United States Drug Patent 7,220,742: Scope, Claims, and Landscape Analysis

What is the Core Technology Protected by US Patent 7,220,742?

US Patent 7,220,742, titled "Cyclic peptide analog of luteinizing hormone-releasing hormone" and issued on May 22, 2007, protects a class of cyclic peptide analogs of luteinizing hormone-releasing hormone (LHRH). These analogs are designed to act as agonists or antagonists of the LHRH receptor, thereby modulating gonadotropin release. The patent's primary focus is on specific substituted cyclic peptides with a defined amino acid sequence and chemical structure. The invention addresses limitations of prior LHRH analogs, aiming for improved pharmacokinetic properties, receptor binding affinity, and therapeutic efficacy [1].

The patent covers compounds characterized by a specific cyclic peptide structure, which includes a D-amino acid at position 6 and a non-natural amino acid at position 10. These structural modifications are crucial for conferring antagonist or agonist activity and stability against enzymatic degradation. The claims define the chemical structure of these compounds, including specific substitutions and the inclusion of certain D-amino acids and modified C-termini [1].

What are the Key Claims within US Patent 7,220,742?

The claims of US Patent 7,220,742 delineate the intellectual property rights granted. These claims are hierarchical, with independent claims defining the broadest scope and dependent claims providing narrower specifications.

Independent Claim 1: This claim defines a cyclic peptide having a specific sequence where the amino acid at position 6 is a D-amino acid and the amino acid at position 10 is a non-natural amino acid. The structure is further specified by a general formula that encompasses various substitutions at different positions of the peptide backbone, including positions 2, 3, 4, and 10. The core of this claim is the cyclic nature and the strategic placement of D-amino acids and non-natural amino acids to achieve biological activity [1].

Dependent Claims: A series of dependent claims further refine the scope by specifying particular amino acid residues at various positions and detailing the nature of the substitutions. For example, dependent claims specify particular D-amino acids at position 6, such as D-Nal(2), D-Phe(4-Cl), D-Pal(3), and D-Tpa(3). Similarly, specific non-natural amino acids at position 10 are detailed, including various substituted phenylalanines and other amino acid derivatives. These dependent claims define specific embodiments of the invention, providing protection for a narrower, more defined set of compounds [1].

Salt Forms and Pharmaceutical Compositions: The patent also includes claims covering pharmaceutically acceptable salts of the claimed cyclic peptides and pharmaceutical compositions containing these peptides. This extends protection beyond the active pharmaceutical ingredient (API) to the formulated drug product, encompassing various excipients and delivery systems designed for therapeutic administration [1].

Methods of Use: While the primary focus is on the composition of matter, the patent implicitly covers methods of use by claiming compounds useful for modulating LHRH receptor activity. Therapeutic applications, such as treating hormone-dependent cancers, endometriosis, and precocious puberty, are within the purview of the protected technology [1].

What is the Therapeutic Indication Targeted by the Patented Compounds?

The cyclic peptide analogs protected by US Patent 7,220,742 are designed for therapeutic applications related to the modulation of the LHRH pathway. LHRH (also known as gonadotropin-releasing hormone, GnRH) plays a central role in the regulation of the reproductive system by controlling the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary gland.

Oncology: A primary therapeutic indication for LHRH analogs, including those covered by this patent, is the treatment of hormone-dependent cancers. These include prostate cancer, breast cancer, and ovarian cancer, where tumor growth is stimulated by sex hormones (androgens and estrogens). LHRH agonists can downregulate the production of these hormones by suppressing LH and FSH release, thereby inhibiting tumor growth. LHRH antagonists directly block the LHRH receptor, achieving a similar suppressive effect [2].

Gynecological Disorders: The patent's technology is also applicable to the treatment of various gynecological conditions. These include:

Endometriosis: A condition where uterine tissue grows outside the uterus, causing pain and infertility. LHRH analogs can reduce estrogen levels, thereby shrinking endometrial implants.
Uterine Fibroids: Benign tumors in the uterus that can cause heavy bleeding and pain. Hormone suppression can lead to fibroid shrinkage.
Precocious Puberty: The onset of puberty at an unusually early age. LHRH agonists can temporarily halt puberty by suppressing gonadotropin release [3].

Other Applications: Potential applications may also extend to assisted reproductive technologies and the management of other conditions influenced by gonadal steroid production. The ability to finely tune the agonistic or antagonistic activity of these cyclic peptides allows for a range of therapeutic outcomes [1, 2].

Who are the Key Patentees and Assignees Associated with US Patent 7,220,742?

The primary patentee for US Patent 7,220,742 is listed as Aventis Pharmaceuticals Inc. Aventis Pharmaceuticals was a major pharmaceutical company formed through mergers, notably between Hoechst Marion Roussel and Rhône-Poulenc Rorer in 1999. In 2004, Aventis was acquired by Sanofi-Synthélabo, forming Sanofi-Aventis, which was later rebranded as Sanofi. Therefore, the ultimate assignee and rights holder for this patent is Sanofi.

Sanofi is a global biopharmaceutical company with a significant presence in areas including oncology, immunology, and rare diseases. The development and patenting of LHRH analogs align with Sanofi's strategic focus on therapeutic areas driven by hormonal regulation.

A review of patent litigation databases and patent assignment records confirms Sanofi's ownership and enforcement of this patent. Companies developing generic versions of LHRH analog drugs often engage in patent litigation with Sanofi concerning the validity and infringement of patents such as US Patent 7,220,742 [4].

What is the Status of US Patent 7,220,742?

US Patent 7,220,742 was issued on May 22, 2007. Patents in the United States have a term of 20 years from the date on which the application for the patent was filed, subject to the payment of maintenance fees.

The application for US Patent 7,220,742 was filed on June 11, 2003. Therefore, the patent term calculation is based on this filing date.

Patent Term End Date: June 11, 2023.

As of today's date, US Patent 7,220,742 has expired. The expiration of this patent is a critical event for the pharmaceutical industry, as it typically marks the point at which generic manufacturers may enter the market with competing products, provided they can demonstrate bioequivalence and meet regulatory requirements.

The expiration of this patent does not necessarily extinguish all intellectual property protection related to LHRH analogs. Sanofi, or other entities, may hold other patents covering different compounds, formulations, manufacturing processes, or methods of use that are still in effect. However, the specific claims protecting the compounds defined in US Patent 7,220,742 are no longer enforceable [1].

What is the Competitive Landscape and Patent Exclusivity Outlook for These LHRH Analogs?

The competitive landscape for LHRH analogs is characterized by a history of robust patent protection, followed by market entry of generics upon patent expiration. US Patent 7,220,742, now expired, was a key piece of intellectual property for Sanofi concerning specific cyclic peptide LHRH analogs.

Key LHRH Analog Drugs: Drugs based on LHRH analogs have been a cornerstone in treating hormone-dependent conditions for decades. Examples include:

Goserelin (Zoladex): An LHRH agonist.
Leuprolide (Lupron): An LHRH agonist.
Triptorelin (Trelstar): An LHRH agonist.
Degarelix (Firmagon): An LHRH antagonist.

The specific compounds claimed in US Patent 7,220,742 are understood to be related to certain LHRH antagonists. Historically, patents like this have protected the development of novel LHRH antagonists that offer distinct advantages over earlier agonists, such as faster onset of action and less of an initial surge in hormone levels.

Post-Expiration Landscape: With the expiration of US Patent 7,220,742, the market for the specific compounds it claims is now open to generic competition. This typically leads to a significant decrease in drug prices due to increased market competition. Generic manufacturers often develop their own formulations or manufacturing processes, and they may also rely on Paragraph IV certifications to challenge existing patents.

Remaining Exclusivity: While US Patent 7,220,742 has expired, Sanofi may still hold other patents that provide exclusivity for related products. These could include patents covering:

Formulations: Different delivery systems (e.g., long-acting injectables, oral formulations) or specific excipients.
Manufacturing Processes: Novel or more efficient methods of synthesizing the peptides.
New Indications: Patents for the use of these analogs in previously undisclosed or newly discovered therapeutic areas.
Subsequent Generation Compounds: Patents for second-generation or improved LHRH analogs with different chemical structures or enhanced properties.

Companies looking to enter this market should conduct thorough freedom-to-operate (FTO) analyses to identify any active patents that could be infringed by their products. This includes examining the patent portfolios of Sanofi and other active players in the LHRH analog space. The patent landscape for LHRH analogs is complex and requires ongoing monitoring due to potential new patent filings and litigation [4, 5].

What is the Patent Landscape for LHRH Receptor Modulators Beyond US Patent 7,220,742?

The patent landscape for LHRH receptor modulators is extensive and dynamic, reflecting the significant therapeutic value of these compounds. US Patent 7,220,742 represents a specific segment within this broader field.

Early Patents: The foundational patents for LHRH analogs, particularly agonists, were filed in the 1970s and 1980s. These patents protected the initial discovery and therapeutic applications of peptide analogs that mimicked or antagonized LHRH.

Innovations in Antagonists: The development of LHRH antagonists marked a significant advancement. These compounds offer a different mechanism of action compared to agonists, providing immediate suppression of gonadotropins without the initial flare. Patents in this area focus on novel chemical structures that enhance receptor binding affinity, improve stability, and optimize pharmacokinetic profiles. US Patent 7,220,742 falls within this category of innovations [2, 5].

Second and Third-Generation Analogs: Research continues to yield second and third-generation LHRH analogs. These often involve modifications to improve:

Delivery: Development of long-acting depot formulations (e.g., microspheres) that allow for infrequent administration (monthly, quarterly, or even annually). Patents covering these formulation technologies are crucial.
Potency and Selectivity: Further refinements in peptide chemistry to achieve higher potency, better receptor selectivity, and reduced off-target effects.
Oral Bioavailability: While challenging for peptides, research into oral delivery of LHRH modulators is an ongoing area of patent interest.

New Indications and Combinations: Patents are also filed for novel uses of existing LHRH analogs. This includes their application in new disease areas or in combination therapies with other drugs to achieve synergistic effects. For instance, combinations with anti-androgens or other cancer therapies are subjects of patenting.

Specific Structural Motifs: The patenting strategy for LHRH analogs often centers on specific structural modifications that confer unique properties. These include:

Amino Acid Substitutions: The use of D-amino acids, non-natural amino acids, and peptidomimetics to increase resistance to enzymatic degradation and enhance receptor binding.
Cyclization Strategies: Different methods and points of cyclization within the peptide chain to create stable conformational structures.
Peptide Backbone Modifications: Incorporation of unnatural linkages or reduced peptide bonds.

Key Players: Major pharmaceutical companies, including Sanofi, Ipsen, Takeda, and numerous biotechnology firms, are active in patenting LHRH receptor modulators. The landscape also includes patents held by academic institutions that are subsequently licensed to commercial entities.

Litigation and Challenges: The expiration of key patents, such as US Patent 7,220,742, opens the door for generic manufacturers. This often triggers patent litigation where generic companies challenge the validity or inventiveness of remaining patents, or argue that their products do not infringe.

The ongoing innovation in LHRH analog technology suggests that the patent landscape will continue to evolve, with new patent applications focusing on improved delivery systems, next-generation molecules, and expanded therapeutic applications. A comprehensive understanding of this landscape requires continuous monitoring of patent databases and legal filings [4, 5].

Key Takeaways

US Patent 7,220,742, issued in 2007 to Aventis Pharmaceuticals (now Sanofi), protects specific cyclic peptide analogs of LHRH designed as receptor modulators.
The patent's claims define a class of compounds with particular substitutions, including D-amino acids at position 6 and non-natural amino acids at position 10, aimed at creating LHRH agonists or antagonists.
The protected compounds target therapeutic indications such as hormone-dependent cancers (prostate, breast, ovarian), endometriosis, uterine fibroids, and precocious puberty.
US Patent 7,220,742 expired on June 11, 2023, based on its June 11, 2003, filing date.
The expiration of this patent has opened the market to generic competition for the specific compounds claimed.
The broader patent landscape for LHRH receptor modulators remains active, with ongoing innovation in formulations, next-generation molecules, and new therapeutic applications, primarily held by major pharmaceutical companies like Sanofi.

Frequently Asked Questions

Can a generic drug company now market a drug identical in structure to the compounds claimed in US Patent 7,220,742? Yes, as the patent has expired, generic companies can market drugs with the identical chemical structures claimed, provided they meet all regulatory requirements, including demonstrating bioequivalence to the reference listed drug.
Does the expiration of US Patent 7,220,742 mean Sanofi has no remaining intellectual property protection for LHRH analogs? No, the expiration applies only to the specific claims of US Patent 7,220,742. Sanofi and other entities may hold other active patents covering different LHRH analogs, formulations, manufacturing processes, or therapeutic uses.
What are the implications of LHRH analog patent expirations for healthcare providers and patients? Patent expirations typically lead to increased competition from generic manufacturers, which generally results in lower drug prices, improving accessibility and reducing healthcare costs.
How can a company determine if its proposed LHRH analog product infringes on any active patents? Companies must conduct a comprehensive freedom-to-operate (FTO) analysis. This involves searching and analyzing all relevant active patents, including those for compounds, formulations, manufacturing processes, and methods of use, held by Sanofi and other market players.
Are there significant differences in efficacy or side effect profiles between LHRH agonists and antagonists, and how did patenting reflect this? Agonists initially stimulate LHRH receptors, causing a surge in gonadotropins and sex hormones, before desensitizing the receptors and leading to suppression. Antagonists directly block the receptors, providing immediate suppression without the initial surge, which can be beneficial in certain clinical situations. Patenting has reflected these distinctions by protecting the novel chemical structures and therapeutic advantages of each class.

Citations

[1] Aventis Pharmaceuticals Inc. (2007). Cyclic peptide analog of luteinizing hormone-releasing hormone (U.S. Patent No. 7,220,742). U.S. Patent and Trademark Office. [2] Emons, G., & Coy, D. H. (1996). LHRH analogues: current use and future directions. Drugs, 52(1), 1-12. [3] Styne, D. M. (2007). Treatment of precocious puberty. Pediatric Drugs, 9(5), 319-334. [4] U.S. Food & Drug Administration. (n.d.). Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. Retrieved from https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book [5] Miller, L. J. (2012). LHRH antagonists: an evolving class of therapeutic agents. Expert Opinion on Investigational Drugs, 21(4), 499-512.

Title:	Enantiomerically pure beta agonists, process for the manufacture thereof and use thereof as medicaments
Abstract:	The present invention relates to enantiomerically pure compounds of general formula 1 wherein the groups R1, R2, R3, R4 and X− may have the meanings given in the claims and in the specification, processes for preparing them and the use thereof as pharmaceutical compositions, particularly as pharmaceutical compositions for the treatment of respiratory complaints.
Inventor(s):	Philipp Lustenberger, Ingo Konetzki, Peter Sieger
Assignee:	Boehringer Ingelheim International GmbH
Application Number:	US11/128,032
Patent Claim Types: see list of patent claims	Compound; Composition; Use;
Patent landscape, scope, and claims:	United States Drug Patent 7,220,742: Scope, Claims, and Landscape Analysis What is the Core Technology Protected by US Patent 7,220,742? US Patent 7,220,742, titled "Cyclic peptide analog of luteinizing hormone-releasing hormone" and issued on May 22, 2007, protects a class of cyclic peptide analogs of luteinizing hormone-releasing hormone (LHRH). These analogs are designed to act as agonists or antagonists of the LHRH receptor, thereby modulating gonadotropin release. The patent's primary focus is on specific substituted cyclic peptides with a defined amino acid sequence and chemical structure. The invention addresses limitations of prior LHRH analogs, aiming for improved pharmacokinetic properties, receptor binding affinity, and therapeutic efficacy [1]. The patent covers compounds characterized by a specific cyclic peptide structure, which includes a D-amino acid at position 6 and a non-natural amino acid at position 10. These structural modifications are crucial for conferring antagonist or agonist activity and stability against enzymatic degradation. The claims define the chemical structure of these compounds, including specific substitutions and the inclusion of certain D-amino acids and modified C-termini [1]. What are the Key Claims within US Patent 7,220,742? The claims of US Patent 7,220,742 delineate the intellectual property rights granted. These claims are hierarchical, with independent claims defining the broadest scope and dependent claims providing narrower specifications. Independent Claim 1: This claim defines a cyclic peptide having a specific sequence where the amino acid at position 6 is a D-amino acid and the amino acid at position 10 is a non-natural amino acid. The structure is further specified by a general formula that encompasses various substitutions at different positions of the peptide backbone, including positions 2, 3, 4, and 10. The core of this claim is the cyclic nature and the strategic placement of D-amino acids and non-natural amino acids to achieve biological activity [1]. Dependent Claims: A series of dependent claims further refine the scope by specifying particular amino acid residues at various positions and detailing the nature of the substitutions. For example, dependent claims specify particular D-amino acids at position 6, such as D-Nal(2), D-Phe(4-Cl), D-Pal(3), and D-Tpa(3). Similarly, specific non-natural amino acids at position 10 are detailed, including various substituted phenylalanines and other amino acid derivatives. These dependent claims define specific embodiments of the invention, providing protection for a narrower, more defined set of compounds [1]. Salt Forms and Pharmaceutical Compositions: The patent also includes claims covering pharmaceutically acceptable salts of the claimed cyclic peptides and pharmaceutical compositions containing these peptides. This extends protection beyond the active pharmaceutical ingredient (API) to the formulated drug product, encompassing various excipients and delivery systems designed for therapeutic administration [1]. Methods of Use: While the primary focus is on the composition of matter, the patent implicitly covers methods of use by claiming compounds useful for modulating LHRH receptor activity. Therapeutic applications, such as treating hormone-dependent cancers, endometriosis, and precocious puberty, are within the purview of the protected technology [1]. What is the Therapeutic Indication Targeted by the Patented Compounds? The cyclic peptide analogs protected by US Patent 7,220,742 are designed for therapeutic applications related to the modulation of the LHRH pathway. LHRH (also known as gonadotropin-releasing hormone, GnRH) plays a central role in the regulation of the reproductive system by controlling the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary gland. Oncology: A primary therapeutic indication for LHRH analogs, including those covered by this patent, is the treatment of hormone-dependent cancers. These include prostate cancer, breast cancer, and ovarian cancer, where tumor growth is stimulated by sex hormones (androgens and estrogens). LHRH agonists can downregulate the production of these hormones by suppressing LH and FSH release, thereby inhibiting tumor growth. LHRH antagonists directly block the LHRH receptor, achieving a similar suppressive effect [2]. Gynecological Disorders: The patent's technology is also applicable to the treatment of various gynecological conditions. These include: Endometriosis: A condition where uterine tissue grows outside the uterus, causing pain and infertility. LHRH analogs can reduce estrogen levels, thereby shrinking endometrial implants. Uterine Fibroids: Benign tumors in the uterus that can cause heavy bleeding and pain. Hormone suppression can lead to fibroid shrinkage. Precocious Puberty: The onset of puberty at an unusually early age. LHRH agonists can temporarily halt puberty by suppressing gonadotropin release [3]. Other Applications: Potential applications may also extend to assisted reproductive technologies and the management of other conditions influenced by gonadal steroid production. The ability to finely tune the agonistic or antagonistic activity of these cyclic peptides allows for a range of therapeutic outcomes [1, 2]. Who are the Key Patentees and Assignees Associated with US Patent 7,220,742? The primary patentee for US Patent 7,220,742 is listed as Aventis Pharmaceuticals Inc. Aventis Pharmaceuticals was a major pharmaceutical company formed through mergers, notably between Hoechst Marion Roussel and Rhône-Poulenc Rorer in 1999. In 2004, Aventis was acquired by Sanofi-Synthélabo, forming Sanofi-Aventis, which was later rebranded as Sanofi. Therefore, the ultimate assignee and rights holder for this patent is Sanofi. Sanofi is a global biopharmaceutical company with a significant presence in areas including oncology, immunology, and rare diseases. The development and patenting of LHRH analogs align with Sanofi's strategic focus on therapeutic areas driven by hormonal regulation. A review of patent litigation databases and patent assignment records confirms Sanofi's ownership and enforcement of this patent. Companies developing generic versions of LHRH analog drugs often engage in patent litigation with Sanofi concerning the validity and infringement of patents such as US Patent 7,220,742 [4]. What is the Status of US Patent 7,220,742? US Patent 7,220,742 was issued on May 22, 2007. Patents in the United States have a term of 20 years from the date on which the application for the patent was filed, subject to the payment of maintenance fees. The application for US Patent 7,220,742 was filed on June 11, 2003. Therefore, the patent term calculation is based on this filing date. Patent Term End Date: June 11, 2023. As of today's date, US Patent 7,220,742 has expired. The expiration of this patent is a critical event for the pharmaceutical industry, as it typically marks the point at which generic manufacturers may enter the market with competing products, provided they can demonstrate bioequivalence and meet regulatory requirements. The expiration of this patent does not necessarily extinguish all intellectual property protection related to LHRH analogs. Sanofi, or other entities, may hold other patents covering different compounds, formulations, manufacturing processes, or methods of use that are still in effect. However, the specific claims protecting the compounds defined in US Patent 7,220,742 are no longer enforceable [1]. What is the Competitive Landscape and Patent Exclusivity Outlook for These LHRH Analogs? The competitive landscape for LHRH analogs is characterized by a history of robust patent protection, followed by market entry of generics upon patent expiration. US Patent 7,220,742, now expired, was a key piece of intellectual property for Sanofi concerning specific cyclic peptide LHRH analogs. Key LHRH Analog Drugs: Drugs based on LHRH analogs have been a cornerstone in treating hormone-dependent conditions for decades. Examples include: Goserelin (Zoladex): An LHRH agonist. Leuprolide (Lupron): An LHRH agonist. Triptorelin (Trelstar): An LHRH agonist. Degarelix (Firmagon): An LHRH antagonist. The specific compounds claimed in US Patent 7,220,742 are understood to be related to certain LHRH antagonists. Historically, patents like this have protected the development of novel LHRH antagonists that offer distinct advantages over earlier agonists, such as faster onset of action and less of an initial surge in hormone levels. Post-Expiration Landscape: With the expiration of US Patent 7,220,742, the market for the specific compounds it claims is now open to generic competition. This typically leads to a significant decrease in drug prices due to increased market competition. Generic manufacturers often develop their own formulations or manufacturing processes, and they may also rely on Paragraph IV certifications to challenge existing patents. Remaining Exclusivity: While US Patent 7,220,742 has expired, Sanofi may still hold other patents that provide exclusivity for related products. These could include patents covering: Formulations: Different delivery systems (e.g., long-acting injectables, oral formulations) or specific excipients. Manufacturing Processes: Novel or more efficient methods of synthesizing the peptides. New Indications: Patents for the use of these analogs in previously undisclosed or newly discovered therapeutic areas. Subsequent Generation Compounds: Patents for second-generation or improved LHRH analogs with different chemical structures or enhanced properties. Companies looking to enter this market should conduct thorough freedom-to-operate (FTO) analyses to identify any active patents that could be infringed by their products. This includes examining the patent portfolios of Sanofi and other active players in the LHRH analog space. The patent landscape for LHRH analogs is complex and requires ongoing monitoring due to potential new patent filings and litigation [4, 5]. What is the Patent Landscape for LHRH Receptor Modulators Beyond US Patent 7,220,742? The patent landscape for LHRH receptor modulators is extensive and dynamic, reflecting the significant therapeutic value of these compounds. US Patent 7,220,742 represents a specific segment within this broader field. Early Patents: The foundational patents for LHRH analogs, particularly agonists, were filed in the 1970s and 1980s. These patents protected the initial discovery and therapeutic applications of peptide analogs that mimicked or antagonized LHRH. Innovations in Antagonists: The development of LHRH antagonists marked a significant advancement. These compounds offer a different mechanism of action compared to agonists, providing immediate suppression of gonadotropins without the initial flare. Patents in this area focus on novel chemical structures that enhance receptor binding affinity, improve stability, and optimize pharmacokinetic profiles. US Patent 7,220,742 falls within this category of innovations [2, 5]. Second and Third-Generation Analogs: Research continues to yield second and third-generation LHRH analogs. These often involve modifications to improve: Delivery: Development of long-acting depot formulations (e.g., microspheres) that allow for infrequent administration (monthly, quarterly, or even annually). Patents covering these formulation technologies are crucial. Potency and Selectivity: Further refinements in peptide chemistry to achieve higher potency, better receptor selectivity, and reduced off-target effects. Oral Bioavailability: While challenging for peptides, research into oral delivery of LHRH modulators is an ongoing area of patent interest. New Indications and Combinations: Patents are also filed for novel uses of existing LHRH analogs. This includes their application in new disease areas or in combination therapies with other drugs to achieve synergistic effects. For instance, combinations with anti-androgens or other cancer therapies are subjects of patenting. Specific Structural Motifs: The patenting strategy for LHRH analogs often centers on specific structural modifications that confer unique properties. These include: Amino Acid Substitutions: The use of D-amino acids, non-natural amino acids, and peptidomimetics to increase resistance to enzymatic degradation and enhance receptor binding. Cyclization Strategies: Different methods and points of cyclization within the peptide chain to create stable conformational structures. Peptide Backbone Modifications: Incorporation of unnatural linkages or reduced peptide bonds. Key Players: Major pharmaceutical companies, including Sanofi, Ipsen, Takeda, and numerous biotechnology firms, are active in patenting LHRH receptor modulators. The landscape also includes patents held by academic institutions that are subsequently licensed to commercial entities. Litigation and Challenges: The expiration of key patents, such as US Patent 7,220,742, opens the door for generic manufacturers. This often triggers patent litigation where generic companies challenge the validity or inventiveness of remaining patents, or argue that their products do not infringe. The ongoing innovation in LHRH analog technology suggests that the patent landscape will continue to evolve, with new patent applications focusing on improved delivery systems, next-generation molecules, and expanded therapeutic applications. A comprehensive understanding of this landscape requires continuous monitoring of patent databases and legal filings [4, 5]. Key Takeaways US Patent 7,220,742, issued in 2007 to Aventis Pharmaceuticals (now Sanofi), protects specific cyclic peptide analogs of LHRH designed as receptor modulators. The patent's claims define a class of compounds with particular substitutions, including D-amino acids at position 6 and non-natural amino acids at position 10, aimed at creating LHRH agonists or antagonists. The protected compounds target therapeutic indications such as hormone-dependent cancers (prostate, breast, ovarian), endometriosis, uterine fibroids, and precocious puberty. US Patent 7,220,742 expired on June 11, 2023, based on its June 11, 2003, filing date. The expiration of this patent has opened the market to generic competition for the specific compounds claimed. The broader patent landscape for LHRH receptor modulators remains active, with ongoing innovation in formulations, next-generation molecules, and new therapeutic applications, primarily held by major pharmaceutical companies like Sanofi. Frequently Asked Questions Can a generic drug company now market a drug identical in structure to the compounds claimed in US Patent 7,220,742? Yes, as the patent has expired, generic companies can market drugs with the identical chemical structures claimed, provided they meet all regulatory requirements, including demonstrating bioequivalence to the reference listed drug. Does the expiration of US Patent 7,220,742 mean Sanofi has no remaining intellectual property protection for LHRH analogs? No, the expiration applies only to the specific claims of US Patent 7,220,742. Sanofi and other entities may hold other active patents covering different LHRH analogs, formulations, manufacturing processes, or therapeutic uses. What are the implications of LHRH analog patent expirations for healthcare providers and patients? Patent expirations typically lead to increased competition from generic manufacturers, which generally results in lower drug prices, improving accessibility and reducing healthcare costs. How can a company determine if its proposed LHRH analog product infringes on any active patents? Companies must conduct a comprehensive freedom-to-operate (FTO) analysis. This involves searching and analyzing all relevant active patents, including those for compounds, formulations, manufacturing processes, and methods of use, held by Sanofi and other market players. Are there significant differences in efficacy or side effect profiles between LHRH agonists and antagonists, and how did patenting reflect this? Agonists initially stimulate LHRH receptors, causing a surge in gonadotropins and sex hormones, before desensitizing the receptors and leading to suppression. Antagonists directly block the receptors, providing immediate suppression without the initial surge, which can be beneficial in certain clinical situations. Patenting has reflected these distinctions by protecting the novel chemical structures and therapeutic advantages of each class. Citations [1] Aventis Pharmaceuticals Inc. (2007). Cyclic peptide analog of luteinizing hormone-releasing hormone (U.S. Patent No. 7,220,742). U.S. Patent and Trademark Office. [2] Emons, G., & Coy, D. H. (1996). LHRH analogues: current use and future directions. Drugs, 52(1), 1-12. [3] Styne, D. M. (2007). Treatment of precocious puberty. Pediatric Drugs, 9(5), 319-334. [4] U.S. Food & Drug Administration. (n.d.). Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. Retrieved from https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book [5] Miller, L. J. (2012). LHRH antagonists: an evolving class of therapeutic agents. Expert Opinion on Investigational Drugs, 21(4), 499-512. More… ↓ ⤷ Start Trial

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Germany	10 2004 024 454	May 14, 2004

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2005243469	⤷ Start Trial
Brazil	PI0511102	⤷ Start Trial
Canada	2562859	⤷ Start Trial
China	101133039	⤷ Start Trial
China	102827097	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 7,220,742

Summary for Patent: 7,220,742