Prior art — US Patent 8664239

To identify the most relevant prior art for US Patent 8,664,239, I will access the patent information directly from the USPTO database. This will allow me to examine the patent's cited references, which are typically the most pertinent prior art considered during examination.

Once I have the list of cited prior art, I will analyze each reference to provide its full citation, publication/filing date, a brief description, and which claims of US 8,664,239 it potentially anticipates under 35 U.S.C. § 102. Anticipation under 35 U.S.C. § 102 means that a single prior art reference discloses every element of a claimed invention, either explicitly or inherently.

The USPTO website provides a Patent Public Search tool which can be used to search for patents and their citations. I will use this tool to retrieve the necessary information.
To identify the most relevant prior art for US Patent 8,664,239, I need to access the patent's full text and its cited references from the USPTO database. Since I cannot directly interact with a live database, I will rely on the provided patent text to extract the cited references. The patent text itself explicitly lists several prior art documents.

From the provided full patent text, the following prior art references are explicitly mentioned and incorporated by reference:

EP-A-0 184 162: Cited for the preparation of tacrolimus.
EP-A-0 444 659: Cited for analogues of tacrolimus.
U.S. Pat. No. 6,387,918: Cited for analogues of tacrolimus.
WO99/49863 (Fujisawa Pharmaceutical Co.): Described as sustained release tacrolimus formulations. This also mentions being granted as U.S. Pat. No. 6,440,458, U.S. Pat. No. 6,576,259, and U.S. Pat. No. 6,884,433.
WO 2005/020993 (by the present inventors): Discusses different tacrolimus formulations tested in Beagle dogs and minipigs, showing improved bioavailability.
WO 2005/020994 (by the same inventors): Relates to solid dispersions comprising tacrolimus.
WO 03/004001: Describes a method for preparing particulate material by controlled agglomeration.
WO 00/50007 (Lipocine, Inc.): Discloses amphiphillic surfactants.

Analysis of Prior Art and Potential Anticipation under 35 U.S.C. § 102:

Anticipation under 35 U.S.C. § 102 requires that a single prior art reference discloses every element of a claimed invention, either expressly or inherently.

Here's an analysis of the identified prior art documents:

EP-A-0 184 162
- Full Citation: EP-A-0 184 162
- Publication/Filing Date: Not explicitly stated in the provided text, but it predates the priority date of US8664239 (2007-05-30) as it describes the preparation of tacrolimus.
- Brief Description: Describes the preparation of tacrolimus.
- Potential Anticipation: This reference likely anticipates the mere compound "tacrolimus" itself. However, US8664239 claims extended release oral dosage forms of tacrolimus with specific dissolution profiles and pharmacokinetic properties, as well as methods of treatment and conversion using such forms. Therefore, EP-A-0 184 162, while fundamental to the existence of tacrolimus, would not anticipate the novel formulation or method claims of US8664239, as it does not disclose all elements of those claims.
EP-A-0 444 659
- Full Citation: EP-A-0 444 659
- Publication/Filing Date: Not explicitly stated, but predates US8664239.
- Brief Description: Discloses analogues of tacrolimus.
- Potential Anticipation: Similar to EP-A-0 184 162, this reference would anticipate the existence of certain tacrolimus analogues but would not anticipate the specific extended release formulations or methods claimed in US8664239.
U.S. Pat. No. 6,387,918
- Full Citation: U.S. Pat. No. 6,387,918
- Publication/Filing Date: Not explicitly stated, but predates US8664239.
- Brief Description: Discloses analogues of tacrolimus.
- Potential Anticipation: Like the above, this patent would anticipate the existence of certain tacrolimus analogues but not the specific extended release formulations or methods claimed in US8664239.
WO99/49863 (Fujisawa Pharmaceutical Co.)
- Full Citation: WO99/49863, also granted as U.S. Pat. No. 6,440,458, U.S. Pat. No. 6,576,259, and U.S. Pat. No. 6,884,433.
- Publication/Filing Date: Not explicitly stated for WO99/49863, but the "Prior art keywords" for US8664239 list a "Prior art date" of 2007-05-30. Given the "WO99" in the publication number, its filing/publication would be in 1999.
- Brief Description: Describes sustained release tacrolimus formulations with a T63.2% value between 0.7 and 15 hours. The most preferred embodiment has a T63.6 value of 2-5 hours. Example formulations have T63.6% values from 1.9 to 8.2 hours.
- Potential Anticipation: This is a highly relevant reference as it specifically deals with sustained-release tacrolimus formulations.
  - Claim 1 of US8664239 requires a release of at most 63.5% of the active substance at the 12-hour time point under specified dissolution conditions. WO99/49863 describes formulations where the time for dissolving 63.2% (T63.2% value) is between 0.7 and 15 hours. While some formulations in WO99/49863 could fall within the "at most 63.5% at 12 hours" (e.g., a formulation that releases 63.2% at 15 hours would also release less than 63.5% at 12 hours), the stated "most preferred embodiment" has a T63.6 value of 2-5 hours, and example formulations range from 1.9 to 8.2 hours. These faster release profiles likely do not meet the "at most 63.5% at 12 hours" limitation of Claim 1. However, a detailed comparison of the specific dissolution curves and conditions would be required to definitively determine anticipation. The patent text of US8664239 itself distinguishes its "very extended period of time" release from WO99/49863, stating that a formulation with 63.2% released in 42 minutes "seems to be only marginally different from the conventional immediate release formulation of tacrolimus." This suggests that the invention believes its release profile is significantly slower than those generally preferred or exemplified in WO99/49863.
  - Claim 11 of US8664239 specifies pharmacokinetic parameters (Cmax at most 15 ng/mL and AUC(0-96 h) at least 45 ng·h/L for a 5mg dose in fasted healthy subjects). WO99/49863 discusses "improved bioavailability" but does not explicitly provide these specific Cmax and AUC values, making direct anticipation of Claim 11 less likely without further detailed analysis of the in vivo data in WO99/49863.
  - Claim 18 of US8664239 relates to a conversion method with a specific dose reduction. While WO99/49863 describes sustained release, it does not explicitly disclose this specific conversion ratio or method.
WO 2005/020993 (by the present inventors)
- Full Citation: WO 2005/020993
- Publication/Filing Date: Not explicitly stated, but "WO 2005" indicates a publication year of 2005, predating the priority date of US8664239.
- Brief Description: Tested different tacrolimus formulations (fast and slow release) in Beagle dogs and minipigs, demonstrating improved bioavailability compared to Prograf®. This indicates improved bioavailability could be linked to tacrolimus being in a dissolved state.
- Potential Anticipation: This reference, by the same inventors, focuses on improved bioavailability. While it generally discusses improved bioavailability for tacrolimus, it does not necessarily disclose the specific extended release profile of Claim 1 or the precise pharmacokinetic parameters of Claim 11. It also doesn't specify the conversion method of Claim 18. It serves as background art highlighting the challenge and general direction of research.
WO 2005/020994 (by the same inventors)
- Full Citation: WO 2005/020994
- Publication/Filing Date: Not explicitly stated, but "WO 2005" indicates a publication year of 2005, predating the priority date of US8664239.
- Brief Description: Relates to solid dispersions comprising tacrolimus.
- Potential Anticipation: This reference relates to the formulation type (solid dispersions) that could be used in an extended release product. However, it does not, by itself, disclose the specific release profile, pharmacokinetic parameters, or conversion methods claimed in US8664239. The invention states that solid dispersions "will contribute to a predictable and constant in vivo release of tacrolimus" and that "at least a part of tacrolimus ... is present in the composition in the form of a solid solution including a molecular dispersion and a solid dispersion." This suggests WO 2005/020994 teaches a component or a way of formulating that is used in US8664239, rather than anticipating the entire claimed invention.
WO 03/004001
- Full Citation: WO 03/004001
- Publication/Filing Date: "WO 03" indicates a publication year of 2003, predating the priority date of US8664239.
- Brief Description: Describes a process for the preparation of particulate material by a controlled agglomeration method, involving spraying a melted first composition onto a second solid carrier medium. This method is described as "particularly useful" for preparing the pharmaceutical compositions of US8664239.
- Potential Anticipation: This reference anticipates the method of preparing particulate material, which may be a component of the claimed dosage form. However, it does not anticipate the specific extended release profile, pharmacokinetic parameters, or treatment methods of US8664239. It teaches a process for making a component, not the final product with all its claimed characteristics.
WO 00/50007 (Lipocine, Inc.)
- Full Citation: WO 00/50007 in the name of Lipocine, Inc.
- Publication/Filing Date: "WO 00" indicates a publication year of 2000, predating the priority date of US8664239.
- Brief Description: Discloses amphiphilic surfactants suitable for use in compositions.
- Potential Anticipation: This reference anticipates the use of certain excipients (surfactants) that may be included in the dosage forms of US8664239. It does not anticipate the overall extended release formulation, its performance characteristics, or the methods of treatment.

Conclusion on Most Relevant Prior Art:

Based on the descriptions, WO99/49863 (Fujisawa Pharmaceutical Co.) appears to be the most relevant prior art. It specifically addresses sustained-release tacrolimus formulations, which is the core subject of US8664239. While US8664239 aims to distinguish itself by a more extended release profile and improved pharmacokinetic performance, WO99/49863's disclosure of sustained-release tacrolimus and its dissolution characteristics would be the closest reference for anticipation of the formulation claims, particularly Claim 1. A thorough comparison of the dissolution methodologies and results would be critical to determine if any specific embodiment within WO99/49863 explicitly or inherently meets the "at most 63.5% at 12 hours" criterion of Claim 1.

The other references (EP-A-0 184 162, EP-A-0 444 659, U.S. Pat. No. 6,387,918, WO 2005/020993, WO 2005/020994, WO 03/004001, WO 00/50007) provide background on tacrolimus, its analogues, formulation components, or general manufacturing methods, but do not appear to disclose the full scope of the specific extended release dosage form, its in vivo characteristics, or the particular conversion methods claimed in US8664239.