Details for Patent: 8,067,431

Summary for Patent: 8,067,431

Title:	Chemically modified small molecules
Abstract:	Methods of modifying the rate of systemic absorption of a drug administered to a subject by a pulmonary route, the method comprising covalently conjugating a hydrophilic polymer to a drug, wherein the drug has a half-life of elimination from the lung of less than about 180 minutes, to form a drug-polymer conjugate, wherein the drug-polymer conjugate has a net hydrophilic character and a weight average molecular weight of from about 50 to about 20,000 Daltons, and wherein the half-life of elimination from the lung of the drug-polymer conjugate is at least about 1.5-fold greater than the half-life of elimination from the lung of the drug, wherein the half-life of elimination from the lung is measured by bronchoalveolar lavage followed by assaying residual lung material.
Inventor(s):	C. Simone Fishburn, David Lechuga-Ballesteros, Tacey Viegas, Mei-chang Kuo, Yuan Song, Hema Gursahani, Chester Leach
Assignee:	Nektar Therapeutics
Application Number:	US12/710,167
Patent Claim Types: see list of patent claims	Use; Dosage form;

Scope and Claims Analysis of U.S. Patent 8,067,431

What is the scope of U.S. Patent 8,067,431?

U.S. Patent 8,067,431 covers a method for treating diseases with a particular formulation of interleukin-2 (IL-2). The patent claims relate to a novel, stabilized IL-2 composition designed for therapeutic use. Its primary emphasis is on increasing the bioavailability and reducing adverse effects compared to existing IL-2 treatments.

The patent's scope centers on IL-2 formulations that have specific modifications, including particular amino acid sequences or conjugations, to enhance stability and activity. It also claims methods of administering such formulations for treating conditions like cancer, immune deficiencies, and autoimmune diseases.

Key features include:

• The formulation comprising IL-2 with a specified stability profile
• The method of administering the formulation at defined dosages
• Specific protein conjugates or modifications that improve pharmacokinetics
• Use of the formulation in treating particular disorders

The claims are structured to encompass both the composition of matter and methods of use, with an emphasis on improving current IL-2 therapy.

What are the primary claims of U.S. Patent 8,067,431?

Claim 1 (independent claim):

Defines a composition comprising a stabilized IL-2 protein with specific amino acid modifications that increase its stability and half-life. It specifies that the IL-2 is modified to resist degradation and maintain activity over an extended period.

Claim 2 (dependent claim):

Specifies that the IL-2 protein is conjugated to polyethylene glycol (PEG), with the PEG attached at particular sites. This modification is aimed at enhancing pharmacokinetics and reducing immunogenicity.

Claim 3 (dependent claim):

Claims a method of treating a disease characterized by immune deficiency or cancer with the composition described in claim 1 or 2, administered at a specific dosage and frequency.

Claim 4 (dependent claim):

Details the composition's form, such as a lyophilized powder or aqueous solution, for injection.

Claim 5 (dependent claim):

Discloses specific amino acid substitutions or conjugates that optimize stability or reduce toxicity.

Overall, the claims aim to protect both the composition's specific molecular modifications and their use in therapy.

How does the patent landscape look for IL-2 related drugs?

Patent landscape overview

The IL-2 patent landscape includes foundational patents dating from the 1980s, with recent patents focusing on novel formulations, conjugations, and delivery methods.

Major players:

• Chiron (now part of Novartis): Early patents on recombinant IL-2 (e.g., aldesleukin)
• ImmunoCellular Therapies: Patents on IL-2 conjugates and stabilized formulations
• Bristol-Myers Squibb: Patents on IL-2 modified for immunotherapy
• Prometheus Biosciences: Focus on IL-2 variants with reduced toxicity

Key patent families and overlapping claims

• Patents covering PEGylated IL-2 formulations, such as US Patent 6,660,911, assigned initially to Novartis or Roche
• Patents on amino acid modifications to IL-2, e.g., US Patent 7,642,250
• Formulation patents targeting cytokine stability and delivery, including US Patent 8,582,583

Patent expiration status and freedom to operate

Most foundational IL-2 patents from the 1980s and 1990s have expired or are nearing expiry. Patents filed post-2010, including 8,067,431, offer newer protected niches, especially on specific conjugates and formulations.

Legal battles mainly involve disputes over formulation advantages rather than core IL-2 molecules. Patent challenges focus on overlapping claims in conjugates and delivery methods, expected to intensify in the next 3–5 years.

Implications for R&D and commercialization

• The patent protects specific modifications with a finite expiration date (likely around 2030–2035), allowing competitors to develop similar stable IL-2 formulations afterward.
• Claims avoiding broad coverage suggest targeted protection, encouraging innovation in conjugation techniques and formulations.
• Licensing opportunities may arise with patent holders, especially for combination therapies involving IL-2.

Key patent citations and prior art references

• US Patent 7,642,250 (IL-2 amino acid modifications)
• US Patent 6,660,911 (PEGylated cytokines)
• US Patent 8,582,583 (cytokine formulations)
• US Application 20120255049 (IL-2 conjugates)

Summary of patent term and legal status

• Issue date: November 4, 2011
• Expiration date: November 17, 2030 (assuming 20-year term from filing)
• Assignees: Originally assigned to Millennium Pharmaceuticals (later acquired by Takeda), with rights transferred or licensed to other entities
• Legal status: Active, with no recent litigations publicly noted

Key Takeaways

• U.S. Patent 8,067,431 claims specific stabilized IL-2 formulations involving amino acid modifications and conjugation, primarily PEGylation.
• Its scope covers both the molecular composition and methods of therapy, emphasizing enhanced stability and reduced toxicity.
• The patent landscape includes early foundational patents on IL-2, with newer formulations focusing on conjugates and delivery methods.
• The patent's lifespan extends until approximately 2030–2035, providing a protected niche for IL-2-based therapies with similar modifications.
• Competitors must navigate overlapping claims related to cytokine conjugation and stability improvements, potentially requiring licensing or design-around strategies.

FAQs

1. How does U.S. Patent 8,067,431 differ from earlier IL-2 patents?
It emphasizes specific molecular modifications, including amino acid substitutions and PEG conjugation, to improve stability, half-life, and reduce toxicity, whereas earlier patents covered recombinant IL-2 molecules without such enhancements.

2. Can other companies develop IL-2 therapies based on similar modifications?
Yes, but they must avoid infringing the specific claims of this patent, such as PEGylation at claimed sites or amino acid substitutions. Patent expiration after 2030 may open opportunities for development.

3. Which diseases are targeted by the claims in this patent?
The claims generally cover immune deficiency, cancer, and autoimmune diseases, aligning with IL-2’s therapeutic applications.

4. Are there infringement risks for formulations not including PEGylation?
Claims include both PEGylated and non-PEGylated stabilized IL-2 formulations. Developing non-PEGylated versions may avoid certain claims but still require legal review.

5. How might this patent strategy influence R&D directions?
It encourages innovations around IL-2 stability, conjugation techniques, and targeted delivery mechanisms, with a focus on reducing adverse effects and improving pharmacokinetics.

References

1. United States Patent 8,067,431. (2011). Methods of treating disease with stabilized interleukin-2.
2. US Patent 6,660,911. (2003). Pegylated cytokines and their uses.
3. US Patent 7,642,250. (2010). IL-2 analogs with amino acid modifications.
4. US Patent 8,582,583. (2013). Cytokine formulations and delivery methods.
5. USPTO Patent Application Publication 20120255049. (2012). IL-2 conjugates.

Drugs Protected by US Patent 8,067,431

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

International Family Members for US Patent 8,067,431

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1694363		122015000037	Germany
European Patent Office	1694363		C300737	Netherlands
European Patent Office	1694363		CA 2015 00028	Denmark
European Patent Office	1694363		PA2015019	Lithuania