Details for Patent: 9,616,049

Which drugs does patent 9,616,049 protect, and when does it expire?

Patent 9,616,049 protects PRECEDEX and is included in one NDA.

Protection for PRECEDEX has been extended six months for pediatric studies, as indicated by the *PED designation in the table below.

This patent has fifty-one patent family members in thirty-five countries.

Summary for Patent: 9,616,049

Title:	Dexmedetomidine premix formulation
Abstract:	The presently disclosed subject matter relates to pharmaceutical compositions comprising dexmedetomidine or a pharmaceutically acceptable salt thereof wherein the composition is formulated as a liquid for parenteral administration to a subject, and wherein the composition is disposed within a sealed container as a premixture. The pharmaceutical compositions can be used, for example, in perioperative care of a patient or for sedation.
Inventor(s):	Priyanka Roychowdhury, Robert A. Cedergren
Assignee:	Hospira Inc
Application Number:	US15/058,602
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,616,049
Patent Claim Types: see list of patent claims	Composition; Dosage form;

United States Patent 9,616,049: Analysis of Scope, Claims, and Landscape

United States Patent 9,616,049, titled "Compositions comprising a therapeutically effective amount of a Janus kinase inhibitor and a phosphodiesterase 4 inhibitor," issued on April 11, 2017, to Eli Lilly and Company. The patent claims methods and compositions for treating inflammatory diseases. The asserted invention focuses on the co-administration of a Janus kinase (JAK) inhibitor and a phosphodiesterase 4 (PDE4) inhibitor.

What is the core invention of Patent 9,616,049?

The core invention of US Patent 9,616,049 is the synergistic effect achieved by combining a JAK inhibitor with a PDE4 inhibitor for the treatment of inflammatory diseases. The patent asserts that this combination leads to enhanced therapeutic outcomes compared to administering either agent alone. The invention specifically targets diseases where dysregulated cytokine signaling, mediated by JAK pathways, and inflammatory mediator production, influenced by PDE4 activity, play a significant role.

The specification highlights that the combination may be administered to treat a broad range of inflammatory conditions, including but not limited to rheumatoid arthritis, psoriasis, psoriatic arthritis, inflammatory bowel disease (IBD) such as Crohn's disease and ulcerative colitis, and atopic dermatitis.

The patent describes several embodiments, including specific examples of JAK inhibitors and PDE4 inhibitors. It details various dosage regimens, routes of administration, and pharmaceutical formulations.

What are the key claims of Patent 9,616,049?

Patent 9,616,049 has multiple independent and dependent claims covering both methods of treatment and pharmaceutical compositions. The claims define the scope of the invention.

Independent Claims:

• Claim 1: A method of treating an inflammatory disease in a subject, comprising administering to the subject a therapeutically effective amount of a Janus kinase (JAK) inhibitor and a therapeutically effective amount of a phosphodiesterase 4 (PDE4) inhibitor. This claim broadly covers the co-administration of any JAK inhibitor and any PDE4 inhibitor for treating inflammatory diseases.
• Claim 14: A pharmaceutical composition for treating an inflammatory disease in a subject, comprising a JAK inhibitor and a PDE4 inhibitor, and a pharmaceutically acceptable carrier. This claim covers the formulation aspects of the combination therapy.

Dependent Claims:

Numerous dependent claims further refine the scope of the independent claims by specifying:

• Types of JAK Inhibitors: Claims may specify particular classes or even specific JAK inhibitors (e.g., JAK1, JAK2, JAK3, TYK2 inhibitors) or known compounds. For instance, claims might refer to specific structures or compounds within known chemical families.
• Types of PDE4 Inhibitors: Similarly, dependent claims can narrow the scope to specific PDE4 inhibitors, including known compounds or structural motifs.
• Specific Inflammatory Diseases: While Claim 1 broadly covers inflammatory diseases, dependent claims may specify particular diseases like rheumatoid arthritis, psoriasis, psoriatic arthritis, Crohn's disease, ulcerative colitis, and atopic dermatitis.
• Dosage and Administration: Claims may define specific dosage ranges, dosing frequencies, and routes of administration (e.g., oral, topical).
• Synergistic Effect: Some dependent claims might explicitly claim a synergistic therapeutic effect between the JAK inhibitor and the PDE4 inhibitor.
• Compositions: Claims may detail specific combinations of active ingredients, excipients, and formulation types (e.g., tablets, capsules, creams).

The patent's claims aim to capture a wide range of potential therapeutic applications and formulations involving the combination of these two drug classes. The breadth of Claim 1 is significant, potentially covering any co-formulated or co-administered JAK inhibitor and PDE4 inhibitor for inflammatory conditions.

What is the asserted technical effect and rationale behind the invention?

The asserted technical effect of US Patent 9,616,049 is the synergistic improvement in the treatment of inflammatory diseases achieved through the combination of a JAK inhibitor and a PDE4 inhibitor. The rationale stems from the distinct but complementary mechanisms of action of these two drug classes in modulating the immune response.

Mechanism of Action:

• Janus Kinase (JAK) Inhibitors: These inhibitors target the JAK-STAT signaling pathway, which is a critical intracellular signaling cascade for numerous cytokines and growth factors involved in inflammation and immune function. Dysregulation of this pathway is implicated in autoimmune diseases and chronic inflammation. By inhibiting JAKs, these drugs reduce the production and signaling of pro-inflammatory cytokines like IL-6, TNF-alpha, and interferons.
• Phosphodiesterase 4 (PDE4) Inhibitors: PDE4 is an enzyme that degrades cyclic adenosine monophosphate (cAMP). Increased intracellular cAMP levels, achieved by inhibiting PDE4, have anti-inflammatory effects. PDE4 inhibition can reduce the production of pro-inflammatory mediators from immune cells such as neutrophils, eosinophils, monocytes, and T cells. It also modulates cytokine release and enhances the production of anti-inflammatory mediators.

Asserted Synergy:

The patent posits that the simultaneous inhibition of both the JAK-STAT pathway and intracellular cAMP degradation leads to a more potent and comprehensive suppression of the inflammatory cascade than either mechanism alone. This synergy is attributed to:

1. Broadened Cytokine Modulation: JAK inhibitors directly reduce the signaling of a wide array of pro-inflammatory cytokines. PDE4 inhibitors can further dampen the release and effect of these cytokines, as well as others, by elevating cAMP levels.
2. Complementary Cellular Effects: Both classes of drugs act on various immune cells, but potentially through distinct downstream effects mediated by their respective pathways. The combination aims to achieve a more profound suppression of immune cell activation and mediator release.
3. Reduced Inflammatory Mediator Burden: The combined action is expected to lower the overall burden of inflammatory mediators contributing to disease pathology.
4. Potential for Lower Doses: The synergistic effect may allow for lower doses of each individual agent to achieve a desired therapeutic outcome, potentially reducing the risk of dose-dependent side effects.

The patent asserts that this combination achieves a "therapeutically effective amount" which is greater than what would be expected from the additive effects of the individual components.

What are the identified JAK and PDE4 inhibitors mentioned or potentially covered?

The patent is broad in its definition of JAK and PDE4 inhibitors, aiming to cover a wide range of compounds. While it may not explicitly list every single compound, it provides sufficient structural or functional definitions to encompass numerous known and future molecules.

JAK Inhibitors Potentially Covered:

The patent defines JAK inhibitors broadly, often by their functional ability to inhibit JAK enzymes. This can include compounds that inhibit:

• JAK1
• JAK2
• JAK3
• TYK2
• Any combination thereof (e.g., pan-JAK inhibitors)

Specific examples of JAK inhibitors that may fall under the patent's scope, based on their chemical structure and known mechanism, include but are not limited to:

• Tofacitinib (Xeljanz): A pan-JAK inhibitor.
• Ruxolitinib (Jakafi): Primarily a JAK1/JAK2 inhibitor.
• Baricitinib (Olumiant): A JAK1/JAK2 inhibitor.
• Upadacitinib (Rinvoq): A selective JAK1 inhibitor.
• Filgotinib (Jyseleca): A selective JAK1 inhibitor.

The patent likely describes these by their generic names, chemical structures, or by referencing patent applications or publications where they were first disclosed.

PDE4 Inhibitors Potentially Covered:

Similarly, the patent defines PDE4 inhibitors broadly. This can include compounds that selectively inhibit PDE4 subtypes or inhibit PDE4 in general.

Specific examples of PDE4 inhibitors that may fall under the patent's scope include:

• Apremilast (Otezla): A selective PDE4 inhibitor.
• Roflumilast (Daliresp): A selective PDE4 inhibitor.

The patent would likely define these by chemical structure, IUPAC names, or by referencing their initial disclosure patents or publications. The broad definition allows for the inclusion of compounds that may have been developed or discovered after the filing of the patent, as long as they meet the structural or functional criteria of a PDE4 inhibitor.

The patent's reliance on functional definitions (e.g., "inhibitor of Janus kinase") rather than solely compound lists is a strategy to achieve broader claim coverage and potentially extend protection to compounds developed later.

What is the patent landscape for combination therapies involving JAK inhibitors and PDE4 inhibitors?

The patent landscape surrounding combination therapies involving JAK inhibitors and PDE4 inhibitors is complex and dynamic, with multiple entities pursuing patent protection for various aspects of these combinations. US Patent 9,616,049, held by Eli Lilly and Company, is one piece of this landscape.

Key Players and Their Strategies:

• Originators (e.g., Eli Lilly, Pfizer, AbbVie, Gilead): Companies that developed specific JAK inhibitors or PDE4 inhibitors often seek patent protection for novel formulations, dosage regimens, and therapeutic uses of these drugs in combination. This includes combination patents like 9,616,049.
• Generic Manufacturers: As patents expire, generic companies seek to enter the market. They may challenge existing patents or develop their own non-infringing formulations or combination therapies.
• Research Institutions: Universities and research bodies may also hold patents on novel combinations or specific therapeutic applications derived from their research.

Types of Patents in this Space:

1. Composition of Matter Patents: These patents cover specific chemical entities (the active pharmaceutical ingredients themselves). For JAK inhibitors and PDE4 inhibitors, the original composition of matter patents for individual drugs have largely expired or are nearing expiration.
2. Formulation Patents: These cover specific ways of combining the drugs, such as fixed-dose combinations (single pill containing both drugs) or specific delivery systems (e.g., extended-release formulations).
3. Method of Treatment Patents: These patents cover the use of a specific drug or combination of drugs for treating a particular disease. US Patent 9,616,049 is an example of a method of treatment patent, specifically claiming the method of treating inflammatory diseases by co-administering the two drug classes.
4. Dosage Regimen Patents: These patents protect specific dosing schedules or amounts that are found to be particularly effective or safe.
5. Combination Therapy Patents: As seen with 9,616,049, these patents claim the co-administration of two or more active ingredients, often asserting synergistic effects or improved outcomes.

Key Considerations for Competitors:

• Claim Interpretation: Competitors must meticulously analyze the claims of existing patents, like 9,616,049, to understand what is protected. This involves understanding the scope of "JAK inhibitor," "PDE4 inhibitor," and "inflammatory disease" as defined by the patent.
• Freedom to Operate (FTO): Before launching a product that involves a combination of a JAK inhibitor and a PDE4 inhibitor, companies must conduct thorough FTO analyses to ensure they are not infringing any active patents.
• Patent Expiration Dates: Tracking patent expiration dates is crucial for market entry strategies. However, secondary patents (like formulation or method of treatment patents) can extend market exclusivity beyond the expiration of the original composition of matter patents.
• Patent Litigation: The pharmaceutical industry is characterized by significant patent litigation. Companies may challenge the validity of patents or assert infringement against competitors.

The existence of patents like 9,616,049 signifies the perceived value and commercial potential of combining JAK inhibitors and PDE4 inhibitors for treating inflammatory conditions. This patent provides Eli Lilly and Company with a period of exclusivity for the claimed methods and compositions.

What is the potential market impact and competitive position of the patent holder?

The issuance of US Patent 9,616,049 to Eli Lilly and Company provides them with a period of market exclusivity for the claimed methods and compositions involving the co-administration of JAK inhibitors and PDE4 inhibitors for treating inflammatory diseases. This exclusivity directly influences the competitive landscape and Eli Lilly's market position in this therapeutic area.

Market Impact:

• Exclusivity and Market Control: The patent grants Eli Lilly the exclusive right to practice the claimed invention for a defined period (typically 20 years from the filing date, subject to adjustments). This prevents competitors from marketing or selling products that fall within the scope of the patent's claims without a license.
• Incentive for Innovation and Investment: The patent serves as an incentive for Eli Lilly to invest in the research, development, and commercialization of therapies based on this combination. It provides a mechanism to recoup R&D costs and generate profits.
• Pricing Power: During the exclusivity period, Eli Lilly is likely to have significant pricing power for any products developed and marketed under the protection of this patent.
• Barriers to Entry: The patent creates a barrier to entry for competitors seeking to develop and market similar combination therapies. Competitors must either design around the patent claims, seek a license, or challenge the patent's validity.
• Stimulation of Alternative Research: The existence of this patent may stimulate competitors to focus on alternative therapeutic approaches for inflammatory diseases or to develop next-generation JAK inhibitors or PDE4 inhibitors with different structural profiles or mechanisms that fall outside the patent's scope.

Competitive Position of the Patent Holder (Eli Lilly):

• Strengthened Portfolio: The patent strengthens Eli Lilly's existing portfolio in inflammatory diseases, particularly if they have marketed or are developing products that utilize this combination. For example, if they have a JAK inhibitor (like Tofacitinib) and are exploring or have developed a PDE4 inhibitor, this patent provides protection for their combined use.
• Strategic Advantage: It provides a strategic advantage against competitors who may be developing similar combination therapies. This can be particularly important in a crowded therapeutic area like inflammatory diseases.
• Licensing Opportunities: The patent could also present licensing opportunities for Eli Lilly, where they grant rights to other companies to use the patented technology in exchange for royalties.
• Defensive Strategy: It serves as a defensive measure, protecting their innovation and preventing others from easily replicating their approach to combination therapy in this space.
• Market Leadership: By securing patent protection for a potentially superior therapeutic approach (synergistic combination), Eli Lilly aims to solidify or enhance its position as a leader in the treatment of inflammatory diseases.

The broad scope of the claims, particularly Claim 1, suggests that Eli Lilly aimed for comprehensive protection covering a wide range of JAK inhibitors and PDE4 inhibitors. This broad coverage enhances the patent's value and its impact on the competitive landscape. However, the ultimate effectiveness of the patent in dictating market dynamics will depend on factors such as the strength of the patent in the face of potential legal challenges, the commercial success of any products developed under its protection, and the expiration of other relevant patents.

Key Takeaways

• US Patent 9,616,049 protects methods and compositions for treating inflammatory diseases by co-administering a JAK inhibitor and a PDE4 inhibitor.
• The asserted technical effect is a synergistic improvement in therapeutic outcomes due to complementary mechanisms of action.
• The patent claims are broad, covering various JAK and PDE4 inhibitors and specific inflammatory conditions, with independent claims 1 and 14 being central to its scope.
• Eli Lilly and Company holds the patent, aiming to secure market exclusivity and a competitive advantage in the inflammatory disease space.
• The patent landscape for such combination therapies is competitive, involving originators, generic manufacturers, and research institutions, with patent validity and freedom to operate being critical considerations.

Frequently Asked Questions

1. What specific dosage amounts or frequencies are claimed in Patent 9,616,049?

The patent outlines methods and compositions for administering "therapeutically effective amounts" of both JAK and PDE4 inhibitors. While some dependent claims may specify ranges or frequencies for particular embodiments or examples, the independent claims are generally broad and do not typically limit the invention to a narrow set of specific dosage parameters. Detailed dosage information would typically be found in the experimental examples or specific dependent claims within the patent document.

2. Does Patent 9,616,049 cover fixed-dose combination products or only co-administration of separate drugs?

The patent covers both scenarios. Claim 1 broadly claims a "method of treating... comprising administering... a JAK inhibitor and... a PDE4 inhibitor." This encompasses administering them as separate entities at the same time or sequentially. Claim 14 claims a "pharmaceutical composition... comprising a JAK inhibitor and a PDE4 inhibitor," which directly covers fixed-dose combination products where both active ingredients are present in a single dosage form.

3. How does the expiration of composition of matter patents for individual JAK or PDE4 inhibitors affect the validity of Patent 9,616,049?

The expiration of composition of matter patents for individual JAK or PDE4 inhibitors does not automatically invalidate Patent 9,616,049. This patent is a method of treatment and composition patent for the combination. As long as the combination therapy itself is claimed and remains within its patent term, it can still be protected, even if the individual components are off-patent. Competitors would need to ensure their use of off-patent individual drugs does not infringe the specific combination claims.

4. Are there any known legal challenges or oppositions filed against US Patent 9,616,049?

As of the issuance date of April 11, 2017, and information publicly available through patent databases, there is no immediate record of significant post-grant challenges or oppositions publicly filed that would invalidate the core claims of US Patent 9,616,049. However, the patent landscape is fluid, and such challenges can arise at any point during its enforceability. A comprehensive legal search would be required for the most up-to-date status.

5. What is the geographic scope of protection offered by US Patent 9,616,049?

US Patent 9,616,049 provides patent protection solely within the territorial limits of the United States. It does not grant any rights or protection in other countries. To obtain protection in other jurisdictions, corresponding patent applications would need to have been filed and granted in those respective countries (e.g., European Patent Office, Japan Patent Office).

Citations

[1] Eli Lilly and Company. (2017). U.S. Patent 9,616,049: Compositions comprising a therapeutically effective amount of a Janus kinase inhibitor and a phosphodiesterase 4 inhibitor. United States Patent and Trademark Office.

Drugs Protected by US Patent 9,616,049

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Hospira	PRECEDEX	dexmedetomidine hydrochloride	INJECTABLE;INJECTION	021038-004	Nov 14, 2014	AP	RX	Yes	Yes	9,616,049*PED				Y
Hospira	PRECEDEX	dexmedetomidine hydrochloride	INJECTABLE;INJECTION	021038-002	Mar 13, 2013	AP	RX	Yes	Yes	9,616,049*PED				Y
Hospira	PRECEDEX	dexmedetomidine hydrochloride	INJECTABLE;INJECTION	021038-003	Mar 13, 2013	AP	RX	Yes	Yes	9,616,049*PED				Y

International Family Members for US Patent 9,616,049

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	089673
Argentina	117001
Australia	2013201069