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- Nachgewiesen in: USPTO Patent Applications
- Sprachen: English
- Document Number: 20220118053
- Publication Date: April 21, 2022
- Appl. No: 17/428604
- Application Filed: February 10, 2020
- Claim: 1. A dry pharmaceutical formulation, wherein the pharmaceutical formulation comprises a CNP conjugate, a buffering agent and a bulking agent and wherein the CNP conjugate comprises a CNP moiety that is covalently and reversibly conjugated to a polymeric moiety.
- Claim: 2. The dry pharmaceutical formulation of claim 1, wherein the buffering agent is selected from the group consisting of succinic acid, citric acid, lactic acid, acetic acid, glutamic acid, fumaric acid, aspartic acid, glutaric acid, phosphoric acid, histidine, gluconic acid, tartaric acid, malic acid and mixtures thereof.
- Claim: 3. The dry pharmaceutical formulation of claim 1, wherein the buffering agent is succinic acid.
- Claim: 4. The dry pharmaceutical formulation of claim 1, wherein the bulking agent is selected from the group consisting of trehalose, mannitol, sucrose, raffinose, gelatin, lactose, dibasic calcium phosphate, sorbitol, xylitol, glycine, histidine, hydroxy ethyl starch, dextrose, dextran, propylene glycol and mixtures thereof.
- Claim: 5. The dry pharmaceutical formulation of claim 1, wherein the bulking agent is selected from the group consisting of trehalose, sucrose and glycine.
- Claim: 6. The dry pharmaceutical formulation of claim 1, wherein the bulking agent is trehalose.
- Claim: 7. The dry pharmaceutical formulation of claim 1, wherein the dry pharmaceutical formulation comprises one or more further excipients.
- Claim: 8. The dry pharmaceutical formulation of claim 7, wherein the one or more further excipients are selected from the group consisting of a preservative, stabilizer, anti-adsorption agent, cryoprotectant, oxidation protection agent and other auxiliary agents.
- Claim: 9. The dry pharmaceutical formulation of claim 1, wherein the dry pharmaceutical formulation comprises a stabilizer.
- Claim: 10. The dry pharmaceutical formulation of claim 1, wherein the dry pharmaceutical formulation comprises a preservative.
- Claim: 11. The dry pharmaceutical formulation of claim 1, wherein the dry pharmaceutical formulation comprises an anti-absorption agent.
- Claim: 12. The dry pharmaceutical formulation of claim 1, wherein the dry pharmaceutical formulation comprises a cryoprotectant.
- Claim: 13. The dry pharmaceutical formulation of claim 1, wherein the dry pharmaceutical formulation comprises an oxidation protection agent.
- Claim: 14. The dry pharmaceutical formulation of claim 1, wherein the dry pharmaceutical formulation comprises a further excipient selected from the group consisting of wetting agents, viscosity modifiers and antibiotics.
- Claim: 15. The dry pharmaceutical formulation of claim 1, wherein the pharmaceutical formulation comprises a pH-adjusting agent.
- Claim: 16. The dry pharmaceutical formulation of claim 15, wherein the pH-adjusting agent is selected from the group consisting of Tris, sodium hydroxide, potassium hydroxide, lysine and mixtures thereof.
- Claim: 17. The dry pharmaceutical formulation of claim 15, wherein the pH-adjusting agent is Tris.
- Claim: 18. The dry pharmaceutical formulation of claim 1, wherein the pharmaceutical formulation comprises a CNP conjugate, succinic acid, trehalose and Tris.
- Claim: 19. The dry pharmaceutical formulation of claim 1, wherein the CNP moiety has the sequence of SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25 or SEQ ID NO:30.
- Claim: 20. The dry pharmaceutical formulation of claim 1, wherein the CNP moiety has the sequence of SEQ ID NO:24.
- Claim: 21. The dry pharmaceutical formulation of claim 1, wherein the polymeric moiety comprises a polymer selected from the group consisting of 2-methacryloyl-oxyethyl phosphoyl cholins, poly(acrylic acids), poly(acrylates), poly(acrylamides), poly(alkyloxy) polymers, poly(amides), poly(amidoamines), poly(amino acids), poly(anhydrides), poly(aspartamides), poly(butyric acids), poly(glycolic acids), polybutylene terephthalates, poly(caprolactones), poly(carbonates), poly(cyanoacrylates), poly(dimethylacrylamides), poly(esters), poly(ethylenes), poly(ethyleneglycols), polyethylene oxides), poly(ethyl phosphates), poly(ethyloxazolines), poly(glycolic acids), poly(hydroxyethyl acrylates), poly(hydroxyethyl-oxazolines), poly(hydroxymethacrylates), poly(hydroxypropylmethacrylamides), poly(hydroxypropyl methacrylates), poly(hydroxypropyloxazolines), poly(iminocarbonates), poly(lactic acids), poly(lactic-co-glycolic acids), poly(methacrylamides), poly(methacrylates), poly(methyloxazolines), poly(organophosphazenes), poly(ortho esters), poly(oxazolines), poly(propylene glycols), poly(siloxanes), poly(urethanes), poly(vinyl alcohols), poly(vinyl amines), poly(vinylmethylethers), poly(vinylpyrrolidones), silicones, celluloses, carbomethyl celluloses, hydroxypropyl methylcelluloses, chitins, chitosans, dextrans, dextrins, gelatins, hyaluronic acids and derivatives, functionalized hyaluronic acids, mannans, pectins, rhamnogalacturonans, starches, hydroxyalkyl starches, hydroxyethyl starches and other carbohydrate-based polymers, xylans, and copolymers thereof.
- Claim: 22. The dry pharmaceutical formulation of claim 1, wherein the formulation comprises based on the total weight of the dry pharmaceutical formulation: [table included]
- Claim: 23. The dry pharmaceutical formulation of claim 1, wherein the formulation comprises based on the total weight of the dry pharmaceutical formulation: [table included]
- Claim: 24. The dry pharmaceutical formulation of claim 1, wherein the CNP conjugate is formula (Ia) or (Ib): ZL2-L1-D)x (Ia), DL1-L2-Z)y (Ib), wherein -D is a CNP moiety; -L1- is a reversible linker moiety; -L2- is a single chemical bond or a spacer moiety; —Z is a polymeric moiety; x is an integer selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and 16; and y is an integer selected from the group consisting of 1, 2, 3, 4 and 5.
- Claim: 25. The dry pharmaceutical formulation of claim 24, wherein x of formula (Ia) is an integer selected from the group consisting of 1, 2, 3, 4, 6 and 8.
- Claim: 26. The dry pharmaceutical formulation of claim 24, wherein y of formula (Ib) is an integer selected from the group consisting of 2, 3, 4 and 5.
- Claim: 27. The dry pharmaceutical formulation of claim 24, wherein the CNP conjugate is of formula (Ia) and x is 1.
- Claim: 28. The dry pharmaceutical formulation of claim 24, wherein -L1- is connected to -D through an amide linkage.
- Claim: 29. The dry pharmaceutical formulation of claim 24, wherein the linkage between —Z and -L2- is a stable linkage.
- Claim: 30. The dry pharmaceutical formulation of claim 24, wherein -L2- is a spacer moiety.
- Claim: 31. The dry pharmaceutical formulation of claim 24, wherein -L2- has a molecular weight in the range of from 14 g/mol to 750 g/mol.
- Claim: 32. The dry pharmaceutical formulation of claim 24, wherein -L2- has a chain length of 1 to 20 atoms.
- Claim: 33. The dry pharmaceutical formulation of claim 24, wherein -L2- is of formula (i): [chemical expression included] wherein the dashed line marked with the asterisk indicates attachment to -L1-; the unmarked dashed line indicates attachment to —Z; —R1 is selected from the group consisting of —H, C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl; n is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 and 18; and wherein the moiety of formula (i) is optionally further substituted.
- Claim: 34. The dry pharmaceutical formulation of claim 33, wherein n of formula (i) is selected from the group consisting of 3, 4, 5, 6, 7, 8 and 9.
- Claim: 35. The dry pharmaceutical formulation of claim 24, wherein —Z has a molecular weight ranging from 5 to 200 kDa.
- Claim: 36. The dry pharmaceutical formulation of claim 24, wherein —Z comprises a polymer selected from the group consisting of 2-methacryloyl-oxyethyl phosphoyl cholins, poly(acrylic acids), poly(acrylates), poly(acrylamides), poly(alkyloxy) polymers, poly(amides), poly(amidoamines), poly(amino acids), poly(anhydrides), poly(aspartamides), poly(butyric acids), poly(glycolic acids), polybutylene terephthalates, poly(caprolactones), poly(carbonates), poly(cyanoacrylates), poly(dimethylacrylamides), poly(esters), poly(ethylenes), poly(ethyleneglycols), polyethylene oxides), poly(ethyl phosphates), poly(ethyloxazolines), poly(glycolic acids), poly(hydroxyethyl acrylates), poly(hydroxyethyl-oxazolines), poly(hydroxymethacrylates), poly(hydroxypropylmethacrylamides), poly(hydroxypropyl methacrylates), poly(hydroxypropyloxazolines), poly(iminocarbonates), poly(lactic acids), poly(lactic-co-glycolic acids), poly(methacrylamides), poly(methacrylates), poly(methyloxazolines), poly(organophosphazenes), poly(ortho esters), poly(oxazolines), polypropylene glycols), poly(siloxanes), poly(urethanes), poly(vinyl alcohols), poly(vinyl amines), poly(vinylmethylethers), poly(vinylpyrrolidones), silicones, celluloses, carbomethyl celluloses, hydroxypropyl methylcelluloses, chitins, chitosans, dextrans, dextrins, gelatins, hyaluronic acids and derivatives, functionalized hyaluronic acids, mannans, pectins, rhamnogalacturonans, starches, hydroxyalkyl starches, hydroxyethyl starches and other carbohydrate-based polymers, xylans, and copolymers thereof.
- Claim: 37. A method of manufacturing the dry pharmaceutical formulation of claim 1, wherein the method comprises the steps of (i) admixing the CNP conjugate with at least a buffering agent and a bulking agent; (ii) adjusting the pH of the admixture of step (i); (iii) optionally, filtering the admixture from step (ii); (iv) transferring amounts of the admixture from step (ii) or (iii) equivalent to the desired number of dosages into a container; (v) drying the admixture; (vi) sealing the container; and wherein the order of steps (ii) and (iii) may optionally be reversed.
- Claim: 38. A method of reconstituting the dry pharmaceutical formulation of claim 1, wherein the method comprises the step of (a) contacting the dry pharmaceutical formulation of claim 1, with a reconstitution solution.
- Claim: 39. A reconstituted pharmaceutical formulation obtainable from the method of reconstituting of claim 38.
- Claim: 40-43. (canceled)
- Claim: 44. A method of treating, controlling, delaying or preventing in a patient one or more diseases which can be treated by CNP, the method comprising administering to the patient a therapeutically effective amount of the reconstitution pharmaceutical formulation of claim 39.
- Claim: 45. The method of claim 44, wherein the disease is selected from the group consisting of bone-related disorders such as skeletal dysplasias; cancer; autoimmune diseases; fibrotic diseases; inflammatory diseases; central nervous system diseases such as neurodegenerative diseases; infectious diseases; lung diseases; heart and vascular diseases; metabolic diseases and ophthalmic diseases.
- Claim: 46. The method of claim 44, wherein the disease is achondroplasia.
- Claim: 47. The dry pharmaceutical formulation of claim 1, wherein the pharmaceutical formulation comprises a mixture of one or more acid and based pH-adjusting agents.
- Claim: 48. The dry pharmaceutical formulation of claim 25, wherein -D of formula (Ia) or (Ib) has the sequence of SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25 or SEQ ID NO:30.
- Claim: 49. The dry formulation of claim 25, wherein -D of formula (Ia) or (Ib) has the sequence of SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24 or SEQ ID NO:25.
- Current International Class: 61; 61; 61; 61; 61; 61; 61
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