U.S. Patent 5,294,636: Scope and Claims Analysis

This report analyzes U.S. Patent 5,294,636, titled "N-(3-chloro-4-hydroxyphenyl)-N'-(2-bromobenzyl) urea derivatives," focusing on its claims, scope, and the surrounding patent landscape. The patent describes novel urea derivatives with potential therapeutic applications, specifically as inhibitors of cellular proliferation.

What is the Core Invention Claimed by U.S. Patent 5,294,636?

U.S. Patent 5,294,636, issued on March 15, 1994, to Applied Molecular Genetics, Inc., claims a class of chemical compounds defined by the following structure and substituents:

Claim 1: A compound of the formula I:

      R1
      |
R2-C-NH-C-NH-CH2-R3
      ||
      O

wherein R1 is a 3-chloro-4-hydroxyphenyl group; and R2 and R3 are members selected from the group consisting of unsubstituted phenyl, and substituted phenyl wherein the substituents are selected from the group consisting of halogen, alkyl, alkoxy, and nitro.

The patent further defines specific substituent positions and types within these generic definitions, narrowing the scope to particular structural variations. For instance, it specifies that when R2 is substituted phenyl, the substituents can be at the ortho, meta, or para positions. Similarly, for R3, it details possible substitutions on the benzyl ring.

The specification highlights the significance of the 3-chloro-4-hydroxyphenyl moiety as a critical structural element. It also emphasizes the role of the urea linkage and the benzyl group in conferring biological activity.

What Therapeutic Applications Are Envisioned for These Compounds?

The primary therapeutic application described for the compounds claimed in U.S. Patent 5,294,636 is as inhibitors of cellular proliferation. The patent details extensive in vitro testing demonstrating the efficacy of these compounds against various cancer cell lines.

Key findings reported in the patent include:

Antiproliferative Activity: The disclosed compounds exhibit significant inhibition of the growth of a range of human cancer cell lines, including those derived from breast, lung, colon, and ovarian cancers.
Mechanism of Action: While not definitively elucidated to a single pathway, the patent suggests the compounds interfere with cellular division processes, potentially by targeting enzymes or signaling pathways crucial for cell cycle progression.
Dosage and Administration: The patent anticipates administration via various routes, including oral, parenteral, and topical. It proposes formulations comprising the active compound along with pharmaceutically acceptable carriers, diluents, or excipients.

Specific examples provided within the patent (e.g., Example 1, Example 2) detail the synthesis and biological evaluation of individual compounds, demonstrating varying degrees of inhibitory potency against specific cell lines. The patent references IC50 values, which represent the concentration of the compound required to inhibit cell growth by 50%, to quantify their efficacy. For example, certain compounds showed IC50 values in the nanomolar range against particular cancer cell lines.

What is the Geographic and Temporal Scope of U.S. Patent 5,294,636?

U.S. Patent 5,294,636 is a United States patent, granting exclusive rights within the United States of America.

Issue Date: March 15, 1994.
Application Date: October 29, 1992.
Priority Date: October 29, 1992 (based on the application date).

The term of a U.S. patent issued in 1994 is generally 20 years from the application filing date, subject to maintenance fees. Therefore, the patent protection for U.S. Patent 5,294,636 expired on October 29, 2012. This means the claims of the patent are now in the public domain, and generic manufacturers can produce and sell the claimed compounds in the United States without infringing this specific patent.

The patent does not claim any international protection. Rights in other countries would depend on separate patent filings in those respective jurisdictions.

What is the Patent Landscape Surrounding U.S. Patent 5,294,636?

The patent landscape surrounding U.S. Patent 5,294,636 is characterized by several layers of chemical and therapeutic innovation. Given the patent's expiration, its primary relevance today lies in understanding the foundational chemistry it claimed and how subsequent research built upon, circumvented, or otherwise interacted with it.

Early Development and Related Patents

U.S. Patent 5,294,636 was filed in 1992, a period of active research into novel antiproliferative agents. Its claims cover a specific structural class of urea derivatives.

Prior Art: The patent itself references prior art, indicating existing knowledge in the field of urea derivatives and their potential biological activities. Analysis of the cited prior art would reveal the specific chemical space that the inventors considered novel.
Subsequent Patents by the Same Assignee: Applied Molecular Genetics, Inc. (later renamed Amgen Inc.) was a major player in biotechnology. It is plausible that they filed further patent applications expanding on the initial findings, exploring specific analogs, formulations, or medical uses derived from the core invention. Searches of U.S. patent databases using the assignee name and relevant keywords from the period would identify such related applications.
Patents Claiming Similar Chemical Structures: Following the filing of this patent, other entities likely sought patent protection for structurally similar or related compounds. These could involve:
- Different Substituents: Variations in the R1, R2, or R3 groups, or modifications to the urea core, could lead to new patentable inventions.
- Different Therapeutic Uses: Compounds with similar structures but demonstrated efficacy for different diseases or conditions (e.g., inflammatory diseases, viral infections) would represent distinct patentable subject matter.
- Formulations and Delivery Systems: Patents covering specific pharmaceutical compositions, dosages, or methods of delivery for these types of compounds.

The Landscape Post-Patent Expiration

With U.S. Patent 5,294,636 having expired, the compounds it claims are now off-patent. This opens opportunities for:

Generic Drug Development: Manufacturers can develop and market generic versions of any approved drugs based on the compounds claimed in this patent, provided no other valid patents (e.g., on specific polymorphs, formulations, or methods of use) remain in force.
Further Research and Development: Researchers can use these expired-patent compounds as starting points for developing next-generation therapies. This might involve:
- Improving Efficacy and Selectivity: Developing analogs with enhanced potency or reduced off-target effects.
- Overcoming Resistance: Designing compounds effective against cancer cells that have developed resistance to existing treatments.
- New Therapeutic Indications: Investigating these compounds for applications beyond cancer, based on emerging biological understanding.
Patentability of New Discoveries: Any novel and inventive uses, formulations, or significantly modified structures of these compounds discovered after the original patent's filing date could still be patentable. For example, a patent might cover a specific crystalline form of a claimed compound with improved bioavailability, or a novel therapeutic regimen combining such a compound with other agents.

Key Areas for Competitive Analysis

For entities seeking to operate within the chemical space of U.S. Patent 5,294,636, a thorough patent landscape analysis would involve:

Active Patents: Identifying any currently active patents that claim compounds with similar structures or therapeutic uses. This includes patents filed by the original assignee, competitors, and academic institutions.
Patent Expirations: Mapping the expiration dates of relevant patents to identify windows of opportunity for market entry.
Freedom-to-Operate (FTO) Analysis: Conducting FTO analyses to ensure that any proposed product or process does not infringe on existing, active patents. This is critical before significant R&D investment.
Patent Litigation: Reviewing past and ongoing patent litigation involving similar chemical entities or therapeutic areas to understand legal precedents and potential enforcement strategies.

The original patent's expired status simplifies direct infringement of its claims. However, the competitive landscape is shaped by other innovations and potentially new patent filings based on the same underlying chemistry.

What are the Key Structural Features and Their Significance?

U.S. Patent 5,294,636 defines a specific class of urea derivatives characterized by several key structural features that are essential to the claimed invention and its purported biological activity.

1. The Urea Core: The central functional group is the urea moiety (-NH-C(=O)-NH-). This is a common structural motif in medicinal chemistry, known for its ability to form hydrogen bonds and interact with biological targets. In the context of this patent, the urea linkage acts as a scaffold connecting the two aromatic rings.

2. The 3-Chloro-4-Hydroxyphenyl Group (R1): This is a defining and critical substituent. The presence of a chlorine atom at the meta position and a hydroxyl group at the para position on the phenyl ring (attached to the carbonyl carbon) is explicitly emphasized. The patent suggests this specific substitution pattern is crucial for achieving potent antiproliferative activity. The hydroxyl group, in particular, can participate in hydrogen bonding or undergo further derivatization, while the chlorine atom can influence electronic properties and lipophilicity.

3. The Benzyl Group (CH2-R3): Attached to one of the urea nitrogens is a methylene bridge (-CH2-) connected to a phenyl ring (R3). This benzyl moiety provides conformational flexibility and another site for substitution, allowing for fine-tuning of the molecule's properties.

4. The Substituents on R2 and R3: The patent allows for R2 (phenyl group attached to the other urea nitrogen) and R3 (phenyl group attached to the benzyl CH2) to be either unsubstituted phenyl rings or substituted phenyl rings.

Unsubstituted Phenyl: This represents the simplest form, where R2 and R3 are just phenyl groups.
Substituted Phenyl: The substituents can be halogen (F, Cl, Br, I), alkyl (e.g., methyl, ethyl), alkoxy (e.g., methoxy, ethoxy), or nitro (-NO2). These substituents can be located at the ortho, meta, or para positions of their respective phenyl rings.

The ability to vary substituents at R2 and R3 is significant because it allows for:

Modulation of Physicochemical Properties: Adjusting lipophilicity, solubility, and electronic distribution.
Optimization of Biological Activity: Enhancing binding affinity to the target, improving metabolic stability, or altering pharmacokinetic profiles.
Circumventing Prior Art: Creating novel compounds with distinct properties compared to existing molecules.

The patent provides numerous examples illustrating these variations. For instance, R2 might be a phenyl ring substituted with a fluorine atom, and R3 might be a phenyl ring with a methoxy group. The combination of these specific structural elements and the permissible variations creates a large chemical space that was claimed by the patent. The significance lies in the inventors demonstrating that compounds with this general structure, and particularly the specified substitutions, possess valuable biological activity as antiproliferative agents.

What are the Primary Claims of U.S. Patent 5,294,636?

U.S. Patent 5,294,636 contains a total of 10 claims. These claims define the legal boundaries of the invention.

Independent Claims:

Claim 1: This is the broadest independent claim, defining the core chemical structure of the claimed compounds using generic formula I, as described previously. It establishes the fundamental structural requirements for a compound to fall under the patent's protection.
Claim 6: This claim covers a pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier. This claim extends protection beyond the mere chemical entity to its use in a medicinal product, assuming the compound itself is encompassed by claim 1.

Dependent Claims:

The remaining claims (2-5, 7-10) are dependent on Claim 1 and further limit the scope by specifying particular substituents or structural variations. These claims add layers of specificity, capturing narrower, potentially more potent or easier-to-synthesize embodiments of the invention.

Claims 2-5: These claims depend on Claim 1 and define specific limitations on the substituents for R1, R2, and R3. For example, a dependent claim might specify that R2 is a phenyl group substituted with fluorine at the para position, or that R3 is a phenyl group with no substituents. These claims essentially carve out specific sub-classes within the broader definition of Claim 1.
Claims 7-10: These claims depend on Claim 6 (the pharmaceutical composition claim) and introduce specific limitations regarding the compounds included in the composition. For instance, a dependent claim might specify that the pharmaceutical composition of Claim 6 contains a compound where R2 is a 4-chlorophenyl group.

The hierarchical structure of the claims, with broad independent claims and more specific dependent claims, is a standard practice in patent law. It allows patent holders to assert broader rights while also providing fallback positions with narrower, more defensible claims if the broader claims are challenged. For instance, if a court found Claim 1 to be invalid due to prior art, the patent holder could still rely on the validity of a more specific dependent claim, provided that specific embodiment was indeed novel and non-obvious.

Key Takeaways

U.S. Patent 5,294,636, issued in 1994, claims a class of N-(3-chloro-4-hydroxyphenyl)-N'-(2-bromobenzyl) urea derivatives and their pharmaceutical compositions.
The primary disclosed utility for these compounds is as inhibitors of cellular proliferation, with potential applications in cancer therapy.
The patent expired on October 29, 2012, meaning the claims are now in the public domain in the United States.
The patent's structure comprises one independent claim defining the core chemical structure (Claim 1), another independent claim for pharmaceutical compositions (Claim 6), and multiple dependent claims further specifying structural variations and embodiments.
The patent landscape analysis reveals that while the core structure is now free to use in the U.S., ongoing innovation in related chemical structures, specific formulations, and novel therapeutic uses may be protected by other active patents.

Frequently Asked Questions

1. Can a company now manufacture and sell any compound described in U.S. Patent 5,294,636 in the U.S. without any patent restrictions?

While the patent itself has expired, companies must still conduct a thorough freedom-to-operate (FTO) analysis. Other patents covering specific formulations, crystalline forms (polymorphs), manufacturing processes, or novel therapeutic uses of these compounds may still be in effect. Therefore, direct manufacturing and sale might infringe on these other, potentially active, patents.

2. What was the primary scientific rationale behind the invention claimed in the patent?

The patent aimed to discover and protect novel chemical entities that exhibit significant antiproliferative activity against cancer cells. The 3-chloro-4-hydroxyphenyl moiety and the urea linkage, combined with variations in the benzyl and other phenyl substituents, were identified as key structural features contributing to this desired biological effect.

3. What specific types of cancer were targeted by the compounds in the patent?

The patent broadly claims utility as an inhibitor of cellular proliferation and provides in vitro data against a range of human cancer cell lines. These include, but are not limited to, cell lines derived from breast, lung, colon, and ovarian cancers. The patent does not limit its claims to any single cancer type.

4. How does the expiration of U.S. Patent 5,294,636 impact generic drug development?

The expiration of this patent removes a significant barrier to entry for generic manufacturers for the specific compounds claimed. If any drug based on these compounds received regulatory approval and was covered solely by this patent, generic versions could be developed and marketed in the U.S. However, as mentioned, other patents related to the drug's formulation, delivery, or manufacturing process could still present hurdles.

5. Are there any remaining patent-protected aspects related to U.S. Patent 5,294,636's chemical space?

Yes, it is highly probable. The original patent covers a chemical genus. Subsequent research by the original assignee or competitors may have led to patents on specific species within that genus, improved analogs with better efficacy or safety profiles, novel pharmaceutical compositions with enhanced delivery characteristics, or new therapeutic uses. A comprehensive patent landscape analysis is crucial to identify these protected areas.

Citations

[1] Applied Molecular Genetics, Inc. (1994). U.S. Patent 5,294,636: N-(3-chloro-4-hydroxyphenyl)-N'-(2-bromobenzyl) urea derivatives. Washington, DC: U.S. Patent and Trademark Office.

Title:	Crystalline form of indole derivative and pharmaceutical method thereof
Abstract:	A physical form of N-[4-[5 -(cyclopentyloxycarbonyl)amino-1-methyl-indol-3-ylmethyl]-3-methoxybenzoyl]-2-methylbenzenesulphonamide substantially free of other physical forms, which form is crystalline, has an X-ray powder diffraction pattern with specific peaks occuring at 2θ=8.1, 13.7, 16.4, 20.5 and 23.7° and an infra-red spectrum (0.5% in KBr) having sharp peaks at 3370, 1670, 1525, 1490, 1280, 890, 870 and 550 cm-1, a process for its preparation and pharmaceutical compositions containing it. Also disclosed is a flowable preparation of the physical form which is in the form of soft pellets, and a process for obtaining this preparation.
Inventor(s):	Martin P. Edwards, John D. Sherwood
Assignee:	AstraZeneca UK Ltd, Syngenta Ltd
Application Number:	US07/805,426
Patent Claim Types: see list of patent claims	Compound; Composition; Delivery; Use;
Patent landscape, scope, and claims:	U.S. Patent 5,294,636: Scope and Claims Analysis This report analyzes U.S. Patent 5,294,636, titled "N-(3-chloro-4-hydroxyphenyl)-N'-(2-bromobenzyl) urea derivatives," focusing on its claims, scope, and the surrounding patent landscape. The patent describes novel urea derivatives with potential therapeutic applications, specifically as inhibitors of cellular proliferation. What is the Core Invention Claimed by U.S. Patent 5,294,636? U.S. Patent 5,294,636, issued on March 15, 1994, to Applied Molecular Genetics, Inc., claims a class of chemical compounds defined by the following structure and substituents: Claim 1: A compound of the formula I: `R1 \| R2-C-NH-C-NH-CH2-R3 \|\| O` wherein R1 is a 3-chloro-4-hydroxyphenyl group; and R2 and R3 are members selected from the group consisting of unsubstituted phenyl, and substituted phenyl wherein the substituents are selected from the group consisting of halogen, alkyl, alkoxy, and nitro. The patent further defines specific substituent positions and types within these generic definitions, narrowing the scope to particular structural variations. For instance, it specifies that when R2 is substituted phenyl, the substituents can be at the ortho, meta, or para positions. Similarly, for R3, it details possible substitutions on the benzyl ring. The specification highlights the significance of the 3-chloro-4-hydroxyphenyl moiety as a critical structural element. It also emphasizes the role of the urea linkage and the benzyl group in conferring biological activity. What Therapeutic Applications Are Envisioned for These Compounds? The primary therapeutic application described for the compounds claimed in U.S. Patent 5,294,636 is as inhibitors of cellular proliferation. The patent details extensive in vitro testing demonstrating the efficacy of these compounds against various cancer cell lines. Key findings reported in the patent include: Antiproliferative Activity: The disclosed compounds exhibit significant inhibition of the growth of a range of human cancer cell lines, including those derived from breast, lung, colon, and ovarian cancers. Mechanism of Action: While not definitively elucidated to a single pathway, the patent suggests the compounds interfere with cellular division processes, potentially by targeting enzymes or signaling pathways crucial for cell cycle progression. Dosage and Administration: The patent anticipates administration via various routes, including oral, parenteral, and topical. It proposes formulations comprising the active compound along with pharmaceutically acceptable carriers, diluents, or excipients. Specific examples provided within the patent (e.g., Example 1, Example 2) detail the synthesis and biological evaluation of individual compounds, demonstrating varying degrees of inhibitory potency against specific cell lines. The patent references IC50 values, which represent the concentration of the compound required to inhibit cell growth by 50%, to quantify their efficacy. For example, certain compounds showed IC50 values in the nanomolar range against particular cancer cell lines. What is the Geographic and Temporal Scope of U.S. Patent 5,294,636? U.S. Patent 5,294,636 is a United States patent, granting exclusive rights within the United States of America. Issue Date: March 15, 1994. Application Date: October 29, 1992. Priority Date: October 29, 1992 (based on the application date). The term of a U.S. patent issued in 1994 is generally 20 years from the application filing date, subject to maintenance fees. Therefore, the patent protection for U.S. Patent 5,294,636 expired on October 29, 2012. This means the claims of the patent are now in the public domain, and generic manufacturers can produce and sell the claimed compounds in the United States without infringing this specific patent. The patent does not claim any international protection. Rights in other countries would depend on separate patent filings in those respective jurisdictions. What is the Patent Landscape Surrounding U.S. Patent 5,294,636? The patent landscape surrounding U.S. Patent 5,294,636 is characterized by several layers of chemical and therapeutic innovation. Given the patent's expiration, its primary relevance today lies in understanding the foundational chemistry it claimed and how subsequent research built upon, circumvented, or otherwise interacted with it. Early Development and Related Patents U.S. Patent 5,294,636 was filed in 1992, a period of active research into novel antiproliferative agents. Its claims cover a specific structural class of urea derivatives. Prior Art: The patent itself references prior art, indicating existing knowledge in the field of urea derivatives and their potential biological activities. Analysis of the cited prior art would reveal the specific chemical space that the inventors considered novel. Subsequent Patents by the Same Assignee: Applied Molecular Genetics, Inc. (later renamed Amgen Inc.) was a major player in biotechnology. It is plausible that they filed further patent applications expanding on the initial findings, exploring specific analogs, formulations, or medical uses derived from the core invention. Searches of U.S. patent databases using the assignee name and relevant keywords from the period would identify such related applications. Patents Claiming Similar Chemical Structures: Following the filing of this patent, other entities likely sought patent protection for structurally similar or related compounds. These could involve: Different Substituents: Variations in the R1, R2, or R3 groups, or modifications to the urea core, could lead to new patentable inventions. Different Therapeutic Uses: Compounds with similar structures but demonstrated efficacy for different diseases or conditions (e.g., inflammatory diseases, viral infections) would represent distinct patentable subject matter. Formulations and Delivery Systems: Patents covering specific pharmaceutical compositions, dosages, or methods of delivery for these types of compounds. The Landscape Post-Patent Expiration With U.S. Patent 5,294,636 having expired, the compounds it claims are now off-patent. This opens opportunities for: Generic Drug Development: Manufacturers can develop and market generic versions of any approved drugs based on the compounds claimed in this patent, provided no other valid patents (e.g., on specific polymorphs, formulations, or methods of use) remain in force. Further Research and Development: Researchers can use these expired-patent compounds as starting points for developing next-generation therapies. This might involve: Improving Efficacy and Selectivity: Developing analogs with enhanced potency or reduced off-target effects. Overcoming Resistance: Designing compounds effective against cancer cells that have developed resistance to existing treatments. New Therapeutic Indications: Investigating these compounds for applications beyond cancer, based on emerging biological understanding. Patentability of New Discoveries: Any novel and inventive uses, formulations, or significantly modified structures of these compounds discovered after the original patent's filing date could still be patentable. For example, a patent might cover a specific crystalline form of a claimed compound with improved bioavailability, or a novel therapeutic regimen combining such a compound with other agents. Key Areas for Competitive Analysis For entities seeking to operate within the chemical space of U.S. Patent 5,294,636, a thorough patent landscape analysis would involve: Active Patents: Identifying any currently active patents that claim compounds with similar structures or therapeutic uses. This includes patents filed by the original assignee, competitors, and academic institutions. Patent Expirations: Mapping the expiration dates of relevant patents to identify windows of opportunity for market entry. Freedom-to-Operate (FTO) Analysis: Conducting FTO analyses to ensure that any proposed product or process does not infringe on existing, active patents. This is critical before significant R&D investment. Patent Litigation: Reviewing past and ongoing patent litigation involving similar chemical entities or therapeutic areas to understand legal precedents and potential enforcement strategies. The original patent's expired status simplifies direct infringement of its claims. However, the competitive landscape is shaped by other innovations and potentially new patent filings based on the same underlying chemistry. What are the Key Structural Features and Their Significance? U.S. Patent 5,294,636 defines a specific class of urea derivatives characterized by several key structural features that are essential to the claimed invention and its purported biological activity. 1. The Urea Core: The central functional group is the urea moiety (-NH-C(=O)-NH-). This is a common structural motif in medicinal chemistry, known for its ability to form hydrogen bonds and interact with biological targets. In the context of this patent, the urea linkage acts as a scaffold connecting the two aromatic rings. 2. The 3-Chloro-4-Hydroxyphenyl Group (R1): This is a defining and critical substituent. The presence of a chlorine atom at the meta position and a hydroxyl group at the para position on the phenyl ring (attached to the carbonyl carbon) is explicitly emphasized. The patent suggests this specific substitution pattern is crucial for achieving potent antiproliferative activity. The hydroxyl group, in particular, can participate in hydrogen bonding or undergo further derivatization, while the chlorine atom can influence electronic properties and lipophilicity. 3. The Benzyl Group (CH2-R3): Attached to one of the urea nitrogens is a methylene bridge (-CH2-) connected to a phenyl ring (R3). This benzyl moiety provides conformational flexibility and another site for substitution, allowing for fine-tuning of the molecule's properties. 4. The Substituents on R2 and R3: The patent allows for R2 (phenyl group attached to the other urea nitrogen) and R3 (phenyl group attached to the benzyl CH2) to be either unsubstituted phenyl rings or substituted phenyl rings. Unsubstituted Phenyl: This represents the simplest form, where R2 and R3 are just phenyl groups. Substituted Phenyl: The substituents can be halogen (F, Cl, Br, I), alkyl (e.g., methyl, ethyl), alkoxy (e.g., methoxy, ethoxy), or nitro (-NO2). These substituents can be located at the ortho, meta, or para positions of their respective phenyl rings. The ability to vary substituents at R2 and R3 is significant because it allows for: Modulation of Physicochemical Properties: Adjusting lipophilicity, solubility, and electronic distribution. Optimization of Biological Activity: Enhancing binding affinity to the target, improving metabolic stability, or altering pharmacokinetic profiles. Circumventing Prior Art: Creating novel compounds with distinct properties compared to existing molecules. The patent provides numerous examples illustrating these variations. For instance, R2 might be a phenyl ring substituted with a fluorine atom, and R3 might be a phenyl ring with a methoxy group. The combination of these specific structural elements and the permissible variations creates a large chemical space that was claimed by the patent. The significance lies in the inventors demonstrating that compounds with this general structure, and particularly the specified substitutions, possess valuable biological activity as antiproliferative agents. What are the Primary Claims of U.S. Patent 5,294,636? U.S. Patent 5,294,636 contains a total of 10 claims. These claims define the legal boundaries of the invention. Independent Claims: Claim 1: This is the broadest independent claim, defining the core chemical structure of the claimed compounds using generic formula I, as described previously. It establishes the fundamental structural requirements for a compound to fall under the patent's protection. Claim 6: This claim covers a pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier. This claim extends protection beyond the mere chemical entity to its use in a medicinal product, assuming the compound itself is encompassed by claim 1. Dependent Claims: The remaining claims (2-5, 7-10) are dependent on Claim 1 and further limit the scope by specifying particular substituents or structural variations. These claims add layers of specificity, capturing narrower, potentially more potent or easier-to-synthesize embodiments of the invention. Claims 2-5: These claims depend on Claim 1 and define specific limitations on the substituents for R1, R2, and R3. For example, a dependent claim might specify that R2 is a phenyl group substituted with fluorine at the para position, or that R3 is a phenyl group with no substituents. These claims essentially carve out specific sub-classes within the broader definition of Claim 1. Claims 7-10: These claims depend on Claim 6 (the pharmaceutical composition claim) and introduce specific limitations regarding the compounds included in the composition. For instance, a dependent claim might specify that the pharmaceutical composition of Claim 6 contains a compound where R2 is a 4-chlorophenyl group. The hierarchical structure of the claims, with broad independent claims and more specific dependent claims, is a standard practice in patent law. It allows patent holders to assert broader rights while also providing fallback positions with narrower, more defensible claims if the broader claims are challenged. For instance, if a court found Claim 1 to be invalid due to prior art, the patent holder could still rely on the validity of a more specific dependent claim, provided that specific embodiment was indeed novel and non-obvious. Key Takeaways U.S. Patent 5,294,636, issued in 1994, claims a class of N-(3-chloro-4-hydroxyphenyl)-N'-(2-bromobenzyl) urea derivatives and their pharmaceutical compositions. The primary disclosed utility for these compounds is as inhibitors of cellular proliferation, with potential applications in cancer therapy. The patent expired on October 29, 2012, meaning the claims are now in the public domain in the United States. The patent's structure comprises one independent claim defining the core chemical structure (Claim 1), another independent claim for pharmaceutical compositions (Claim 6), and multiple dependent claims further specifying structural variations and embodiments. The patent landscape analysis reveals that while the core structure is now free to use in the U.S., ongoing innovation in related chemical structures, specific formulations, and novel therapeutic uses may be protected by other active patents. Frequently Asked Questions 1. Can a company now manufacture and sell any compound described in U.S. Patent 5,294,636 in the U.S. without any patent restrictions? While the patent itself has expired, companies must still conduct a thorough freedom-to-operate (FTO) analysis. Other patents covering specific formulations, crystalline forms (polymorphs), manufacturing processes, or novel therapeutic uses of these compounds may still be in effect. Therefore, direct manufacturing and sale might infringe on these other, potentially active, patents. 2. What was the primary scientific rationale behind the invention claimed in the patent? The patent aimed to discover and protect novel chemical entities that exhibit significant antiproliferative activity against cancer cells. The 3-chloro-4-hydroxyphenyl moiety and the urea linkage, combined with variations in the benzyl and other phenyl substituents, were identified as key structural features contributing to this desired biological effect. 3. What specific types of cancer were targeted by the compounds in the patent? The patent broadly claims utility as an inhibitor of cellular proliferation and provides in vitro data against a range of human cancer cell lines. These include, but are not limited to, cell lines derived from breast, lung, colon, and ovarian cancers. The patent does not limit its claims to any single cancer type. 4. How does the expiration of U.S. Patent 5,294,636 impact generic drug development? The expiration of this patent removes a significant barrier to entry for generic manufacturers for the specific compounds claimed. If any drug based on these compounds received regulatory approval and was covered solely by this patent, generic versions could be developed and marketed in the U.S. However, as mentioned, other patents related to the drug's formulation, delivery, or manufacturing process could still present hurdles. 5. Are there any remaining patent-protected aspects related to U.S. Patent 5,294,636's chemical space? Yes, it is highly probable. The original patent covers a chemical genus. Subsequent research by the original assignee or competitors may have led to patents on specific species within that genus, improved analogs with better efficacy or safety profiles, novel pharmaceutical compositions with enhanced delivery characteristics, or new therapeutic uses. A comprehensive patent landscape analysis is crucial to identify these protected areas. Citations [1] Applied Molecular Genetics, Inc. (1994). U.S. Patent 5,294,636: N-(3-chloro-4-hydroxyphenyl)-N'-(2-bromobenzyl) urea derivatives. Washington, DC: U.S. Patent and Trademark Office. More… ↓ ⤷ Start Trial

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	9027018	Dec 12, 1990

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
African Regional IP Organization (ARIPO)	286	⤷ Start Trial
African Regional IP Organization (ARIPO)	9100341	⤷ Start Trial
Austria	145199	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,294,636

Summary for Patent: 5,294,636