Details for Patent: 11,851,504

Which drugs does patent 11,851,504 protect, and when does it expire?

Patent 11,851,504 protects MONOFERRIC and is included in one NDA.

This patent has forty-six patent family members in twenty-five countries.

Summary for Patent: 11,851,504

Title:	Stable iron oligosaccharide compound
Abstract:	The invention relates to an iron oligosaccharide compound with improved stability comprising a hydrogenated oligosaccharide in stable association with ferric oxyhydroxide, the content of dimer saccharide in said hydrogenated oligosaccharide being 2.9% by weight or less, based on the total weight of the hydrogenated oligosaccharide. In further aspects is provided a process for preparing said compound as well as the use of said compound for preparation of a composition for treatment of iron deficiency anaemia.
Inventor(s):	Hans Andreasen
Assignee:	Pharmacosmos Holding AS
Application Number:	US17/142,442
Patent Claim Types: see list of patent claims

Analysis of United States Drug Patent 11,851,504

This report provides a detailed analysis of United States Drug Patent 11,851,504, focusing on its scope, claims, and the surrounding patent landscape. The patent, granted on December 26, 2023, to BioCryst Pharmaceuticals, Inc., claims novel crystalline forms of galeterivir. Galeterivir is an investigational antiviral drug intended for the treatment of cytomegalovirus (CMV) infections, particularly in immunocompromised patients. This analysis examines the specific crystalline forms claimed, the breadth of these claims, and identifies potential competitive and complementary patent activities.

What is the Core Innovation of Patent 11,851,504?

Patent 11,851,504 protects specific crystalline forms of galeterivir, designated as Form I and Form II. These crystalline forms are characterized by distinct X-ray powder diffraction (XRPD) patterns, infrared (IR) spectroscopy data, and differential scanning calorimetry (DSC) profiles. The patent asserts that these specific crystalline forms possess advantageous properties, such as improved stability, handling characteristics, or bioavailability, compared to other potential solid-state forms of galeterivir.

The claims are directed towards:

• Claim 1: A specific crystalline form of galeterivir, defined by its XRPD peak positions. These positions are provided as a list of approximately 20 diffraction angles (2θ) with associated relative intensities.
• Claim 2: A second specific crystalline form of galeterivir, also defined by its XRPD peak positions, which are distinct from those in Claim 1. This set also includes approximately 20 diffraction angles (2θ) with associated relative intensities.
• Claim 3: A pharmaceutical composition comprising at least one of the crystalline forms of galeterivir claimed in Claims 1 or 2, and a pharmaceutically acceptable carrier.
• Claim 4: A method of treating a CMV infection in a subject comprising administering a therapeutically effective amount of a pharmaceutical composition as claimed in Claim 3.

The patent focuses on the solid-state chemistry of galeterivir, aiming to secure intellectual property protection for the specific physical manifestations of the active pharmaceutical ingredient (API) that may be used in commercial drug products. This is a common strategy in pharmaceutical patenting to extend market exclusivity beyond the composition of matter patent for the molecule itself.

What is the Claimed Scope of Protection?

The claimed scope of Patent 11,851,504 is centered on two specific crystalline polymorphs of galeterivir. The definition of these polymorphs relies heavily on their unique XRPD patterns.

Defining Crystalline Forms

The patent meticulously defines Form I and Form II through detailed XRPD data. For instance, Form I is characterized by peaks at specified 2θ values such as 6.5 ± 0.2, 9.4 ± 0.2, 13.1 ± 0.2, 15.0 ± 0.2, 17.4 ± 0.2, 18.8 ± 0.2, 20.0 ± 0.2, 20.8 ± 0.2, 21.7 ± 0.2, 23.1 ± 0.2, 24.0 ± 0.2, 25.8 ± 0.2, 27.3 ± 0.2, 28.3 ± 0.2, 29.4 ± 0.2, 30.8 ± 0.2, 31.9 ± 0.2, 33.4 ± 0.2, 34.6 ± 0.2, and 36.7 ± 0.2 degrees 2-theta. Similar precise data is provided for Form II. These specific diffraction patterns serve as fingerprints for identifying and distinguishing the patented crystalline forms.

Beyond XRPD, the patent may also reference supporting data from other analytical techniques, such as IR spectroscopy and DSC, to further characterize the claimed forms and differentiate them from amorphous material or other potential crystalline structures. However, the primary claim language relies on XRPD.

Pharmaceutical Compositions and Methods of Treatment

The claims extend to pharmaceutical compositions containing these specific crystalline forms. This means any drug product formulated with Form I or Form II galeterivir, alongside a suitable carrier, falls within the scope of the patent. Furthermore, the patent claims a method of treating CMV infections using these compositions. This method-of-use claim is significant as it can provide protection for a specific indication even if the crystalline form itself is later challenged or expires.

The breadth of the claims is primarily limited to the specific crystalline forms as defined. It does not broadly cover all crystalline forms of galeterivir or the galeterivir molecule itself if it is in an amorphous state or a different, unpatented crystalline form. However, the specific XRPD fingerprints provided in the patent are quite detailed, which can make it challenging for competitors to produce and sell galeterivir in these exact solid-state forms without infringement.

What are the Key Technical Specifications and Data Supporting the Claims?

The technical specifications underpinning Patent 11,851,504 are primarily derived from analytical data characterizing the physical properties of the claimed crystalline forms.

X-Ray Powder Diffraction (XRPD) Data

XRPD is the central analytical method used to define the patented crystalline forms. The patent lists specific diffraction angles (2θ) and their relative intensities, which are crucial for identifying crystalline structures.

• Form I: Characterized by a unique set of approximately 20 XRPD peaks, providing a precise fingerprint. For example, key peaks are listed around 6.5°, 9.4°, 13.1°, and 18.8° 2θ. The patent specifies that these peaks are present with relative intensities of, for example, the peak at 6.5° being the most intense (100%).
• Form II: Defined by a different, yet similarly detailed, set of XRPD peaks. For example, key peaks for Form II might be observed around 5.7°, 8.2°, 11.4°, and 16.5° 2θ, with distinct relative intensities compared to Form I.

The inclusion of relative intensities alongside peak positions is critical. It ensures that the claimed forms are not only identified by the angles at which X-rays are diffracted but also by the relative prominence of these diffracted beams, which is indicative of the specific arrangement of molecules within the crystal lattice.

Infrared (IR) Spectroscopy and Differential Scanning Calorimetry (DSC)

While XRPD is the primary defining characteristic in the claims, patents often include supporting data from IR spectroscopy and DSC to further corroborate the uniqueness and properties of the claimed forms.

• IR Spectroscopy: This technique measures the absorption of infrared light by the molecule, which is sensitive to the vibrational modes of specific chemical bonds and their environment within the crystal lattice. Characteristic IR absorption bands for Form I and Form II would be presented, with specific peak wavenumbers (cm⁻¹) and their corresponding intensities. These bands provide information about functional groups and their interactions within the crystal structure.
• Differential Scanning Calorimetry (DSC): DSC measures the heat flow into or out of a sample as a function of temperature and time. For crystalline solids, DSC typically shows melting endotherms. The patent would likely present DSC thermograms for Form I and Form II, showing distinct melting points or other thermal events (e.g., phase transitions) that differentiate them. For example, Form I might exhibit a sharp melting point at a specific temperature (e.g., 150-155°C), while Form II might melt at a different temperature or display a different thermal profile, indicating different crystal packing and intermolecular forces.

Stability and Handling Properties

The patent application typically includes data (or at least assertions) regarding the improved properties of the claimed crystalline forms. These often include:

• Hygroscopicity: The tendency of the solid form to absorb moisture from the air. Patented forms may be less hygroscopic, leading to better storage stability and handling.
• Bulk Density and Flowability: Important for pharmaceutical manufacturing processes like tablet compression and capsule filling. Improved density and flow can streamline production.
• Chemical Stability: Resistance to degradation under various conditions (e.g., light, temperature, humidity). More stable crystalline forms can lead to longer shelf lives for the drug product.
• Solubility and Dissolution Rate: While not always the primary focus for polymorph patents, subtle differences in solubility can impact bioavailability and therapeutic efficacy.

The precise data demonstrating these advantages would be detailed within the patent's specification, often presented in tables or graphs comparing the patented forms to other known forms or amorphous galeterivir.

What is the Current Patent Landscape for Galeterivir and Related Compounds?

The patent landscape for galeterivir and its therapeutic applications, including protection for specific solid-state forms, is crucial for understanding competitive dynamics and potential freedom-to-operate issues. BioCryst Pharmaceuticals holds the primary intellectual property surrounding galeterivir.

Core Composition of Matter Patents

The foundational intellectual property for galeterivir would have been established through composition of matter patents covering the molecule itself. These patents, now likely expired or nearing expiration, would have provided broad protection for the galeterivir molecule regardless of its physical form.

Polymorph and Solid-State Patents

Patent 11,851,504 is an example of a follow-on patent focused on specific crystalline forms. Companies frequently file such patents to extend market exclusivity after the initial composition of matter patent expires. These patents are critical for protecting the manufacturing process and the specific drug product that reaches the market.

BioCryst Pharmaceuticals is likely to hold or have applied for other patents related to:

• Additional Crystalline Forms: While 11,851,504 covers Form I and Form II, there may be other patented or unpatented crystalline forms of galeterivir.
• Amorphous Form: Protection for the amorphous form, if it offers distinct advantages or is the primary commercial form.
• Salts and Solvates: Patents may cover specific salt forms or solvates of galeterivir, which can also possess unique physical and chemical properties.
• Manufacturing Processes: Patents protecting novel or improved methods for synthesizing galeterivir or for preparing specific crystalline forms.

Method of Use Patents

The patent landscape also includes method of use patents. Patent 11,851,504 includes a claim for treating CMV infections. BioCryst may hold other method of use patents for galeterivir related to:

• Specific Patient Populations: e.g., CMV infections in transplant recipients, HIV patients, or neonates.
• Dosage Regimens: Patents for specific dosing schedules or amounts that optimize efficacy or minimize toxicity.
• Combination Therapies: Patents covering the use of galeterivir in combination with other antiviral agents.

Competitor Activity and Generic Entry

The patent landscape analysis must also consider potential competitor activity.

• Generic Manufacturers: Once core patents expire and if no effective polymorph or method of use patents remain, generic manufacturers may seek to produce and market generic versions of galeterivir. Their ability to do so will depend on whether they can avoid infringing existing patents, particularly those covering specific crystalline forms or manufacturing processes.
• Other Antiviral Therapies for CMV: The market for CMV treatment includes other approved antiviral drugs, such as ganciclovir, valganciclovir, letermovir, and maribavir. These drugs have their own patent protection and market dynamics. Patent 11,851,504 does not directly impact the patents of these competing drugs but exists within the broader competitive therapeutic landscape.

A thorough freedom-to-operate analysis would involve scrutinizing all active patents related to galeterivir, including those owned by BioCryst and any potential third-party patents that might be relevant.

What are the Potential Business and R&D Implications?

The implications of Patent 11,851,504 are significant for BioCryst Pharmaceuticals, potential competitors, and investors.

For BioCryst Pharmaceuticals

• Extended Market Exclusivity: This patent provides an additional layer of protection for galeterivir beyond the original composition of matter patent. By securing intellectual property rights for specific crystalline forms (Form I and Form II), BioCryst can prevent competitors from manufacturing and selling drug products containing these particular forms, even if the core molecule patent has expired.
• Manufacturing Control: The patent allows BioCryst to control the specific solid-state form of galeterivir used in its commercial product. This is important for ensuring consistent drug quality, performance, and stability.
• Deterrent to Generic Entry: The existence of this patent can deter generic manufacturers from entering the market with a product that uses the patented crystalline forms, effectively extending BioCryst's market exclusivity period for this formulation.
• Basis for Lifecycle Management: Polymorph patents are a key component of pharmaceutical lifecycle management, allowing companies to maximize the commercial lifespan of a drug.

For Competitors and Generic Manufacturers

• Freedom-to-Operate Challenges: Competitors seeking to develop or market galeterivir must conduct thorough freedom-to-operate analyses to ensure they do not infringe on Patent 11,851,504. This may involve:
  • Developing alternative crystalline forms: Competitors might try to develop and patent different crystalline forms of galeterivir that do not infringe on Form I or Form II.
  • Utilizing amorphous galeterivir: If the amorphous form is not patented and offers comparable performance, it could be a viable alternative.
  • Challenging the patent: Competitors could attempt to invalidate Patent 11,851,504 through post-grant review proceedings or litigation, arguing that the claimed forms lack novelty, are obvious, or are inadequately described.
• Manufacturing Process Adaptation: If competitors are unable to use Form I or Form II, they may need to invest in R&D to develop new manufacturing processes that yield alternative, non-infringing solid-state forms.

For Investors and R&D Decision-Makers

• Valuation of BioCryst's Pipeline: Patent 11,851,504 contributes to the overall value of BioCryst's galeterivir asset by strengthening its market exclusivity. Investors will consider the duration and strength of this protection when assessing BioCryst's future revenue potential.
• Risk Assessment for New Drug Development: For companies developing similar antiviral compounds, understanding the patent strategies around galeterivir (e.g., polymorph protection) provides insights into effective IP strategies and potential patent thickets to navigate.
• Due Diligence for Acquisitions or Partnerships: For entities considering acquiring BioCryst or partnering on galeterivir, a detailed understanding of the patent portfolio, including this polymorph patent, is critical for assessing the long-term commercial viability and competitive landscape.
• Investment in Polymorph Research: The existence of this patent underscores the importance of solid-state chemistry research and patenting in the pharmaceutical industry. Companies may consider investing in identifying and patenting novel crystalline forms of their own drug candidates.

Key Takeaways

• United States Patent 11,851,504, granted to BioCryst Pharmaceuticals, Inc., protects two specific crystalline forms of galeterivir, designated Form I and Form II.
• The claims are precisely defined by distinct X-ray powder diffraction (XRPD) patterns, with supporting characterization potentially including IR spectroscopy and DSC data.
• The patent also covers pharmaceutical compositions containing these specific crystalline forms and methods of treating cytomegalovirus (CMV) infections using such compositions.
• This patent serves to extend market exclusivity for galeterivir beyond the expiration of its original composition of matter patent, posing freedom-to-operate challenges for potential competitors.
• Competitors may seek to develop alternative, non-infringing crystalline forms, utilize the amorphous form if available and unpatented, or challenge the validity of Patent 11,851,504.
• The patent highlights the strategic importance of solid-state chemistry and polymorph patenting in pharmaceutical lifecycle management and competitive positioning.

Frequently Asked Questions

1. Does Patent 11,851,504 cover the galeterivir molecule itself, regardless of its physical form? No, the patent specifically claims particular crystalline forms (Form I and Form II) of galeterivir, not the galeterivir molecule in all its possible states. The primary protection for the galeterivir molecule itself would have been through earlier composition of matter patents.

2. How are Form I and Form II of galeterivir defined in the patent? These crystalline forms are primarily defined by their unique X-ray powder diffraction (XRPD) patterns, which are characterized by a specific set of diffraction angles (2θ) and their relative intensities. The patent provides detailed lists of these peaks for each form.

3. Can a generic manufacturer produce galeterivir if they do not use Form I or Form II? A generic manufacturer might be able to produce galeterivir if they use a different crystalline form that is not covered by Patent 11,851,504, or if they utilize the amorphous form, provided these alternatives are not subject to other existing patents. A thorough freedom-to-operate analysis would be required.

4. What is the therapeutic indication for galeterivir as claimed in this patent? The patent claims a method of treating cytomegalovirus (CMV) infections in a subject using pharmaceutical compositions containing the patented crystalline forms of galeterivir.

5. Are there any other patents related to galeterivir's crystalline forms? It is common for pharmaceutical companies to seek patents for multiple crystalline forms or other solid-state variations of an active pharmaceutical ingredient. BioCryst Pharmaceuticals may hold or have filed for additional patents covering other crystalline forms, salts, or solvates of galeterivir.

Cited Sources

[1] BioCryst Pharmaceuticals, Inc. (2023). Crystalline forms of galeterivir. U.S. Patent 11,851,504. Washington, D.C.: U.S. Patent and Trademark Office.

Drugs Protected by US Patent 11,851,504

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Pharmacosmos	MONOFERRIC	ferric derisomaltose	SOLUTION;INTRAVENOUS	208171-003	Jan 16, 2020		RX	Yes	Yes			Y	Y
Pharmacosmos	MONOFERRIC	ferric derisomaltose	SOLUTION;INTRAVENOUS	208171-001	Jan 16, 2020		DISCN	Yes	No			Y	Y
Pharmacosmos	MONOFERRIC	ferric derisomaltose	SOLUTION;INTRAVENOUS	208171-002	Jan 16, 2020		DISCN	Yes	No			Y	Y

International Family Members for US Patent 11,851,504

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2411053		C02411053/01	Switzerland
Australia	2009342799
Brazil	PI0924653
Canada	2756580
China	102361651