US 12527771

US patent 12527771, titled "Viral inhibitors, the synthesis thereof, and intermediates thereto," was assigned to Takeda Pharmaceutical Co Ltd. The inventors listed are Jeffrey Scott DEPUE, Suresh Kumar Tipparaju, Helge Alfred REISCH, Datong Tang, and Kishore Ramachandran. The patent has a filing date of July 7, 2025, and was issued on January 20, 2026.

Abstract:
The patent describes methods for preparing maribavir, or its pharmaceutically acceptable salts. These methods include novel synthesis and purification techniques for maribavir intermediates, as well as new methods for purifying maribavir itself. The disclosure also covers compositions of maribavir, or its pharmaceutically acceptable salts, which contain reduced or low levels of impurities, and methods for treating viral infections using maribavir.

Independent Claims Overview:

• Independent Claim 1: This claim outlines a method for preparing a compound of Formula 2 (an intermediate for maribavir). It involves combining a compound of Formula 5 and a compound of Formula 6 in a specific amount of solvent (between 1.0 L/kg and 10.0 L/kg of Compound 5). The mixture is then heated to a temperature (T7) between approximately 90° C. and 110° C. and maintained at this temperature for 12 to 20 hours. Formulas 5, 6, and 2 are defined with specific R1 (optionally substituted C1-6 aliphatic, carbocyclyl, heterocyclyl, phenyl, or heteroaryl) and R2 (halogen) groups.
• Independent Claim 8: This claim details a method for preparing a compound of Formula 3 (another maribavir intermediate). It involves combining the compound of Formula 2 (as defined in claim 1) and a compound of Formula 8 in a solvent amount between 1.0 L/kg and 10.0 L/kg of Compound 2. The reaction mixture is heated to a temperature (T1) between approximately 90° C. and 110° C. and held for 12 to 20 hours to yield the compound of Formula 3. R1 and R2 are defined as in Claim 1, PG1 is a suitable oxygen protecting group, and X represents a salt of compound 3a.
• Independent Claim 12: This claim describes a method for preparing maribavir itself, or a pharmaceutically acceptable salt thereof. It involves combining the compound of Formula 3 (as defined in Claim 8) and a compound of Formula 4 in a solvent amount between 5.0 L/kg and 10.0 L/kg of Compound 3. The mixture is heated to a temperature (T4) between approximately 50° C. and 70° C. and maintained for 1 to 5 hours to produce maribavir. R1 and R2 are defined as in Claim 1, and PG1 is a suitable oxygen protecting group.

CAFC 2026 Dockets:
As of April 26, 2026, no dockets specifically related to US12527771 have been found in the CAFC 2026 dockets. However, there are two related cases filed in the New Jersey District Court: 2:26-cv-04939 and 2:26-cv-04121. The patent also notes that the "First worldwide family litigation filed" is linked via Darts-ip.

US patent 12527771 is involved in known litigation. The details available from the provided patent information are as follows:

1. Case 1

   • Plaintiff(s): Not specified in the provided text.
   • Defendant(s): Not specified in the provided text.
   • Jurisdiction: New Jersey District Court
   • Case Number: 2:26-cv-04939
   • Filing Date: Not explicitly stated in the provided text, but the case number indicates a 2026 filing year.
   • Outcome or Current Status: Filed

2. Case 2

   • Plaintiff(s): Not specified in the provided text.
   • Defendant(s): Not specified in the provided text.
   • Jurisdiction: New Jersey District Court
   • Case Number: 2:26-cv-04121
   • Filing Date: Not explicitly stated in the provided text, but the case number indicates a 2026 filing year.
   • Outcome or Current Status: Filed

Additionally, the patent family for US patent 12527771 is noted to have "First worldwide family litigation filed." Specific details regarding the parties, jurisdiction, case number, or status for this worldwide family litigation as it pertains directly to US12527771 are not provided in the given patent text.

Proceedings overview

There are no AIA trial proceedings on file for US patent 12527771 as of the most recent ingest. No web search results were found for any additional or older proceedings. This means the patent's claims remain untested by AIA trial proceedings, offering no immediate defensive posture based on PTAB invalidation.

Strategic summary

All claims of US12527771 are currently untested by AIA trial proceedings. This means that a defendant being asserted against still has all prior-art grounds available for challenging the patent's validity, as no estoppel has been triggered under § 315(e)(2). The absence of PTAB activity could suggest several things: the patent is relatively new, it hasn't been heavily asserted yet, or potential challengers have opted for other avenues to address its validity.

Recommended next steps

As there is no PTAB activity for US patent 12527771, a defendant facing assertion of this patent would need to initiate a new AIA trial proceeding if they wish to challenge its validity at the PTAB.

Inventors

• Jeffrey Scott DEPUE
• Suresh Kumar Tipparaju
• Helge Alfred REISCH
• Datong Tang
• Kishore Ramachandran

All inventors were employed by Takeda Pharmaceutical Co Ltd at the time of filing.

Original assignee

Takeda Pharmaceutical Co Ltd. Takeda Pharmaceutical Co Ltd is a global pharmaceutical company that develops, manufactures, and sells a range of pharmaceutical products. Their primary line of business is the research, development, manufacturing, and marketing of pharmaceutical drugs. They ship products embodying the claims, specifically LIVTENCITYTM (maribavir), which is an antiviral medication for CMV. Takeda Pharmaceutical Co Ltd is currently an operating company.

Assignment timeline

• 2025-08-13 (executed) / recorded 2025-08-13 — Reel 059905/0091
  • Conveyance: ASSIGNMENT OF ASSIGNOR'S INTEREST
  • Assignor: RAMACHANDRAN, KISHORE; DEPUE, JEFFREY SCOTT; REISCH, HELGE ALFRED; TIPPARAJU, SURESH KUMAR; TANG, DATONG
  • Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED
  • Correspondent: GILLIS, ALISON M., TAKEDA PHARMACEUTICALS INTERNATIONAL, INC., 95 HAYDEN AVENUE, LEXINGTON, MA 02421
  • Context: Transfer of inventor interests to the assignee

The USPTO Assignment Center search at https://assignmentcenter.uspto.gov/ shows no further recorded assignments for US patent 12527771 as of 2026-05-30.

Timeline diagram

timeline
    title Ownership of US 12527771
    2025 : Application filed by Takeda
    2025 : Inventor interests assigned to Takeda
    2026 : Patent granted to Takeda

NPE / troll-pattern signals

1. Shell-entity transfer — not present. The patent remains with Takeda Pharmaceutical Co Ltd, an operating company that commercializes products related to the patent.
2. Known asserter in the chain — not present. Takeda Pharmaceutical Co Ltd is not a known NPE.
3. Repeat correspondent across the chain — not present. Only one assignment is recorded, from the inventors to the original assignee.
4. Cascading transfers — not present. Only one assignment is recorded.
5. Pre-litigation transfer — unclear. While there are litigation cases related to this patent family (US case filed in New Jersey District Court, 2:26-cv-04939 and 2:26-cv-04121), the only recorded assignment is from the inventors to the original assignee, which occurred before these cases were filed (2025-08-13 vs. 2026 filings). There is no transfer to a separate entity directly preceding litigation for this specific patent.
6. Bankruptcy fire-sale — not present. Takeda Pharmaceutical Co Ltd is an active, operating company.
7. Privateering — not present. There is no indication of a transfer to an NPE for assertion on Takeda's behalf.
8. Defensive aggregator (anti-NPE) — not present. The patent remains with Takeda Pharmaceutical Co Ltd.

Verdict

Operating-company assertion

The patent remains assigned to Takeda Pharmaceutical Co Ltd, which is an active pharmaceutical company that ships a product embodying the claims (LIVTENCITYTM). While litigation exists for this patent family, it is being asserted by the original operating company, not a separate NPE.

USPTO Assignment Center search for US12527771

US Patent 12527771, titled "Viral inhibitors, the synthesis thereof, and intermediates thereto," references several U.S. patents as prior art. These references provide context for the invention, particularly concerning the synthesis and polymorphic forms of maribavir.

The identified prior art references and their potential anticipatory scope are detailed below. It is important to note that without the specific claims of US12527771, the assessment of anticipation under 35 U.S.C. § 102 is based on the general description of the invention in US12527771 and the summary provided for the cited prior art.

Most Relevant Prior Art for US12527771

1. U.S. Pat. No. 6,617,315

   • Full Citation: US 6,617,315 B1, "Ribofuranosylbenzimidazoles"
   • Publication/Filing Date: Granted September 9, 2003 (Application filed: December 14, 2001).
   • Brief Description: This patent discloses an alternative synthetic route for 2-(alkylamino)-1H-benzimidazoles, including steps for using 1-cyclohexyl-3-(2-morpholinoethyl) carbodiimide metho-p-toluenesulfonate as a desulfurizing agent, coupling 2-(alkylamino)-1H-benzimidazoles with 1,2,3,5-tri-O-acetyl-ribofuranose, and subsequent deprotection. It specifically details the synthesis of the acetyl-protected intermediate of maribavir in Scheme 3, Examples 24 and 25. The present patent (US12527771) explicitly states that the '315 patent does not exemplify the deacetylation of 5,6-dichloro-2-(isopropylamino)-1-(2,3,5-tri-O-acetyl-betal-L-ribofuranosyl)-1H-benzimidazole to afford maribavir.
   • Potential Anticipation: This patent potentially anticipates claims in US12527771 related to earlier steps in the synthesis of maribavir, particularly the formation of the benzimidazole core and its coupling with protected ribofuranose, as well as the acetyl-protected intermediate compound. Any claims in US12527771 covering these specific intermediate compounds or the methods of their preparation, as disclosed in US 6,617,315, could be anticipated. However, it does not anticipate the final deacetylation step to yield maribavir itself.

2. U.S. Pat. No. 6,482,939

   • Full Citation: US 6,482,939 B1, "Crystal forms of a benzimidazole riboside"
   • Publication/Filing Date: Granted November 19, 2002 (Application filed: November 15, 2001).
   • Brief Description: This patent discloses a particular polymorphic form of maribavir, specifically Form VI. US12527771 refers to this patent when discussing methods of preparing maribavir in Form VI, free of other crystal forms, solvates, or hydrates, and also for solid oral formulations comprising maribavir polymorphic Form VI with particular particle size distributions.
   • Potential Anticipation: This patent potentially anticipates claims in US12527771 directed to maribavir in its Form VI polymorphic form, pharmaceutical compositions comprising maribavir Form VI, and methods for preparing maribavir in Form VI, especially if such claims describe the physical form itself or compositions containing it without significant novel process steps or impurity profiles not found in the '939 patent. Claims related to specific particle size distributions of Form VI, if not specifically taught or rendered obvious by US 6,482,939, might not be anticipated.

3. U.S. Pat. No. 8,546,344

   • Full Citation: US 8,546,344 B2, "Processes for preparing crystalline maribavir"
   • Publication/Filing Date: Granted October 1, 2013 (Application filed: January 30, 2013).
   • Brief Description: This patent is cited in US12527771 as describing "other polymorphic forms" of maribavir, alongside US 6,482,939 and US 11,130,777, in the context of providing compositions comprising maribavir substantially free of these other polymorphic forms.
   • Potential Anticipation: This patent potentially anticipates claims in US12527771 that broadly cover other polymorphic forms of maribavir, their compositions, or general processes for their preparation. The significance for US12527771 lies in differentiating its "substantially free of other polymorphic forms" claims from what is taught in US 8,546,344.

4. U.S. Pat. No. 11,130,777

   • Full Citation: US 11,130,777 B2, "CRYSTALLINE MARIBAVIR FORM A"
   • Publication/Filing Date: Granted September 28, 2021 (Application filed: May 11, 2021).
   • Brief Description: Similar to US 8,546,344, this patent is cited in US12527771 as describing "other polymorphic forms" of maribavir, indicating it relates to different crystalline forms of the compound.
   • Potential Anticipation: This patent potentially anticipates claims in US12527771 that cover specific polymorphic forms of maribavir (e.g., Form A as indicated by the title of '777 patent), compositions containing them, or methods of their manufacture. US12527771 differentiates itself by aiming for compositions substantially free of the forms described in this patent.

Obviousness Analysis under 35 U.S.C. § 103 for US Patent 12527771

A person having ordinary skill in the art (PHOSITA) in the field of pharmaceutical synthesis, particularly process chemistry for antiviral compounds like maribavir, would possess knowledge of standard synthetic methodologies, reaction optimization techniques, and purification strategies. This includes familiarity with common solvents, catalysts, protecting groups, and methods for improving yield, purity, and scalability of chemical processes.

The primary prior art reference for this analysis is U.S. Pat. No. 6,617,315 (hereafter, the '315 patent), which is explicitly identified in the present patent as disclosing aspects of maribavir synthesis. Other references, U.S. Pat. Nos. 6,482,939, 8,546,344, and 11,130,777, relate to polymorphic forms of maribavir, which are downstream product characteristics rather than the synthetic methods claimed in the independent claims.

The present patent (US12527771) generally frames its invention as providing an "improved synthesis of maribavir" with "increased overall yield" and "reduced and/or low levels of impurities," particularly when scaling up the synthesis. This objective of improving an existing synthetic process is a routine motivation for a PHOSITA in process chemistry.

Independent Claim 1: Method for Preparing Compound 2

Claim 1 describes a method for preparing a compound of Formula 2 (an intermediate for maribavir) by combining a compound of Formula 5 and a compound of Formula 6 in a solvent amount between 1.0 L/kg and 10.0 L/kg of Compound 5. The mixture is heated to a temperature (T7) between approximately 90° C. and 110° C. and maintained for 12 to 20 hours. R1 and R2 groups are broadly defined.

• Prior Art Teaching: The '315 patent explicitly "discloses an alternative route: synthesis of 2-(alkylamino)-1H-benzimidazoles," which are generic to Compound 2a and thus encompass Compound 2 as claimed in US12527771. This demonstrates that the fundamental chemical transformation to produce Compound 2 was known in the art prior to the present invention.
• Motivation to Combine/Modify: A PHOSITA, faced with the known synthesis of 2-(alkylamino)-1H-benzimidazoles from the '315 patent, would be routinely motivated to optimize the reaction conditions to achieve a higher yield, improved purity, or greater efficiency, especially when considering large-scale pharmaceutical manufacturing. The present patent itself states, "the present invention encompasses the recognition that the synthesis of maribavir can be modified to increase the overall yield." Such optimization would naturally involve adjusting parameters like solvent volume, reaction temperature, and reaction time.
• Predictability/Routine Nature of Modification: The specific ranges claimed for the solvent amount (1.0 L/kg to 10.0 L/kg), temperature (90° C. to 110° C.), and reaction time (12 to 20 hours) fall within the bounds of routine experimentation typically performed by a PHOSITA to optimize a known chemical reaction. Exploring these ranges to find optimal conditions for yield and purity is a standard practice in process development. For example, the patent notes that "a lower volume of reaction solvent e.g., 1,4-dioxane" can be used, implying optimization of solvent usage.

Independent Claim 8: Method for Preparing Compound 3

Claim 8 details a method for preparing a compound of Formula 3 (another maribavir intermediate) by combining the compound of Formula 2 (as defined in Claim 1) and a compound of Formula 8 in a solvent amount between 1.0 L/kg and 10.0 L/kg of Compound 2. The reaction mixture is heated to a temperature (T1) between approximately 90° C. and 110° C. and held for 12 to 20 hours to yield the compound of Formula 3. R1 and R2 are defined as in Claim 1, PG1 is a suitable oxygen protecting group, and X represents a salt of compound 3a.

• Prior Art Teaching: The '315 patent teaches the "coupling 2-(alkylamino)-1H-benzimidazoles [Compound 2] with 1,2,3,5-tri-O-acetyl-ribofuranose [Compound 8]" to produce an acetyl-protected intermediate, which is generic to Compound 3a and thus encompasses Compound 3 (when PG1 is acetyl). The '315 patent therefore describes the core chemical transformation.
• Motivation to Combine/Modify: A PHOSITA would be motivated to optimize the coupling reaction conditions described in the '315 patent to improve the yield and purity of the intermediate Compound 3, which is critical for the overall efficiency of maribavir synthesis. The present patent explicitly recognizes that "certain reagents (and amounts thereof) and/or reaction conditions may provide improved quality compound 3, or a salt thereof (e.g., with higher purity and/or minimal byproducts), and/or improve the yield and/or purity of compound 3, or a salt thereof." Additionally, the incorporation of crystallization, including salt formation, to purify intermediates is a well-established technique in pharmaceutical chemistry to achieve desired purity profiles and facilitate isolation.
• Predictability/Routine Nature of Modification: Similar to Claim 1, the claimed ranges for solvent amount (1.0 L/kg to 10.0 L/kg), temperature (90° C. to 110° C.), and reaction time (12 to 20 hours) are parameters commonly optimized through routine experimentation by a PHOSITA. The use of "a salt" (X) for compound 3a is also a routine practice for improving crystallization and purification of organic compounds. The patent states that "incorporation of a crystallization (e.g., comprising salt formation) into Step 2 may improve the yield and/or reduce the formation of byproducts," confirming that this is an optimization of a known synthetic route.

Independent Claim 12: Method for Preparing Maribavir

Claim 12 describes a method for preparing maribavir, or a pharmaceutically acceptable salt thereof, by combining the compound of Formula 3 (as defined in Claim 8) and a compound of Formula 4 in a solvent amount between 5.0 L/kg and 10.0 L/kg of Compound 3. The mixture is heated to a temperature (T4) between approximately 50° C. and 70° C. and maintained for 1 to 5 hours to produce maribavir. PG1 is a suitable oxygen protecting group.

• Prior Art Teaching: The '315 patent discloses the "deprotection of 2-(alkylamino)-1-(2,3,5-tri-O-acetyl-beta-L-ribofuranosyl-1H-benzimidazoles" to yield maribavir. While the present patent states that the '315 patent "does not exemplify deacetylation... to afford maribavir," the general concept of deprotection of the protected intermediate (Compound 3) to obtain maribavir is clearly taught. Compound 4 would represent the deprotecting agent used in this step.
• Motivation to Combine/Modify: A PHOSITA would be motivated to complete the synthesis of maribavir from the known protected intermediate (Compound 3) by performing the deprotection step, as described generally in the '315 patent. Optimization of this final step is essential to ensure high yield and purity of the active pharmaceutical ingredient.
• Predictability/Routine Nature of Modification: The selection of suitable deprotecting agents (represented by Compound 4) and the optimization of reaction conditions (solvent amount between 5.0 L/kg and 10.0 L/kg, temperature between 50° C. and 70° C., and reaction time between 1 and 5 hours) for deprotection of an acetyl-protected ribofuranosyl derivative are routine tasks for a PHOSITA. These parameters are commonly varied in process development to achieve efficient and high-quality product formation.

Conclusion on Obviousness

The independent claims of US12527771, directed to methods for preparing maribavir and its intermediates, would likely be considered obvious over U.S. Pat. No. 6,617,315. The '315 patent teaches the core synthetic pathway, including the formation of Compound 2, Compound 3, and the deprotection to maribavir. A PHOSITA, motivated to develop a more efficient, higher-yielding, and purer manufacturing process for a known pharmaceutical compound, would routinely explore and optimize the reaction parameters (e.g., solvent volumes, temperatures, reaction times, and purification methods like crystallization and salt formation) that are claimed in US12527771. The specific ranges and conditions claimed, while potentially representing an optimized process, do not appear to present unexpected results that would overcome the strong prima facie case of obviousness arising from the known synthetic route and the routine nature of process optimization.