# US 2021/0330801 A1 · Novel protein drug conjugate formulation > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2021/0330801 A1 - Document ID: US20210330801A1 - Status: Published application - Kind: A1 - Application number: 16/490,208 - Filed: 2018-03-01 - Published: 2021-10-28 - Earliest claimed: 2017-03-02 - Assignees: Cadila Healthcare Limited - Applicants: Cadila Healthcare Limited - Inventors: Sanjeev Kumar MENDIRATTA; Sanjay BANDYOPADHYAY; Avanish Kumar SINGH; Chintan PATEL - Web page: https://patentgrep.com/patent/US20210330801A1 ## CPC - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61K 9/19: lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)} - A61K 39/39591: {Stabilisation, fragmentation} - A61K 47/02: Inorganic compounds - A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin - A61K 47/68033: {the drug being a maytansine} - A61K 47/6855: {the tumour determinant being from breast cancer cell} - C07K 16/32: against translation products of oncogenes - C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) ## Abstract The invention provides stable pharmaceutical formulation comprising a protein drug conjugate along with one or more suitable excipient(s) such that the formulation is devoid of any buffer components and methods of making the same. The protein drug conjugate according to the present invention is antibody drug conjugate, preferably trastuzumab maytansinoid conjugate. Suitable excipient(s) according to the present invention is selected from suitable bulking agents, suitable tonicity modifiers, suitable stabilizers and the like. ## Claims ### Claim 1 An aqueous pharmaceutical formulation comprising essentially of : a. Trastuzumab maytansinoid conjugate and b. Water. ### Claim 2 An aqueous pharmaceutical formulation comprising: a. Trastuzumab maytansinoid conjugate; and b. water; wherein the formulation does not contain buffering agent. ### Claim 3 (depends on 2) The aqueous pharmaceutical formulation as claimed in claim 2 which further comprises one or more non-ionizable excipients. ### Claim 4 (depends on 3) The aqueous pharmaceutical formulation as claimed in claim 3, wherein the non-ionizable excipient is selected from sugar alcohol, polyol, a non-ionic surfactant, sugar and suitable combination thereof. ### Claim 5 (depends on 4) The aqueous pharmaceutical formulation as claimed in claim 4, wherein polyol is selected from mannitol or sorbitol. ### Claim 6 (depends on 4) The aqueous pharmaceutical formulation as claimed in claim 4, wherein the non-ionic surfactant is selected from polysorbate 80, polysorbate 20, polysorbate 40, polysorbate 60. ### Claim 7 (depends on 4) The aqueous pharmaceutical formulation as claimed in claim 4, wherein sugar is selected from sucrose, trehalose, raffinose and maltose. ### Claim 8 (depends on 2) The aqueous pharmaceutical formulation as claimed in claim 2 which further comprises one or more tonicity modifiers. ### Claim 9 (depends on 8) The aqueous pharmaceutical formulation as claimed in claim 8, wherein tonicity modifier is selected from sodium chloride, potassium chloride, potassium sulfate and sodium sulfate. ### Claim 10 (depends on 2) The aqueous pharmaceutical formulation as claimed in claim 2 wherein the pH of the formulation is between pH 4 to pH 8. ### Claim 11 (depends on 1) The aqueous pharmaceutical formulation as claimed in claim 1 2 having a shelf life of 1 to 5 years, when stored between 2-8° C. ### Claim 12 (depends on 2) The aqueous pharmaceutical formulation as claimed in claim 2 which is stable for at least one freeze/thaw cycle. ### Claim 13 (depends on 2) The aqueous pharmaceutical formulation as claimed in claim 2 which maintains stability during long-term liquid storage or during carrying out of other processing steps selected from freeze/thaw and lyophilization. ### Claim 14 (depends on 2) The aqueous pharmaceutical formulation as claimed in claim 2 which is suitable for administration to a subject via a mode of administration including subcutaneous, intravenous, intradermal, transdermal, intraperitoneal and intramuscular administration. ### Claim 15 (depends on 2) A lyophilized formulation comprising the composition as claimed in claim 2. ### Claim 16 (depends on 2) A method of preparing formulation of trastuzumab maytansinoid conjugate as claimed in claim 2 comprising; a. Providing the Trastuzumab maytansinoid conjugate in a first solution; b. Subjecting the first solution to diafiltration using diafiltration medium till suitable amount of exchange with diafiltration medium has been achieved to obtain diafiltered Trastuzumab maytansinoid conjugate solution, wherein diafiltration medium is a buffer or water. ### Claim 17 (depends on 16) The method of preparing formulation of trastuzumab maytansinoid conjugate as claimed in claim 16 wherein diafiltration medium is water. ### Claim 18 (depends on 16) The method of preparing formulation of trastuzumab maytansinoid conjugate as claimed in claim 16 wherein the diafiltered Trastuzumab maytansinoid conjugate solution is achieved via ultrafiltration diafiltration. ### Claim 19 (depends on 2) The pharmaceutical formulation of trastuzumab maytansinoid conjugate as claimed in claim 2, wherein trastuzumab maytansinoid conjugate is T-DM1. ### Claim 20 (depends on 1) A lyophilized formulation comprising the composition as claimed in claim 1.