Details for Patent: 5,922,695

Summary for Patent: 5,922,695

Title:	Antiviral phosphonomethyoxy nucleotide analogs having increased oral bioavarilability
Abstract:	Novel compounds are provided that comprise esters of antiviral phosphonomethoxy nucleotide analogs with carbonates and/or carbamates having the structure --OC(R2)2 OC(O)X(R)a, wherein R2 independently is H, C1 -C12 alkyl, aryl, alkenyl, alkynyl, alkyenylaryl, alkynylaryl, alkaryl, arylalkynyl, arylalkenyl or arylalkyl which is unsubstituted or is substituted with halo, azido, nitro or OR3 in which R3 is C1 -C12 alkyl; X is N or O; R is independently H, C1 -C12 alkyl, aryl, alkenyl, alkynyl, alkyenylaryl, alkynylaryl, alkaryl, arylalkynyl, arylalkenyl or arylalkyl which is unsubstituted or is substituted with halo, azido, nitro, --O--, --N═, --NR4 --, --N(R4)2 -- or OR3, R4 independently is --H or C1 -C8 alkyl, provided that at least one R is not H; and a is 1 or 2, with the proviso that when a is 2 and X is N, (a) two R groups can be taken together to form a carbocycle or oxygen-containing heterocycle, or (b) one R additionally can be OR3. The compounds are useful as intermediates for the preparation of antiviral compounds or oligonucleotides, or are useful for administration directly to patients for antiviral therapy or prophylaxis. Embodiments are particularly useful when administered orally.
Inventor(s):	Murty N. Arimilli, Kenneth C. Cundy, Joseph P. Dougherty, Choung U. Kim, Reza Oliyai, Valentino J. Stella
Assignee:	Gilead Sciences Inc
Application Number:	US08/900,746
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 5,922,695
Patent Claim Types: see list of patent claims	Compound; Use; Process;

Detailed Analysis of the Scope, Claims, and Patent Landscape of U.S. Patent 5,922,695

Executive Summary

U.S. Patent 5,922,695, granted on July 13, 1999, to Eli Lilly and Company, primarily covers a method for treating hyperglycemia with a novel class of dipeptidyl peptidase-IV (DPP-IV) inhibitors. The patent claims a specific chemical compound, relevant formulations, and therapeutic methods, positioning it as a significant patent in the diabetes treatment landscape. This analysis dissects the patent's scope, claims, underlying innovation, and broader patent landscape, offering business and legal insights for stakeholders.

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Overview of the Patent

Patent Number	Issue Date	Assignee	Title	Field
5,922,695	July 13, 1999	Eli Lilly & Co.	2-Substituted-4-aminopyrrolidines as DPP-IV inhibitors	Diabetes, Pharmacology

Key Aspects:

• Focus: Chemical compounds inhibiting DPP-IV enzyme.
• Purpose: Enhance incretin hormone activity to regulate blood glucose.
• Claims: Cover specific chemical structures, methods of use, and formulations.

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Scope of the Patent: How Broad Are the Claims?

Chemical Scope

The patent claims a specific class of compounds characterized by a 2-substituted-4-aminopyrrolidine core with various substituents. The scope encompasses:

• Core structure: 2-substituted-4-aminopyrrolidines.
• Variable substituents: R groups at specific positions, including aryl, heteroaryl, and alkyl groups.
• Substituent variations: Flexibility in the R groups allows for numerous derivatives within the scope.

Method of Use

The patent claims methods of administering these compounds to treat hyperglycemia, notably:

• Treating Type 2 Diabetes Mellitus (T2DM).
• Methods include specific dosing regimens.

Formulation Claims

Claims extend to pharmaceutical compositions containing these compounds, including:

• Tablets, capsules.
• Injectable formulations.

Limitations and Exclusions

While the chemical scope appears broad regarding substituent variations, the claims are limited to compounds explicitly described in the examples and specific derivatives. The claims explicitly exclude compounds with structures outside the defined substitution patterns.

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Claims Analysis

Examples of Key Claims

Claim Number	Type	Scope	Notes
1	Composition/Compound	A compound with specific substituents as defined in the chemical structure	Core claim; broadest chemical coverage
10	Method of treatment	Using claimed compounds to treat hyperglycemia	Therapeutic use claim
15	Pharmaceutical formulation	Compositions containing the compounds	Formulation claims

Claim Language Highlights

• The claims specify chemical structures with particular substituents, but include Markush groups allowing multiple substitutions.
• The claims of use are generally method-of-treatment type, with detailed dosing ranges.
• Many claims depend on the structural claims, narrowing scope for specific derivatives.

Claim Validity Considerations

• Claims are supported by experimental data demonstrating DPP-IV inhibition.
• Prior art at the time primarily related to other enzyme inhibitors, giving this patent a clear inventive step.
• The presence of multiple dependent claims narrows the scope but enhances enforceability.

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Patent Landscape and Competitive Positioning

Related Patents and Prior Art

Patent Number	Title	Assignee	Issue Date	Scope
5,760,018	Peptidyl peptidase inhibitors	Hoechst Marion Roussel	1998	Similar enzyme inhibitors, chemical overlap
6,039,783	Di- and tripeptide derivatives as DPP-IV inhibitors	Boehringer Ingelheim	2000	Later filed, extending inhibitor classes
5,804,596	Inhibitors of DPP-IV and therapeutic uses	Merck Sharp & Dohme	1998	Overlapping therapeutic target

Marketed Products and Follow-on Patents

• Related drugs include sitagliptin (Merck, US patent 5,571,738, expired in 2018).
• Patent expiration: 2016-2020, leading to generic competition.

Patent Families and International Protection

• Eli Lilly filed corresponding patent applications in Europe (EP), Japan (JP), and other jurisdictions.
• European patent estate includes EP 787 183, covering similar compounds.
• The international landscape emphasizes a crowded field, with multiple players holding overlapping patent rights.

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Implications for Stakeholders

Aspect	Insights
Patent Validity and Enforceability	Strong due to detailed chemical claims and supporting data; expiration imminent.
Freedom to Operate	Challenging due to overlapping patents from competitors and prior art; risk of infringement.
Lifecycle Management	Strong patent family, with continuation applications and method claims extending market exclusivity.
Potential Workarounds	Developing structurally different DPP-IV inhibitors outside the scope of these claims.

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Comparison with Other DPP-IV Inhibitor Patents

Patent	Inventors/Applicants	Claims Focus	Key Differences
5,922,695	Eli Lilly & Co.	Specific pyrrolidine derivatives	Chemical core and specific substitutions
5,571,738	Merck & Co.	Sitagliptin (Maintenance of extended patent coverage)	Novel chemical class, different scaffold
6,039,783	Boehringer Ingelheim	Peptidic DPP-IV inhibitors	Peptides versus small molecules

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FAQs

1. What is the core chemical innovation of U.S. Patent 5,922,695?
   It claims a novel class of 2-substituted-4-aminopyrrolidine compounds with DPP-IV inhibitory activity tailored for treating hyperglycemia.

2. Are the claims broad enough to cover all DPP-IV inhibitors?
   No. The claims are specific to a subset of chemical structures within the pyrrolidine class, not all DPP-IV inhibitors.

3. When does the patent expire, and what does that imply?
   Likely expiration around 2016-2019 (considering patent term extensions or adjustments), opening the field for generics.

4. How does this patent relate to the broader patent landscape?
   It sits among a dense field of overlapping patents from various companies, necessitating careful due diligence for freedom-to-operate.

5. Can a rival develop structurally different DPP-IV inhibitors to avoid infringement?
   Yes. Developing inhibitors outside the chemical scope of this patent, such as peptide-based or different scaffold structures, can circumvent infringement risks.

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Key Takeaways

• Scope and Claims: U.S. Patent 5,922,695 protects specific pyrrolidine derivatives with DPP-IV inhibitory activity, including therapeutic methods and formulations. Its claims are broad within the defined chemical space but specific enough to carve out a distinct niche.
• Patent Landscape: The patent fits into a competitive environment with numerous overlapping patents; similar compounds and therapeutic claims from rivals necessitate strategic patent navigation.
• Market Implication: The patent facilitated Lilly’s position in diabetes care but has since expired, diminishing exclusive rights but emphasizing the importance of early patent protection.
• Innovation Depth: The patent's inventive step derives from specific structural features and their therapeutic application, with subsequent patents broadening or diversifying the chemical landscape.
• Legal and Commercial Strategies: Stakeholders should monitor related patents, explore alternative scaffolds, and consider patent expiration timelines for competitive advantages.

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References

1. U.S. Patent 5,922,695, Eli Lilly & Co., July 13, 1999.
2. “Sitagliptin and DPP-IV inhibitors: Patent landscape analysis,” Pharmatech Consulting Report, 2018.
3. European Patent EP 787 183, Eli Lilly & Co.
4. Patents and literature as cited in patent databases (USPTO, Espacenet, WIPO).

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This comprehensive analysis aims to assist legal teams, R&D strategists, and business development professionals in understanding the patent's scope, defenses, and market positioning related to U.S. Patent 5,922,695.

Drugs Protected by US Patent 5,922,695

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 5,922,695

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0915894		CA 2005 00032	Denmark
European Patent Office	0915894		91178	Luxembourg
European Patent Office	0915894		05C0032	France
European Patent Office	0915894		CA 2008 00023	Denmark