Prior art

To identify the most relevant prior art for US patent 8,685,998, I will examine the patent citations listed on the Google Patents page for US8685998B2.

Prior Art References for US Patent 8,685,998:

The patent lists several "Patent citations" and "Non-patent citations" as prior art. I will focus on the patent citations first.

Here are some of the key prior art patent citations, along with their details and potential anticipation:

• EP-A-0 184 162

  • Full Citation: EP-A-0 184 162
  • Publication/Filing Date: While the exact filing date is not immediately available from the provided text, the patent states that the "preparation of tacrolimus is described in EP-A-0 184 162". This indicates it predates US8685998.
  • Brief Description: This patent describes the preparation of tacrolimus itself.
  • Potential Anticipation (35 U.S.C. § 102): This reference would likely anticipate any claims directed solely to the compound tacrolimus, as it describes its preparation. However, US8685998 claims methods of treatment using specific extended-release formulations and pharmacokinetic profiles, which EP-A-0 184 162 would not inherently disclose.
  • Relevant Claims: Potentially relevant to the novelty of tacrolimus as an active substance within the claimed formulations, but not directly to the method claims (1, 8, 13) which focus on the extended-release formulation and its therapeutic effects in de novo transplant patients.

• EP-A-0 444 659

  • Full Citation: EP-A-0 444 659
  • Publication/Filing Date: Not immediately available from the provided text, but explicitly cited as prior art for tacrolimus analogues.
  • Brief Description: This patent discloses analogues of tacrolimus.
  • Potential Anticipation (35 U.S.C. § 102): Similar to EP-A-0 184 162, this reference would anticipate claims broadly covering tacrolimus analogues themselves. It would not, however, anticipate the specific extended-release formulations or method of treatment claims of US8685998.
  • Relevant Claims: Potentially relevant to the novelty of using specific tacrolimus analogues within the claimed formulations, but not directly to claims 1, 8, or 13, which are focused on method of treatment with an extended release formulation.

• U.S. Pat. No. 6,387,918

  • Full Citation: U.S. Pat. No. 6,387,918
  • Publication/Filing Date: Not immediately available from the provided text, but cited for tacrolimus analogues.
  • Brief Description: This patent also discloses analogues of tacrolimus.
  • Potential Anticipation (35 U.S.C. § 102): Similar to the European patents mentioned above, this patent would anticipate claims related to the chemical structure of tacrolimus analogues, but not the specific extended-release dosage forms, release profiles, or method of treatment claims of US8685998.
  • Relevant Claims: Potentially relevant to the novelty of using specific tacrolimus analogues, but not directly to claims 1, 8, or 13.

• WO 2005/020993

  • Full Citation: WO 2005/020993
  • Publication/Filing Date: The patent explicitly states "Inventors of the present application have in the patent application WO 2005/020993 also tested different formulations of tacrolimus". This indicates it predates US8685998 and shares inventors.
  • Brief Description: This patent application describes tacrolimus formulations, including both fast and slow-release tablets, demonstrating improved bioavailability compared to Prograf®. It links improved bioavailability to tacrolimus being in a dissolved state in the dosage form. The patent explicitly states it "additionally describe tacrolimus compositions by use of the technology and with extended release formulations thereof".
  • Potential Anticipation (35 U.S.C. § 102): This reference is highly relevant. It discloses extended-release formulations of tacrolimus and improved bioavailability, which are core concepts in US8685998. Depending on the specific release profiles and de novo patient treatment methods detailed in WO 2005/020993, it could potentially anticipate aspects of claims 1, 8, and 13, particularly regarding the concept of extended-release tacrolimus for improved bioavailability. The specific in-vitro dissolution criteria (less than 50% released after 10 hours) and the precise systemic exposure percentages for de novo patients would need careful comparison to determine direct anticipation. It might render these claims obvious if the differences are not sufficiently inventive.
  • Relevant Claims: Potentially anticipates or renders obvious claims 1, 8, and 13 due to its disclosure of extended-release tacrolimus formulations with improved bioavailability.

• WO 2005/020994

  • Full Citation: WO 2005/020994
  • Publication/Filing Date: The patent states it's "by the same inventors relating to solid dispersions comprising tacrolimus," indicating it predates US8685998.
  • Brief Description: This patent application relates to solid dispersions comprising tacrolimus, further supporting the idea of improved bioavailability through dissolved tacrolimus.
  • Potential Anticipation (35 U.S.C. § 102): This reference is also highly relevant as it addresses the formulation aspect of tacrolimus in a dissolved state within a solid dispersion, which is a mechanism described in US8685998 for achieving extended release and improved bioavailability. It could potentially anticipate or render obvious the underlying formulation technology that enables the extended release described in claims 1, 8, and 13.
  • Relevant Claims: Potentially anticipates or renders obvious aspects of claims 1, 8, and 13 related to the formulation of tacrolimus to achieve improved bioavailability through solid dispersions.

• WO99/49863

  • Full Citation: WO99/49863
  • Publication/Filing Date: Not explicitly stated, but described as "referred to above and owned by Fujisawa Pharmaceutical Co. (now Astellas) who developed Prograf®," indicating it significantly predates US8685998.
  • Brief Description: This patent describes the fast-release conventional product Prograf®, which comprises tacrolimus in a physical mixture of HPMC, lactose, and croscarmellose sodium.
  • Potential Anticipation (35 U.S.C. § 102): This reference would serve as a baseline for the conventional, immediate-release tacrolimus. It clearly describes a different release profile than the extended-release claimed in US8685998 and would therefore not anticipate the extended-release aspects. However, it is a crucial reference for establishing the background art against which the "improved" aspects of US8685998 are measured (e.g., increased bioavailability, decreased Cmax, improved pharmacokinetic profiles compared to Prograf®).
  • Relevant Claims: While not directly anticipating the extended-release features, it is the primary reference against which the "improvement" claims of 1, 8, and 13 are compared. The distinct release profile of Prograf® (fast release) highlights the novelty of the extended release of US8685998.

General Considerations for Anticipation:

For a prior art reference to anticipate a claim under 35 U.S.C. § 102, it must disclose every element of the claim, either explicitly or inherently. When dealing with method-of-treatment claims, especially those involving pharmacokinetic parameters and specific patient populations (like de novo transplant patients), the comparison must be very precise. A prior art reference that describes a tacrolimus formulation or even an extended-release formulation, but does not explicitly teach the specific in-vitro release profile (e.g., less than 50% released after 10 hours) and the specific systemic exposure percentages (e.g., at least 50% or 70% of immediate-release Prograf® for de novo patients, or at least 100% of a faster extended-release for de novo kidney patients) would likely not directly anticipate claims 1, 8, or 13. However, such references, especially WO 2005/020993 and WO 2005/020994, could be strong candidates for rendering the claims obvious under 35 U.S.C. § 103 if a person of ordinary skill in the art would have been motivated to combine or modify the prior art to achieve the claimed invention with a reasonable expectation of success.