US Patent 8,512,983: Claims, Patent Scope, Expiration, Litigation Risk and Bioprocessing Landscape

US Patent 8,512,983 protects production of recombinant polypeptides in mammalian cells using a glutamine-free culture medium containing 7.5 to 15 mM asparagine. The commercial value is concentrated in independent claims 1 and 25. Claim 1 covers a cell-culture process; claim 25 covers a ready-to-use medium. The patent is relevant to CHO-based manufacture of antibodies and other biologics, but it does not claim any particular drug molecule, antibody sequence, cell line, or downstream purification process.

The patent’s principal enforcement risk is process implementation. A biologics manufacturer may avoid infringement by using glutamine, using less than 7.5 mM or more than 15 mM asparagine, or conducting the relevant production phase under a materially different medium configuration. The patent is not an Orange Book drug patent and does not independently create a Paragraph IV pathway.

What does US Patent 8,512,983 claim?

The patent has two commercially important independent claims.

Claim	Claim type	Core limitation	Practical scope
1	Process	Culturing a mammalian host cell expressing a polypeptide in a glutamine-free production medium containing 7.5-15 mM asparagine	Direct coverage of a specified mammalian-cell production process
25	Composition	Ready-to-use glutamine-free cell-culture medium containing 7.5-15 mM asparagine for polypeptide production	Coverage of the production medium itself

Claims 2 through 24 depend from claim 1. They narrow the process through cell type, medium composition, production mode, product class, and therapeutic target.

What technical combination is required?

A process must generally satisfy all of the following conditions to fall within claim 1:

A mammalian host cell is used.
The cell expresses a polypeptide.
The cell is cultured during a production phase.
The production medium is glutamine-free.
The medium contains asparagine.
The asparagine concentration is 7.5 mM to 15 mM.

The claim does not require a specific antibody, promoter, vector, expression level, cell density, temperature, pH, osmolality, feed schedule, or purification method.

The concentration range is the central numerical limitation. Claim 2 narrows the range to 7.5 mM to 10 mM. A process using 7.49 mM asparagine would fall outside the literal range, subject to measurement, formulation, and equivalents issues. A process using 15.1 mM would likewise be outside the literal range, although prosecution history and the doctrine of equivalents could affect the analysis.

How do the dependent claims expand or narrow patent coverage?

Claims 3 through 12 address process architecture and culture conditions.

Claims	Limitation	Commercial significance
3-5	Eukaryotic, CHO, and dhfr-negative CHO cells	Targets conventional mammalian biologics manufacturing platforms
6	Serum-free medium	Covers the dominant commercial format for therapeutic biologics
7-8	Energy source, amino acids, vitamins, fatty acids, trace elements, hormones, salts, buffers, and nucleosides	Preserves broad medium-composition coverage
9	Batch or fed-batch production	Covers common industrial modes
10	Isolation of the polypeptide	Adds recovery of the product
11-12	Measurement of viability, longevity, productivity, or titer, with improvement relative to glutamine-containing medium	Introduces comparative performance limitations

Claims 13 through 24 cover the product being produced. They include mammalian glycoproteins, antibodies, antibody fragments, immunoadhesins, and a broad list of therapeutic proteins and antibody targets.

The target list includes HER2, CD20, VEGF, CD40, CD11a, CD18, IgE, EGFR, CD3, CD25, CD4, CD52, CD38, CD33, CD22, EpCAM, RSV, CMV, HIV, and other targets. Claims 19 through 22 specifically address antibodies binding HER receptors, VEGF, IgE, CD20, CD11a, CD40, BR3, or DR5, as well as BR3-Fc immunoadhesin products.

These product limitations do not convert the patent into a product patent. They remain dependent process claims. An antibody manufacturer must still practice the glutamine-free, asparagine-concentration, mammalian-cell process to infringe.

How strong are the independent claims?

Claim 1 has meaningful commercial breadth but several identifiable validity and infringement pressure points.

Claim 1 strengths

The claim focuses on a defined process window rather than a particular commercial molecule. That gives it potential application across multiple antibody and recombinant-protein programs. The claim also covers serum-free, batch, and fed-batch implementations through dependent claims that correspond to common manufacturing configurations.

The combination of glutamine omission and elevated asparagine concentration creates a narrower technical proposition than a generic claim to amino-acid supplementation. A prior-art reference would likely need to disclose, expressly or inherently, a glutamine-free mammalian production culture with asparagine in the claimed range.

Claim 1 weaknesses

The underlying concept may face obviousness challenges if the prior art taught glutamine-free media, asparagine supplementation, and optimization of amino-acid concentrations in mammalian cell culture. The numerical range may be attacked through routine optimization arguments, especially if prior references disclosed overlapping or adjacent concentrations.

The phrase “glutamine-free” may also create factual disputes. Commercial media can contain residual glutamine, glutamine substitutes, hydrolyzed components, or feed additions. The infringement analysis would depend on how the term is construed and whether glutamine is absent from the entire production phase or only from the initial medium.

“Production phase” is another operational limitation. A manufacturer could use glutamine during growth and remove it only during production, or use glutamine-free medium only in a later feed. Whether that falls within the claim depends on the claim construction of culturing “in a production phase” and the composition of the medium during that phase.

Claim 25 strengths and weaknesses

Claim 25 is directed to a ready-to-use medium rather than a complete manufacturing process. It does not recite a particular cell, polypeptide, culture vessel, or production result. That makes it potentially useful against suppliers and manufacturers that prepare or sell a qualifying medium.

Its principal weakness is the “for the production of a polypeptide in a production phase” language. The legal effect of that language may depend on whether it is treated as a functional limitation or an intended-use statement. A medium containing the required ingredients and concentration may be structurally identical to a medium sold for another purpose. The claim’s enforceability would turn on claim construction, product labeling, technical documentation, and actual use.

What patent protects the glutamine-free, asparagine-based process?

US Patent 8,512,983 is the key patent identified by the supplied claims. Its patent family and related applications should be reviewed for claim differentiation, prosecution amendments, terminal disclaimers, continuation rights, and any narrower issued claims.

Patent	Subject	Key independent subject matter	Issue date
US 8,512,983	Glutamine-free mammalian cell culture with asparagine	Process and ready-to-use medium	August 20, 2013

The patent was assigned to Genentech, Inc., based on the issued patent record. The claimed technology is platform manufacturing IP rather than molecule-specific IP. A company can therefore face exposure even when its product is not listed in the patent claims by name, provided its manufacturing process satisfies the limitations.

When does US Patent 8,512,983 lose exclusivity?

The patent’s expected nominal term runs to approximately December 2029, based on the earliest priority framework associated with the patent family and the standard 20-year term under 35 U.S.C. §154. The precise enforceable endpoint depends on the official USPTO term calculation, including any patent-term adjustment, terminal disclaimer, or other prosecution-specific adjustment.

Event	Date or status
Patent issued	August 20, 2013
Standard patent-term framework	20 years from the applicable earliest nonprovisional or international filing date
Expected nominal expiration	Approximately December 2029
Patent-term adjustment	Must be confirmed in the USPTO patent record
Patent-term extension under Hatch-Waxman	Generally not expected for this manufacturing-process patent
Regulatory exclusivity	Not created by this patent

Patent expiration does not eliminate trade-secret protection for manufacturing parameters that are not disclosed. It also does not invalidate separate patents covering cell lines, expression vectors, media feeds, purification systems, glycosylation control, or a biologic product.

What is the Orange Book status of US Patent 8,512,983?

US Patent 8,512,983 is not an Orange Book product patent or method-of-use listing for an approved drug. The FDA Orange Book primarily lists patents submitted by sponsors for approved drug products and certain approved methods of use. A general mammalian-cell manufacturing patent is not ordinarily listed against a specific small-molecule or biologic product in the Orange Book.[1]

The practical consequences are significant:

The patent does not automatically trigger an ANDA Paragraph IV certification.
It does not create a statutory 30-month stay under the Hatch-Waxman framework.
It is not equivalent to a patent claiming an antibody sequence, formulation, dosing regimen, or approved indication.
An ANDA applicant generally would not address this patent through the Orange Book certification process.

For biologics, the relevant framework is the Biologics Price Competition and Innovation Act. A biosimilar applicant’s manufacturing process can raise infringement issues under the BPCIA patent-disclosure and litigation framework, but the process patent is not an Orange Book-listed biologic patent.[2]

What Paragraph IV challenges or biosimilar risks exist?

No Paragraph IV challenge is inherently associated with this patent because the patent is not an Orange Book drug patent. A generic-drug applicant could still face ordinary patent litigation if its manufacturing activities infringe, but the challenge would not arise through a Paragraph IV certification to this patent.

Biosimilar exposure is more plausible. A biosimilar manufacturer using CHO cells and a glutamine-free production medium containing 7.5 to 15 mM asparagine could potentially practice claim 1. The risk would depend on:

Whether the production medium is genuinely glutamine-free.
Whether asparagine concentration remains within the claimed range after preparation and feeding.
Whether the process uses a mammalian host cell.
Whether production occurs in a batch or fed-batch phase.
Whether the relevant process is conducted in the United States.
Whether the patent remains enforceable when commercial manufacture begins.

The BPCIA allows biologic patent disputes to develop through the patent dance and subsequent litigation. A process patent may be relevant even where the biosimilar product itself is not claimed. The risk is strongest when the reference product manufacturer has access to process information through regulatory or commercial discovery mechanisms.

What patent litigation affects US Patent 8,512,983?

The supplied record does not establish a reported infringement judgment, settlement, or Paragraph IV proceeding directed specifically to US 8,512,983. The patent should therefore be treated as an issued process patent without a confirmed public litigation outcome in the materials provided.

A litigation assessment should distinguish three possible defendants:

A biologics manufacturer using the process internally.
A contract development and manufacturing organization supplying the process.
A media supplier selling a qualifying ready-to-use medium.

Claim 1 is most directly asserted against the manufacturer or CDMO. Claim 25 creates a possible theory against a medium supplier, although direct infringement would require proof that the supplied medium satisfies the claim and is intended or used for the claimed production purpose.

Potential remedies include an injunction, damages, and, in exceptional circumstances, enhanced damages. Indirect infringement would require proof of knowledge and the required relationship between the accused medium or instructions and the claimed process under 35 U.S.C. §§271(b) or 271(c).

What manufacturing and design-around options exist?

The patent leaves several practical design-around routes.

Design-around approach	Primary claim affected	Main technical issue
Use glutamine during production	Claim 1	Must avoid a glutamine-free production phase
Use asparagine below 7.5 mM	Claims 1, 2, 25	Must validate productivity and cell viability
Use asparagine above 15 mM	Claims 1, 25	May affect osmolality, growth, and product quality
Use a non-mammalian host	Claim 1 and dependents	May require a different expression platform
Keep asparagine outside the claimed range during production	All key claims	Feed strategy and analytical records become important
Use an alternative nitrogen or amino-acid strategy	Process claims	Must avoid literal and equivalents-based overlap
Perform manufacturing outside the United States	US claims	US importation and domestic commercial activities remain relevant

A design-around based solely on nominal concentration is vulnerable if the process uses multiple feeds that cumulatively create a claimed concentration during production. Batch records, medium certificates, feed maps, and in-process analytical data would be central evidence.

How does this patent compare with conventional biologics patent estates?

US 8,512,983 is narrower in subject matter but potentially broader in product reach than a molecule-specific patent.

Patent category	Typical claim focus	Relationship to US 8,512,983
Composition-of-matter patent	Antibody or protein sequence	Usually stronger against the molecule, independent of manufacturing medium
Formulation patent	Stabilizers, buffers, concentration, container	Covers the finished drug product, not necessarily upstream culture
Method-of-use patent	Dosing or indication	Relevant to clinical use and labeling
Cell-line patent	Host cell or engineered phenotype	May overlap with CHO production platforms
Process patent	Culture, feed, temperature, pH, media	Closest category to US 8,512,983
Purification patent	Chromatography or viral clearance	Applies downstream of cell culture
US 8,512,983	Glutamine-free medium with 7.5-15 mM asparagine	Upstream production-process coverage

A commercial biologic may therefore require a freedom-to-operate review across several patent layers. Expiration of this patent would not clear the product from sequence, formulation, use, purification, or cell-line patents.

What is the commercial exposure?

The patent does not identify a specific approved product or revenue stream. Its exposure is platform-based. The highest-value targets are therapeutic antibodies and other high-volume recombinant proteins produced in CHO cells, particularly where the manufacturer uses chemically defined, serum-free, fed-batch processes.

Revenue risk depends on whether the claimed medium is used in:

Commercial production batches.
Process-development runs that support US manufacture.
Clinical-supply manufacturing.
Contract manufacturing performed for multiple sponsors.
Biosimilar production intended for US launch.

The patent is less likely to block a product entirely than to require process modification, licensing, or a litigation-risk reserve. Because the claims do not require a specific therapeutic molecule, a successful assertion could affect several programs using the same platform process.

Key Takeaways

US Patent 8,512,983 is a platform manufacturing patent, not a product or Orange Book drug patent.
Claim 1 requires mammalian-cell production in glutamine-free medium containing 7.5 to 15 mM asparagine.
Claim 25 separately covers a ready-to-use medium with the same core concentration range.
CHO, dhfr-negative CHO, serum-free, batch, and fed-batch embodiments are expressly covered by dependent claims.
The patent does not create a Paragraph IV certification obligation.
Biosimilar and CDMO exposure is more relevant than conventional generic-drug exposure.
The expected nominal expiration is approximately December 2029, subject to the official USPTO term calculation.
The strongest design-arounds are glutamine inclusion, an asparagine concentration outside the claimed range, or a non-mammalian production platform.
No confirmed litigation, settlement, or licensing outcome is established by the supplied record.
Freedom-to-operate analysis must include separate patents covering molecules, formulations, cell lines, purification, and therapeutic use.

FAQs

Can a manufacturer use 7.5 mM asparagine without infringing?

No categorical answer follows from the concentration alone. Exactly 7.5 mM is within the literal range stated in claims 1, 2, and 25. Measurement methodology and the composition of the production phase would also matter.

Does using glutamine only during the growth phase avoid claim 1?

Possibly, but the analysis depends on whether the production phase itself is glutamine-free and whether residual glutamine or a glutamine-containing feed remains present during that phase.

Does the patent cover a specific antibody such as trastuzumab?

No. The patent covers a process for producing polypeptides. It does not claim trastuzumab, another antibody sequence, or a particular approved antibody product as such.

Can a media supplier be sued under claim 25?

Potentially. Claim 25 is directed to a ready-to-use medium. Liability would depend on the medium’s composition, its production-purpose labeling or instructions, the supplier’s knowledge, and the required direct or indirect infringement theory.

Does patent expiration eliminate all US manufacturing risk?

No. Expiration would remove this patent’s enforceable exclusionary rights, but separate patents covering the biologic, cell line, formulation, purification process, or method of treatment may remain active.

References

U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services.
Biologics Price Competition and Innovation Act, Pub. L. No. 111-148, §§7001-7003, 124 Stat. 119, 804-821 (2010).
United States Patent No. 8,512,983. (2013). Methods for producing polypeptides using glutamine-free cell culture media. U.S. Patent and Trademark Office.
35 U.S.C. §§154, 271, 282 (2024).
U.S. Patent and Trademark Office. (2024). Patent Center. U.S. Department of Commerce.

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Microbix Biosystems Inc.	KINLYTIC	urokinase	For Injection	021846	January 16, 1978	8,512,983	2030-08-06
Grifols Therapeutics Llc	ALBUKED, PLASBUMIN-20, PLASBUMIN-25, PLASBUMIN-5	albumin (human)	For Injection	101138	October 21, 1942	8,512,983	2030-08-06
Takeda Pharmaceuticals U.s.a., Inc.	BUMINATE, FLEXBUMIN	albumin (human)	Injection	101452	March 3, 1954	8,512,983	2030-08-06
Csl Behring Ag	ALBURX	albumin (human)	Injection	102366	July 23, 1976	8,512,983	2030-08-06
>Applicant	>Tradename	>Biologic Ingredient	>Dosage Form	>BLA	>Approval Date	>Patent No.	>Expiredate

Country	Patent Number	Estimated Expiration
Australia	2010282733	⤷ Start Trial
Australia	2016238859	⤷ Start Trial
Australia	2019201603	⤷ Start Trial
Brazil	112012002974	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration

Patent: 8,512,983

Summary for Patent: 8,512,983