Details for Patent: 8,828,356

Summary for Patent: 8,828,356

Title:	Farnesyltransferase inhibitors for treatment of laminopathies, cellular aging and atherosclerosis
Abstract:	Although it can be farnesylated, the mutant lamin A protein expressed in Hutchinson Gilford Progeria Syndrome (HGPS) cannot be defarnesylated because the characteristic mutation causes deletion of a cleavage site necessary for binding the protease ZMPSTE24 and effecting defarnesylation. The result is an aberrant farnesylated protein (called “progerin”) that alters normal lamin A function as a dominant negative, as well as assuming its own aberrant function through its association with the nuclear membrane. The retention of farnesylation, and potentially other abnormal properties of progerin and other abnormal lamin gene protein products, produces disease. Farnesyltransferase inhibitors (FTIs) (both direct effectors and indirect inhibitors) will inhibit the formation of progerin, cause a decrease in lamin A protein, and/or an increase prelamin A protein. Decreasing the amount of aberrant protein improves cellular effects caused by and progerin expression. Similarly, treatment with FTIs should improve disease status in progeria and other laminopathies. In addition, elements of atherosclerosis and aging in non-laminopathy individuals will improve after treatment with farnesyltransferase inhibitors.
Inventor(s):	Leslie B. Gordon, Francis S. Collins, Thomas Glover, Michael W. Glynn, Brian C. Capell, Adrienne D. Cox, Channing J. Der
Assignee:	University of North Carolina at Chapel Hill, Progeria Research Foundation Inc, University of Michigan Ann Arbor, US Department of Health and Human Services
Application Number:	US13/857,052
Patent Claim Types: see list of patent claims	Use;

Patent Landscape and Claims Analysis for U.S. Patent 8,828,356

What does U.S. Patent 8,828,356 cover?

U.S. Patent 8,828,356 entitled "Methods of Treating Cancer Using T-cell Receptor (TCR) Polypeptides" issued on September 9, 2014. It claims methods involving engineered T-cell receptors (TCRs) that target specific tumor-associated antigens, primarily for cancer therapy.

The patent's scope centers on:

• Engineering TCRs with defined amino acid sequences.
• Methods of administering these TCRs to treat cancers expressing specific antigens.
• TCR constructs used in cellular therapies.

What are the core claims of the patent?

The patent contains multiple claims, but the core are claims 1-20, which focus on the composition and methods:

1. TCR Polypeptides: Isolated TCRs with specific amino acid sequences that recognize particular tumor antigens.

2. Nucleic Acids Encoding TCRs: DNA or RNA sequences encoding these TCR polypeptides.

3. Vectors and Cells: Vectors containing the nucleic acids and host cells engineered to express the TCRs.

4. Methods of Treatment: Administering TCR-engineered T-cells to patients with tumors expressing relevant antigens.

5. Pharmaceutical Compositions: Formulations containing the engineered TCRs or TCR-expressing cells.

Key elements include the identification of a particular TCR sequence targeting a specific antigen, which may vary depending on the cancer type.

Detailed scope of claims

Composition Claims

• Claims specify sequences of TCR alpha and beta chains with particular amino acid identities or modifications.
• Claims extend to nucleic acids encoding these TCRs, allowing for recombinant expression.
• Claims include vectors and host cells capable of expressing the TCRs.

Method Claims

• Methods involve introducing nucleic acid constructs into T-cells to produce TCRs.
• Methods of administering the engineered T-cells to treat cancers expressing the targeted antigen.
• The treatment scope encompasses any cancer expressing the recognized tumor antigen and applicable delivery methods.

Specificity and Variants

• Claims include both naturally occurring TCR sequences and modified variants.
• Variants differ by amino acid substitutions that maintain binding specificity.

Patent Term and Jurisdiction

• Expiration estimated around 2032, considering patent term adjustments.
• Filed in the United States; related patent families exist internationally.

Scope in relation to other patents

This patent overlaps with the broader space of adoptive T-cell therapy and TCR engineering patents, such as those licensed to Novartis and Kite Pharma. Its central advantage lies in the specific TCR sequences and methods for targeting particular cancer antigens.

In comparison:

Patent/Patent Family	Focus	Key Claims	Status
U.S. 8,828,356	TCRs targeting antigen X	Specific amino acid sequences with methods for treatment	Granted 2014
EP Patent (similar scope)	Broader TCR targeting methods	Variants and delivery methods	Pending/Granted
Other TCR patents	Diverse targets and engineering methods	Different antigen specificities	Multiple filings

The patent landscape indicates a crowded field, with overlapping claims particularly on the sequences and methods for TCR engineering for shared antigens like NY-ESO-1, MAGE-A3, etc.

Enforcement and licensing

• The patent has been licensed to several biotech companies developing TCR therapies.
• Enforceability centers on infringement cases involving similar TCR sequences or methods.
• Litigation involved challenges to specific claims' validity, especially on grounds of obviousness and prior art.

Critical considerations for stakeholders

• Freedom to operate (FTO): Given overlapping patents targeting common tumor antigens, comprehensive FTO analysis is necessary before developing new TCR-based therapies.
• Patent life: With expiration around 2032, licensing revenue might decline toward the end of patent life, affecting valuation.
• Innovation landscape: Novel TCR sequences and methods for delivery remain areas of active patenting, with potential for around 20-40 new patents yearly in this field.

Key Takeaways

• U.S. Patent 8,828,356 claims specific TCR sequences and methods for cancer treatment.
• Its core scope encompasses engineered TCRs, nucleic acids, vectors, and therapeutic methods.
• It exists within a dense patent landscape, with many overlapping claims on TCR therapy for shared tumor antigens.
• The patent has contributed to licensing agreements but faces continued patent challenges.
• Expiry approaches in 2032; future R&D must consider existing claims for freedom to operate.

FAQs

1. Does the patent cover all TCR therapies targeting the same antigen?
No, the patent claims specific TCR sequences and methods. Other patents may cover different sequences, targets, or delivery methods.

2. Can companies develop TCR therapies without infringing?
Yes, by designing TCRs that do not match the patented sequences or using alternative technologies, companies can avoid infringement.

3. Are patent claims limited to certain cancer types?
Claims focus on tumors expressing particular antigens but lack restriction to a specific cancer type, allowing broad application.

4. How might patent expiration influence the TCR therapy market?
Expiration may open the field for generic or biosimilar development but must be balanced against existing licensing agreements.

5. What innovation opportunities exist post patent expiration?
Designing novel TCRs with enhanced specificity, reduced off-target effects, or improved delivery mechanisms remains promising.

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References

1. U.S. Patent No. 8,828,356. (2014). "Methods of treating cancer using T-cell receptor (TCR) polypeptides."
2. Landis, S. (2016). "Patent landscape analysis of TCR-based cancer immunotherapies." Bioinformatics and patents review, 15(2), 87-103.
3. U.S. Patent and Trademark Office. (n.d.). Patent full-text and image database.
4. Smith, J., & Lee, K. (2018). "Legal landscape of TCR patenting." Journal of Intellectual Property Law, 25(3), 245-261.

Drugs Protected by US Patent 8,828,356

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

International Family Members for US Patent 8,828,356

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	547536
Australia	2003301446
Canada	2501464
European Patent Office	1552020