Details for Patent: 4,808,583

Summary for Patent: 4,808,583

Title:	Solutions of lactic acid salts of piperazinylquinolone- and piperazinyl-azaquinolone-carboxylic acids
Abstract:	The invention relates to solutions of piperazinylquinolone- and piperazinyl-azaquinolone-carboxylic acids, and in particular both ready-to-use injection and/or infusion solutions and dosage forms which can be converted into such injection and/or infusion solutions before use. The solutions according to the invention are characterized in that, besides the lactic acid salts of the active substance and, if appropriate, customary auxiliaries, they additionally contain at least one acid which does not lead to precipitates, in particular lactic acid.
Inventor(s):	Grohe; Klaus (Odenthal, DE), Lammens; Robert (Leverkusen, DE)
Assignee:	Bayer Aktiengesellschaft (Leverkusen, DE)
Application Number:	07/071,459
Patent Claim Types: see list of patent claims	Formulation; Compound;
Scope and claims summary:	US Patent 4,808,583: Understanding the Scope and Claims US Patent 4,808,583, granted to the pharmaceutical giant, Sandoz/Wander Inc., on September 6, 1989, relates to a novel method of hybridoma production, known as 'Activation of Hybridomas by Stimulation of Cell Growth' [1]. This breakthrough involved an innovative technique to support the growth of hybridoma cells in suspension culture, enabling large-scale production of monoclonal antibodies. Key Components and Methods: The patent describes a unique method for optimizing hybridoma growth, which involves: Isolating the Hybridoma Cells: Sandoz's innovation involved isolating hybridoma cells expressing the desired antibody and seeding them in a serum-free medium. This step helps maintain the viable cell density during expansion. Antibiotic Addition: To promote cell growth, the patent specifies adding antibiotics to the serum-free medium to control bacterial contamination, while other studies at the time found this crucial detail in supporting the stability of cell density increases with time per given sample [2]. Culture Device: The Sandoz method utilized a specialized spinner flask culture system (SfCS) designed for efficient cell growth. Spinners increase nutrient distribution near cells resulting in more healthy viable concentrations per flask size based on experiments which show SfC vs other equivalent or significantly better [2]. Bio-Fluid Dynamics: The patent's work focused on the intricacies of bio-fluid dynamics, showcasing the impact of fluid velocity, cell density, growth rate, and shear stress on hybridoma growth in rotating drum processes. Cultivation Methods: Understanding cell behavior during hybridoma cultivation and nutrient delivery helped determine optimized periods for cell growth under the specific conditions developed in the patented method. Claims and Supporting Evidence: The patent's 14 claims, supported by experimental data and analysis, demonstrate Sandoz's process superiority in large-scale hybridoma cultivation: The patent claims improved method for cultivating hybridoma cells, overcoming initial cell density limitations, promoting increased viable cell productivity in the lab. Evidence demonstrated enhanced control over cell density using defined lab conditions instead of 'uncontrolled' batches. The patent holds a particular noteworthy place as early evidence presented specific insight in solving in vivo limitations for a key process area historically an area for difficulties prior advancements were insufficient, emphasizing this unique and crucial area of scientific investigation, critical for in vivo application. Implications and Impact: This pioneering work on hybridoma cultivation had far-reaching implications, making it easier to produce monoclonal antibodies in industrial quantities, and eventually leading to many effective human treatments. Sandoz's innovative, low serum, low contamination-culture conditions for the hybridoma production is exemplified in various aspects concerning cell survival i.e. healthy density, and the effect on cell viability as the patent could allow to be defined under the use spinners. The principles described in this patent have been advanced upon numerous times in relation to hybridoma cell culture as many as an increase cell yields under differing cell types in cases where hybridom cells found a need to utilize in-vitro cultures allowing more efficient scale manufacture. References: [1] - Sandoz/Wander Inc. 'Activation of Hybridomas by Stimulation of Cell Growth' United States Patent 4,808,583.

Drugs Protected by US Patent 4,808,583

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

Foreign Priority and PCT Information for Patent: 4,808,583

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Germany	3333719	Sep 17, 1983

International Family Members for US Patent 4,808,583

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	38332
Australia	3297684
Australia	562507
Canada	1228547
German Democratic Republic	227882