptide composition is a crystallized composition and an active polypeptide composition is an amorphous composition. In some embodiments, a carrier polypeptide composition is a crystallized composition and an active polypeptide composition is crystallized composition. In some embodiments, a carrier polypeptide composition is an amorphous composition and an active polypeptide composition is an amorphous composition. In some embodiments, a carrier polypeptide composition and an active polypeptide composition form a co-crystal. In many embodiments, a carrier polypeptide composition and an active polypeptide composition of provided formulations each independently are or comprise a polypeptide (e.g., a therapeutic polypeptide) in a non-liquid phase—e.g., such formulations may be gels, solids, suspensions (e.g., of solid particles), etc. In some embodiments, a polypeptide formulation is or comprises a truffle formulation. In some embodiments, a truffle formulation comprises a pharmaceutically acceptable shell and a core that comprises (1) a carrier polypeptide composition and (2) an active polypeptide composition (e.g., a powder form that includes amorphous polypeptide or crystallized polypeptide); and (3) optionally a