The purpose of this column is to highlight and summarize recent key patents in the pharmaceutical arena issued by the US Patent Office in August–September 2021.
Hemant N. Joshi, Ph.D., MBA* Tara Innovations, LLC www.tarainovations.com and www.tara-marketing.com *[email protected]
Drug Delivery Device Having Controlled Delivery and Confirmation
N.C. Codella, J. H. Connell II, S. Pankanti, and N.K. Ratha; IBM Corp., Armont, USA; US Patent # 11,052,023; July 6, 2021.
Healthcare providers often can’t know for certain if patients have faithfully taken medication at proper intervals and with the correct doses. Healthcare professionals also can’t be present to prevent accidental overdose or to ensure that the correct medication is administered. The patent describes a capsule as the drug delivery device, which contains a logic circuit disposed within the capsule, and an actuator connected to the logic circuit and configured to expose an interior of the capsule to an exterior of the capsule upon activation by the logic circuit. The capsule contains desired active and inactive components. The external computer can provide various sets of commands to the capsule.
Shear-Thinning Self-Healing Networks
E.A. Appel, M.W. Tibbitt, and R.S. Langer; MIT, Cambridge, USA; US Patent #11,045,429; June 29, 2021.
Gels have been getting popular in pharmaceutical formulations. Many gels utilize a covalent cross-linking approach to form robust and tough materials but suffer from limited irreversibility. The patent describes rationally designed gels with non-covalent interactions that provide reversible control over the self-assembly process. These gels demonstrate shear-thinning under stress and fast self-healing when the stress is removed. It describes the process to prepare polymer-nanoparticle gels. The polymer selectively adsorbs to nanoparticles to form non-covalent cross-links, yielding a gel structure. The hydrogel optionally comprises one or more therapeutic, prophylactic or diagnostic agents encapsulated within the nanoparticles.
Hepatitis B Virus (HBV) iRNA Compositions and Methods of Use Thereof
G. Hinkle, L. Sepp-Lorenzino, M. Maier, S. Milstein, M. Manoharan, and R.G. Rajeev; Alnylam Pharm. Cambridge, USA; US Patent # 11,060,091; July 13, 2021.
The natural evolution of chronic HBV infection includes four consecutive phases: (1) early `immunotolerant` phase, high levels of virus replication and minimal liver inflammation; (2) immune reactive phase, significant hepatic inflammation and elevated serum aminotransferases; with some patients progressing to (3) `non- replicative` phase, seroconversion to anti-HBe; undetectable or low level of viremia; resolution of hepatic inflammation; and (4) HBeAg- negative chronic hepatitis B, due to the emergence of specific viral mutations, which prevent the production of HBeAg but do not hamper virus replication. The primary goal of treatment for HBV is to permanently suppress HBV replication and improve liver disease. The present invention relates to double-stranded iRNA agents targeting the hepatitis B virus (HBV) genome, and inhibiting expression of one or more HBV genes.
Stable Protein Formulations Comprising a Molar Excess of Sorbitol
K. Chandrmouli and R. Pai; Biocon Ltd., Banglore, India and Mylan GMBH, Zurich, CH; US Patent # 11,058,768; July 13, 2021.
Proteins are complex molecules with defined primary, secondary, tertiary and in some cases quaternary structures, all of which play a role in imparting specific biological function. Formulators need to assure both chemical and physical stability of a protein molecule. Many excipients are used to stabilize protein molecules and these prevent denaturation, aggregation etc. This patent describes a stable formulation of anti-HER2 antibody including a sugar alcohol (sorbitol), a histidine buffer, and polyethylene glycol. The pH of the formulation is maintained between 5.0 and 7.5 and the product can be lyophilized or can be stored in a liquid form. The sorbitol and the anti-HER2 antibody are present in a molar ratio of 550 to 700 moles of sorbitol:1 mole of the anti-HER2 antibody; wherein the PEG is present in a molar ratio of 5 to 15 moles PEG:1 mole of the anti-HER2 antibody.
Solid Drug Tablets for Implantable Drug Delivery Devices
K.D. Daniel, B.M. Hutchins III, C. Larrivee- Elkins, and H. Lee; Taris Biomedical LLC, MA, USA; US. Patent # 11,040,005; June 22, 2021.
Conventional tablets or capsules are intended for oral administration and for the systemic delivery of drugs. Very rarely, tablets are used for local delivery of drugs. The tablet in this patent contains a local anesthetic agent and is mainly intended for delivery to the bladder. The tablets are more cylindrical in shape and are mini-tablets. They contain more than 50% actives. The patent also describes a plurality of tablets filled in a medical device so as to allow an insertion through urethra of a patient into the bladder. Multiple tablets can be inserted into the bladder or into the body cavity. The minitablets can be sterilized too. One can insert other types of drugs using this technique in various body cavities.
Concentrated, Inhalable Ciprofloxacin Formulation
D.C. Cipolla and J. Blanchard; Gripols S.A., CA, USA; US Patent # 11,026,941; June 8, 2021.
Ciprofloxacin is a fluoroquinolone antibiotic that is indicated for the treatment of lower respiratory tract infections due to P. aeruginosa, which is common in patients with cystic fibrosis. Ciprofloxacin produces bothersome side effects, such as GI intolerance, dizziness, insomnia, irritability and increased levels of anxiety. Delivery to the respiratory tract in an aerosolized form can reduce such side-effects. The tissue distribution of ciprofloxacin is so rapid that the drug residence time in the lung is too short to provide additional therapeutic benefit over drug administered by oral or IV routes. The patent describes a formulation containing free unencapsulated ciprofloxacin; a pharmaceutically acceptable excipient; and liposome-encapsulated ciprofloxacin with an average particle size of 1 nm to 10 microns, and provides a ciprofloxacin release rate of 0.5% to 20% per hour over a period of time of 1-12 hours.
Parenteral Formulations of Lipophilic Pharmaceutical Agents and Methods for Preparing and Using the Same
B.S. Andersson, B.C. Valdez, J. Tarrand; Platform Brightworks Two, Ltd. TX, USA; US Patent # 11,045,466; June 29, 2021.
Busulfan is 1,4-butanediol dimethane sulfonate. It is used as an adjunct therapy with cyclophosphamide for conditioning prior to bone marrow transplantation in adults and children. The patent presents a homogeneous, non-aqueous pharmaceutically acceptable solution comprising busulfan solubilized in a non-aqueous polyethylene glycol (PEG). The solution remains stable and free of non-solubilized pharmaceutical particles for at least 40 days at room temperature. In the current commercial product, each vial contains 60 mg of busulfan in N,N- dimethylacetamide (DMA), 3.3 mL and polyethylene Glycol, NF 6.7 mL. DMA is a potentially toxic solvent and therefore, the currently patented formulation may have an advantage.
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