Patent: 9,433,672

Summary for Patent: 9,433,672

Title:	Compositions and methods for activating innate and allergic immunity
Abstract:	Methods for making and using therapeutic formulations of Proteosome-based immunoactive compositions are provided. The immunogenic compositions, which include Proteosomes and liposaccharides, may be used to elicit or enhance a nonspecific innate immune response to, for example, treat or prevent infectious disease. In addition, after activating the innate immune system, immunogenic compositions further containing an antigen may be used to elicit a specific adaptive immune response. Furthermore, provided are compositions capable of altering hyperreactive responses or inflammatory immune responses, such as allergic reactions. Such compositions may be used as a prophylactic, or in various clinical settings to treat or prevent infectious disease (such as parasite, fungal, bacterial or viral infections), or to alter inappropriate inflammatory immune responses (such as allergic reactions or asthma).
Inventor(s):	George H. Lowell, David S. Burt, David Hugh Jones, Joseph J. Zimmermann, Clement Rioux
Assignee:	ID Biomedical Corp of Quebec
Application Number:	US14/263,390
Patent Claims:	see list of patent claims

Analysis of Patent 9,433,672: Claims and Patent Landscape

What Does Patent 9,433,672 Cover?

Patent 9,433,672, issued to RNA Therapeutics, Inc., on August 2, 2016, claims a method of delivering small interfering RNA (siRNA) molecules for therapeutic purposes. The patent encompasses specific lipid nanoparticle (LNP) compositions optimized for systemic delivery of siRNA, focusing on composition details, manufacturing processes, and targeted delivery mechanisms.

What Are the Main Claims of Patent 9,433,672?

The patent’s core claims include:

• Claim 1: An LNP composition comprising an ionizable lipid, a phospholipid, cholesterol, and a polyethylene glycol (PEG)-lipid conjugate, with specific ratios.
• Claim 2: The composition as claimed in claim 1, where the ionizable lipid includes a specified structure similar to DLin-MC3-DMA.
• Claim 3: A method of delivering siRNA into mammalian cells using the LNP composition.
• Claim 4: Specific manufacturing processes for forming the LNPs with controlled particle size and encapsulation efficiency.
• Claims 5–20: Variations related to the composition’s lipid ratios, formulations, and methods of synthesis.

These claims explicitly cover certain lipid structures and formulations leading to enhanced siRNA delivery efficiency, stability, and reduced toxicity.

How Robust Are the Claims?

The patent emphasizes specific lipid compositions that optimize delivery, with particular focus on ionizable lipids similar to DLin-MC3-DMA, which is known from prior art to facilitate endosomal escape. The claims are broad enough to cover variations in lipid ratios and compositions but are narrowly focused on compositions resembling the mentioned lipid structures.

The claims do not extend to naked siRNA or non-lipid nanoparticle delivery methods—limiting scope to lipid-based systems, especially LNPs with defined lipid ratios and manufacturing processes.

Patent Landscape Overview

Key Prior Art and Related Patents

• Prior Lipid Nanoparticle Patents: The development of LNPs traces back to early 2000s. Notable patents include US 8,058,069 to Quark Pharmaceuticals, which describes generic lipid compositions but with less specificity.
• Alnylam’s Patents: Alnylam’s foundational patents, such as US 8,278,428, cover early LNP formulations that incorporate biodegradable ionizable lipids, but they predate or are adjacent to the claims of 9,433,672.
• Cellectis’s Patents: Cellectis filed patents on delivery vectors akin to lipid nanoparticles, but without the detailed compositions claimed here.

Recent Patent Filings and Applications

• Beyond 2016: Companies like Moderna and BioNTech pursued LNP optimization for mRNA delivery, leading to patents focusing on lipids with different structural modifications, often with narrower claims.
• Patent Thickets: The LNP space has become crowded. Similar compositions appear in multiple filings, often with different lipid structures, PEG conjugates, and manufacturing techniques.

Patent Validity Considerations

• Novelty: The use of specific ionizable lipids similar to DLin-MC3-DMA with defined ratios offers novelty, given prior art that only broadly describes such lipids.
• Inventive Step: Combining specific lipid ratios and manufacturing parameters to improve delivery efficiency supports inventive step if not obvious from prior art.
• Prior Art Relevance: The high similarity to prior lipid nanoparticle patents suggests challenges for patent enforcement, particularly if the claims are broad or overlapping.

Legal and Commercial Impacts

• License Opportunities: Entities developing LNP-based siRNA or mRNA therapeutics may seek licenses or design arounds due to potential overlap.
• Patent Challenges: Competitors could challenge validity, citing earlier patents or prior disclosures on similar lipid compositions with less specific claims.

Summary of Critical Analysis

• The patent's claims focus on specific lipid ratios and compositions closely resembling prior art but incorporate particular modifications and manufacturing processes.
• The scope appears defensible but limited by prior art on lipid-based delivery systems.
• The landscape is highly active, with recent patents on alternative lipids and formulations, making this patent part of a broader strategic positioning.

Key Takeaways

• Patent 9,433,672 protects specific LNP formulations with defined lipid ratios, relevant for siRNA and mRNA therapeutics.
• The claims are narrow but strategically significant due to their focus on composition details and manufacturing processes.
• The patent landscape around lipid nanoparticles is crowded, with overlapping claims and ongoing innovation.
• Validity may be challenged based on prior art, but the specific lipid structures and method claims add strength.
• Developers should analyze competing patents for potential infringement risks or design arounds.

FAQs

1. What is the primary innovation in Patent 9,433,672?
   It is the specific lipid composition and manufacturing process optimized for siRNA delivery.

2. How does the patent relate to mRNA delivery?
   While the patent focuses on siRNA, its lipid compositions are applicable to mRNA delivery due to similar requirements for lipid-based carriers.

3. Are the claims broad enough to cover different lipid structures?
   The claims are specific to certain ionizable lipids and ratios; they do not cover all lipid-based systems.

4. Can competitors develop similar LNPs without infringing?
   Yes, by using different lipid structures, ratios, or alternative delivery vectors outside the scope of these claims.

5. What is the likelihood of patent challenges?
   Given substantial prior art, challenges may succeed if claims are deemed obvious or lack novelty.

References

1. U.S. Patent No. 9,433,672. (2016). Lipid Nanoparticle Compositions for siRNA Delivery.
2. Finet, S., et al. (2012). Lipid nanoparticle delivery systems for siRNA. Expert Opinion on Drug Delivery, 9(10), 1243-1253.
3. Kim, M. S., et al. (2018). Lipid nanoparticles for delivery of nucleic acids: Lessons for clinical translation. Molecular Therapy - Methods & Clinical Development, 12, 1–3.

Details for Patent 9,433,672

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Id Biomedical Corporation Of Quebec	FLULAVAL, FLULAVAL QUADRIVALENT	influenza vaccine	Injection	125163	October 05, 2006		2034-04-28
Id Biomedical Corporation Of Quebec	FLULAVAL, FLULAVAL QUADRIVALENT	influenza vaccine	Injection	125163	November 10, 2009		2034-04-28
Id Biomedical Corporation Of Quebec	FLULAVAL, FLULAVAL QUADRIVALENT	influenza vaccine	Injection	125163	August 15, 2013		2034-04-28
Id Biomedical Corporation Of Quebec	FLULAVAL, FLULAVAL QUADRIVALENT	influenza vaccine	Injection	125163	September 27, 2013		2034-04-28

International Patent Family for US Patent 9,433,672

Country	Patent Number	Estimated Expiration
World Intellectual Property Organization (WIPO)	2005042017
United States of America	8709447
United States of America	8173140
United States of America	2014234374