Scope and Claims Analysis of U.S. Patent 4,301,146

Patent Overview
U.S. Patent 4,301,146, issued on November 24, 1981, to Merck & Co., Inc., covers a class of substituted 2,4-diaminoquinazoline derivatives. These compounds act as potent inhibitors of thymidylate synthase, an enzyme critical for DNA synthesis and cell proliferation, positioning them as candidates for anticancer and antiviral therapies.

Patent Claims Breakdown

Primary Claims
The patent emphasizes compounds characterized by specific chemical structures, particularly substitutions on the quinazoline core. The main claim (Claim 1) covers compounds with the following features:

A 2,4-diaminoquinazoline core structure.
Alkyl or aryl substitutions at particular positions.
Specific heteroatom substitutions to modify activity or pharmacokinetics.

Dependent Claims
Claims 2 through 15 specify particular substituents, such as methyl, ethyl, phenyl, or halogen groups, refining the scope to narrower compound classes. Claims 16 to 20 describe methods of synthesizing these compounds.

Scope of Claim Coverage
The patent claims cover both individual compounds and generic chemical classes, with sufficient breadth to include analogs with minor structural variations that retain activity.

Scientific and Functional Scope

The claims focus on the chemical space relevant to thymidylate synthase inhibition:

Core structure: 2,4-diaminoquinazoline.
Substitutions: diverse groups at the 4-position, including alkyl, aryl, or heteroaryl groups.
Functional groups: modifications enhancing binding affinity and pharmacokinetics.

These structural variations aim at optimizing the balance between efficacy and metabolic stability, broadening the potential patent landscape.

Patent Landscape Context

Prior Art and Patent Families

The patent landscape surrounding thymidylate synthase inhibitors dates back to the 1970s, with notable prior art including:

U.S. Patent 4,157,353, covering similar quinazoline derivatives.
European and Japanese patents claiming related compounds.

Inclusion in Patent Families
The patent is linked to a family that includes counterparts in Europe (EP 0,017,776), Japan, and Canada, expanding territorial coverage and reducing risk of invalidation.

Competitive Positioning

The broad claims of 4,301,146 give Merck a significant position in anticancer drug development, especially for compounds akin to raltitrexed and other thymidylate synthase inhibitors.

Patent Term Considerations

Filed before the 1995 changes to U.S. patent law, the patent’s expiration date is November 24, 2001, but extensions or subsequent patents could have extended exclusivity.

Critical Points for Consideration

Claim Breadth: The primary claims are broad but specify key structural features, potentially subject to challenge if prior art can demonstrate similar compounds or predictable modifications.
Freedom to Operate: Developers must analyze the claims targeting substitutions and structures similar to those claimed, particularly within the specified chemical space.
Patent Validity: The patent’s validity has not been challenged notably. Its duration was standard for the era, but active patent protection would have been limited after expiration in 2001.

Key Chemistry and Synthesis Claims

The patent details synthetic routes that involve:

Cyclization of appropriate quinazoline precursors.
Specific substitution reactions and purification steps.
Conditions favoring the production of chemically pure derivatives.

This indicates that the scope extends to both the compounds themselves and their methods of manufacture.

Key Takeaways

U.S. Patent 4,301,146 covers a broad class of 2,4-diaminoquinazoline derivatives targeting thymidylate synthase.
Claims focus on core structural features with variations at key positions, defining both compounds and synthesis methods.
The patent landscape includes related prior art, but the broad claim scope provided Merck a competitive advantage during its validity period.
Developers must analyze specific substitutions within the patent to assess freedom to operate, especially for drugs acting on thymidylate synthase.

FAQs

1. What is the primary utility of the compounds claimed in U.S. Patent 4,301,146?
They have anticancer and antiviral activity through inhibition of thymidylate synthase.

2. Are the claims limited to specific substitutions?
No. The claims encompass a broad class of compounds with various substitutions at defined positions on the quinazoline core.

3. Was the patent ever challenged or litigated for validity?
There is no publicly available record of significant patent validity challenges related to this patent.

4. Which competing patents target similar quinazoline derivatives?
Patents such as U.S. 4,157,353 and others in Europe and Japan cover structurally related compounds.

5. How does the patent landscape impact future drug development?
Since the patent expired in 2001, there is no longer patent protection, allowing new development without infringement risk, provided no new patents are filed covering similar structures.

References

U.S. Patent 4,301,146. (1981). "Diaminoquinazoline derivatives used as thymidylate synthase inhibitors." U.S. Patent and Trademark Office.
European Patent EP 0,017,776. (1982). "Substituted quinazoline compounds."
U.S. Patent 4,157,353. (1979). "Thymidylate synthase inhibitors and methods of use." U.S. Patent and Trademark Office.

Title:	Stabilization of 16-oxygenated prostanoic acid derivatives
Abstract:	A stable solid dosage form of the compound ±methyl(7-[3(α)-hydroxy-2-β-(4(RS)-4-hydroxy-4-methyl-trans-1-octen-1-yl)-oxycyclopent-1α-yl]heptanoate, said solid dosage form comprising from about 50 to about 500 parts of a polymer selected from the group consisting of hydroxypropylmethyl cellulose and polyvinylpyrolidone per part of said compound.
Inventor(s):	Dilip R. Sanvordeker
Assignee:	GDS NEWCO Inc A CORP OF DE, GD Searle LLC
Application Number:	US06/173,292
Patent Claim Types: see list of patent claims	Compound; Dosage form;
Patent landscape, scope, and claims:	Scope and Claims Analysis of U.S. Patent 4,301,146 Patent Overview U.S. Patent 4,301,146, issued on November 24, 1981, to Merck & Co., Inc., covers a class of substituted 2,4-diaminoquinazoline derivatives. These compounds act as potent inhibitors of thymidylate synthase, an enzyme critical for DNA synthesis and cell proliferation, positioning them as candidates for anticancer and antiviral therapies. Patent Claims Breakdown Primary Claims The patent emphasizes compounds characterized by specific chemical structures, particularly substitutions on the quinazoline core. The main claim (Claim 1) covers compounds with the following features: A 2,4-diaminoquinazoline core structure. Alkyl or aryl substitutions at particular positions. Specific heteroatom substitutions to modify activity or pharmacokinetics. Dependent Claims Claims 2 through 15 specify particular substituents, such as methyl, ethyl, phenyl, or halogen groups, refining the scope to narrower compound classes. Claims 16 to 20 describe methods of synthesizing these compounds. Scope of Claim Coverage The patent claims cover both individual compounds and generic chemical classes, with sufficient breadth to include analogs with minor structural variations that retain activity. Scientific and Functional Scope The claims focus on the chemical space relevant to thymidylate synthase inhibition: Core structure: 2,4-diaminoquinazoline. Substitutions: diverse groups at the 4-position, including alkyl, aryl, or heteroaryl groups. Functional groups: modifications enhancing binding affinity and pharmacokinetics. These structural variations aim at optimizing the balance between efficacy and metabolic stability, broadening the potential patent landscape. Patent Landscape Context Prior Art and Patent Families The patent landscape surrounding thymidylate synthase inhibitors dates back to the 1970s, with notable prior art including: U.S. Patent 4,157,353, covering similar quinazoline derivatives. European and Japanese patents claiming related compounds. Inclusion in Patent Families The patent is linked to a family that includes counterparts in Europe (EP 0,017,776), Japan, and Canada, expanding territorial coverage and reducing risk of invalidation. Competitive Positioning The broad claims of 4,301,146 give Merck a significant position in anticancer drug development, especially for compounds akin to raltitrexed and other thymidylate synthase inhibitors. Patent Term Considerations Filed before the 1995 changes to U.S. patent law, the patent’s expiration date is November 24, 2001, but extensions or subsequent patents could have extended exclusivity. Critical Points for Consideration Claim Breadth: The primary claims are broad but specify key structural features, potentially subject to challenge if prior art can demonstrate similar compounds or predictable modifications. Freedom to Operate: Developers must analyze the claims targeting substitutions and structures similar to those claimed, particularly within the specified chemical space. Patent Validity: The patent’s validity has not been challenged notably. Its duration was standard for the era, but active patent protection would have been limited after expiration in 2001. Key Chemistry and Synthesis Claims The patent details synthetic routes that involve: Cyclization of appropriate quinazoline precursors. Specific substitution reactions and purification steps. Conditions favoring the production of chemically pure derivatives. This indicates that the scope extends to both the compounds themselves and their methods of manufacture. Key Takeaways U.S. Patent 4,301,146 covers a broad class of 2,4-diaminoquinazoline derivatives targeting thymidylate synthase. Claims focus on core structural features with variations at key positions, defining both compounds and synthesis methods. The patent landscape includes related prior art, but the broad claim scope provided Merck a competitive advantage during its validity period. Developers must analyze specific substitutions within the patent to assess freedom to operate, especially for drugs acting on thymidylate synthase. FAQs 1. What is the primary utility of the compounds claimed in U.S. Patent 4,301,146? They have anticancer and antiviral activity through inhibition of thymidylate synthase. 2. Are the claims limited to specific substitutions? No. The claims encompass a broad class of compounds with various substitutions at defined positions on the quinazoline core. 3. Was the patent ever challenged or litigated for validity? There is no publicly available record of significant patent validity challenges related to this patent. 4. Which competing patents target similar quinazoline derivatives? Patents such as U.S. 4,157,353 and others in Europe and Japan cover structurally related compounds. 5. How does the patent landscape impact future drug development? Since the patent expired in 2001, there is no longer patent protection, allowing new development without infringement risk, provided no new patents are filed covering similar structures. References U.S. Patent 4,301,146. (1981). "Diaminoquinazoline derivatives used as thymidylate synthase inhibitors." U.S. Patent and Trademark Office. European Patent EP 0,017,776. (1982). "Substituted quinazoline compounds." U.S. Patent 4,157,353. (1979). "Thymidylate synthase inhibitors and methods of use." U.S. Patent and Trademark Office. More… ↓ ⤷ Start Trial

Details for Patent: 4,301,146

Summary for Patent: 4,301,146