More than the mere look of a compound is required to establish obviousness
| January 22, 2019
Amerigen Pharmaceuticals v. UCB Pharma GMBH
January 11, 2019
Before Lourie, Chen and Stoll. Opinion by Lourie.
Summary
Amerigen appeals an inter parties review Decision by the U.S. Patent and trademark Office Patent Trial and Appeal Board (hereinafter “the Board”) that the U.S. Patent No. 6,858,650 (hereinafter ‘650) was not unpatentable as obviousness. The CAFC held that there was substantial evidence to support the Board’s findings. The CAFC affirmed the Board’s findings.
Details
The U.S. Patent No. 6,858,650 (hereinafter ‘650) claims some chemical derivative of 3,3‑diphenylpropylamines, including fesoterodine. Fesoterodine, an antimuscarinic drug with the following chemical structure:
“Fesoterodine is a prodrug of the active compound 5-hydroxymethyl tolterodine (hereinafter “5‑HMT”). A prodrug is an inactive molecule that, once inside the body, transforms to an active therapeutic agent.
5‑HMT is a metabolite of the compound tolterodine, an older antimusarinic drug….” Id. at 3. 5-HMT is an active metabolite, which has its own antimuscaranic activity and can contribute to the therapeutic effect of tolterodine. Tolterodine is converted to 5-HMT, once ingested by a patient, by cytochrome P450 2D6 (hereinafter “CYP2D6”). CYP2D6 converts the methyl group at the 5-position of the benzene ring of tolterodine to a hydroxylmethyl group in 5‑HMT. The following is the chemical structures of tolterodine and 5-HMT.
A noted distinction between 5-HMT and fesoterodine is present at the 2-position of the benzene ring. In fesoterodine, an isobutyryl ester is at the 2-position. In 5-HMT, the 2-postion is a hydroxyl group.
An inter partes review (IPR) of ‘650 was brought by Mylan Pharmaceuticals Inc. The Board instituted the review based on “(1)obviousness over the Detrol Label, Postlind, Bundgaard, Bundgaard PCT, and Berge; and (2) obviousness over Brynne, Bundgaard, Bundgaard PCT, and Johansson.” Id. at 4. After the institution of the IPR, Amerigen joined as a party to the proceeding.
In the IPR, Petitioners argued that there was sufficient motivation for a skilled artisan to modify 5-HMT. Petitioners’ Expert testified that 5-HMT had insufficient lipophilicity and this would cause bioavailability problems. Id. at 7. The Expert, citing Brynne as support, stated that tolerodine is 10-fold more lipophilic than 5-HMT. UCB argued that there was no basis to allege modification of 5-HMT due to a bioavailability issue. UCB argued that none of the cited art suggested an issue regarding absorption by 5-HMT and further argued that “the lipophilicity of 5-HMT relative to tolterodine…did not show that 5-HMT had a bioavailability problem.” Id. at 7. Further, UCB’s Expert testified to an analysis of 5‑HMT using the Rule of 5 by Lipinski, which assesses 4 inherent properties of a compound to predict a potential bioavailability problem, and found that none of properties indicated a bioavailability problem for 5-HMT. Id. at 7. Petitioner’s Expert agreed that a skilled artisan would use the Rule of 5 to determine if there a potential bioavailability problem.
The Board held that, while a skilled artisan would have reason to choose 5-HMT as a lead compound, said artisan would not have been motivated to modify 5-HMT to achieve a prodrug wherein the 2-position hydroxyl group is replaced with an alkyl ester of six or fewer carbons. Id. at 6 and 7. Moreover, the Board, crediting UCB’s Expert, held that a skilled artisan would not have been motivated to modify 5‑HMT due to a bioavailability issue. Further, the Board, found that:
- Since there is no bioavailability issue, a skilled artisan would not have any reason or motivation to achieve a 5-HMT prodrug;
- Designing a prodrug is difficult since a skilled artisan must consider toxicity, bioavailability, and other drug characteristics of two compounds, rather than just one;
- Petitioners failed to establish that an ester of 5-HMT would be inactive, an essential characteristic of a prodrug; and
- Petitioners did not present any prodrugs in the same chemical class, with the same mechanism of action or the in the same field of treatment.
Id. at 8. The Board concluded that it would not have been obvious to develop a prodrug of 5‑HMT. Furthermore, the Board held that achieving the compounds claimed in the ‘650 patent would not have been a matter of routine optimization; none of the cited art disclosed the molecule fesoterodine and that there were too many possibilities of molecular modifications of 5-HMT consistent with a prodrug design to render obvious the compounds claimed in the ‘650 patent. The Board, relying upon UCB’s Expert, held that a skilled artisan may consider esterifying the hydroxy groups at the 2-position and the 5-postion, but that even if said artisan only considered esterification of the 2-position hydroxy, there was not reason or motivation to achieve an ester of six carbons or less and further, even if all possible esters were limited to only alkyl esters of 6 carbons or less at the 2-position, there would still be 86 possibilities disclosed. The Board held it would not be routine to test each of the 86 possibilities. Id. at 9.
Amerigen appealed the holding of the Board and argued before the CAFC that the Board’s holding was improper because:
- The Board did not understand the argument regarding lipophilicity and that a skilled artisan would have motivation to increase lipophilicity of 5-HMT for its own sake (motivation)
- An excessive burden was place upon Petitioner to establish a motivation to make 5-HMT a prodrug (burden)
- The Board did not give sufficient consideration to their routine optimization argument (routine optimization)
Id. at 16 and 17. Further, Amerigen argued that the Board did not give sufficient consideration to their argument regarding the effect of a patent claiming 5-HMT. UCB argued that Amerigen did not present a legal error committed by the Board and that the Board’s findings were supported by substantial evidence. (Side Note – UCB also argued that Amerigen lacked standing to bring an appeal. The CAFC held that Amerigen had standing. This issue is not addressed herein).
The CAFC affirmed the Board’s decision, finding that there was sufficient evidence to support their factual findings. “A finding is supported by substantial evidence if a reasonable mind might accept the evidence as adequate to support the finding. Consol. Edison Co. v. NLRB, 305 U.S. 197, 229 (1938).” Id. at 17.
Regarding Amerigen’s first argument (motivation), the CAFC concluded that there was substantial evidence to support the Board’s holding that there is no reason or motivation to modify 5-HMT to increase lipophilicity. The CAFC noted the Board’s holding that UCB’s Expert “better addressed the bioavailability issue and that lipophilicity of 5-HMT relative to tolterodine did not demonstrate a bioavailability problem. We agree with UCB that a reasonable fact finder could have weighted Dr. Roush’s (UCB Expert) testimony over Dr. Patterson’s (Petitioner’s Exert).” Id. at 19. The CAFC also noted the Rule of 5 assessment of 5-HMT by UCB’s Expert that found that there was “no reason to suspect that 5-HMT would possess poor oral absorption.” Id. at 19.
Before the CAFC, Amerigen argued that “there need not be a specific problem with bioavailability of 5-HMT for one of ordinary skill in the art to be motivated to modify 5-HMT to further improve its bioavailability.” Id. at 19. The CAFC determined that this was merely a conclusory argument that was insufficient to overcome the substantial evidence that supported the Board’s holding.
Regarding Amerigen’s second argument (burden), the CAFC held that the Board correctly found that Petitioners did not meet their burden of proof (“In an IPR, the petitioner has the burden of proving unpatentability by a preponderance of the evidence. 35 U.S.C. § 316(e).” Id. at 18.) Relying upon Bundgaard, the Board noted that a prodrug is an inactive drug. The Board also noted that Petitioners failed to present any evidence that an ester of 5-HMT would be inactive. The CAFC held that the “Board sensibly found that a skilled artisan would ‘seek some degree of certainty that a prodrug of a particular molecule would be inactive before embarking on the process of attempting to create the prodrug’ and the petitioners failed to provide any such certainty.” Id. at 21.
Before the CAFC, Amerigen argued that the Board impermissible placed too high of a burden on Petitioners by requiring them to present a prodrug that was analogous to 5-HMT. The Board had noted that Petitioners did not present any evidence of a prodrug that would be analogous to 5-HMT. The CAFC held that the Board did not commit an error. The Board did not require such evidence but merely found the lack of such evidence to further support UCB’s position. The CAFC held that the Board inquiring as to the existence or not of a prodrug, similar to the claimed compounds, is not a dispositive error.
Regarding Amerigen’s third argument (routine optimization), the CAFC held that there was sufficient substantial evidence to support the Board’s holding that the cited art did not render obvious achieving the claimed monoester substitution solely at the 2-position of a 5-HMT and that Amerigen did not establish a discernible error in the Board’s analysis.
The Board had found 1) in view of Bundgaard, a skilled artisan would consider diester substitutions as well as other prodrug moieties, 2) a skilled artisan would consider modifying the 5-position and/or the 2‑position, and 3) Bundgaard did not disclose isobutyryl ester of fesoterodine. The Board held it would not have been routine for a skilled artisan to achieve the claimed molecular modification to 5-HMT to achieve the claimed compounds of the ‘650 patent. Before the CAFC, Amerigen argued that “Bundgaard disclosed esters as prototypical prodrug moieties and that modifying the 2-position alone would have been the most obvious choice.” Id. at 22. The CAFC noted that the Board considered the disclosure of ester prodrugs by Bundgaard but also considered the disclosure by Bundgaard of many other prodrug substitutions. UCB’s Expert testified to at least 6 categories of additional substitutions. The Board held that modifications at the 5-position was as likely as modifications at the 2-position since the cited art “did not indicate a preference for either the 2- or 5-position, and the inventors themselves considered modifying the 5-position.” Id. at 22. The Board dismissed as unpersuasive testimony by Petitioner’s Expert that modifying only the 5-position would pose a risk of transesterification since the risk was not sufficiently explained.
Lastly, before the CAFC, Amerigen argued that the Board did not give sufficient weight to the Petitioner’s argument, presented in a single-sentence footnote in the petition, that a skilled artisan would have been motivated to modify 5-HMT because 5-HMT was patented at the time of invention. The CAFC held that even if a patent of 5-HMT provided a commercial motivation to modify 5‑HMT, such a motivation did not render the claimed compounds of the ‘650 patent obvious. The CAFC held that Amerigen did not meet its burden that “the ‘prior art would have suggested making the specific molecular modifications necessary to achieve the claimed invention.” Takeda Chem. Indus., Ltd. v. Alapharm Pty., Ltd., 492 F.3d 1350, 1356 (Fed. Cir. 2007) (emphasis added) (quoting In re Deuel, 51 F.3d 1552, 1558 (Fed. Cir. 1995)). A general motivation to modify 5-HMT based on a prior patent would not suffice….” Id. at 23.
The CAFC, affirming the holding of the Board, stated that “[A]ny compound may look obvious once someone has made it and found it to be useful, but working backwards from that compound, with the benefit of hindsight, once one is aware of it does not render it obvious.” Id. at 23.
Take away
- Ensure that there is a clearly identified reason for making the proposed modification. General assertions for making a proposed modification may not establish a prima facie case of obviousness
a. Ensure that the clearly identified reason is logical. Furthermore, ensure the alleged reason has a correlation to the cited feature.
2. Consider the breadth of the possibilities for a substitution presented in the cited art. The disclosure regarding a specific substitution may be exponentially greater when one considers more than one reference and/or more than one possible location of said substitution, e. 2‑position and/or 5-position of a benzene ring.
BEWARE OF A SURPRISE CO-OWNER OF A PATENT WHO DOES NOT WANT TO ENFORCE ITS PATENT
| June 12, 2014
STC.UNM v. Intel Corp.
June 6, 2014
Panel: Rader, Dyk, and Newman. Opinion by Rader. Dissent by Newman
Summary:
The ‘998 patent was a CIP of the ‘312 patent, which was jointly owned by STC.UNM and Sandia. Because a terminal disclaimer (which required a common ownership of both patents) was filed during prosecution of the ‘998 patent, STC.UNM and Sandia are co-owners of the ‘998 patent even if Sandia did not make any contribution to the ‘998 patent. STC.UNM filed an infringement suit concerning the ‘998 patent against Intel, and Sandia refused to join the lawsuit. The district court dismissed the case for a lack of standing, and the CAFC affirmed by holding that all co-owners must ordinarily consent to join as plaintiffs in an infringement suit. Furthermore, both the district court and the CAFC refused to involuntarily join Sandia to the case as a necessary party (FRCP Rule 19).
본사건은연방지방법원뉴멕시코지원의판결에불복하여 STC/UNM이연방순회항소법원 (CAFC)에항소한사건이다. CAFC는연방지방법원과같이‘312 특허를바탕으로일부계속출원된특허 (continuation-in-part)인‘998 특허심사도중원고STC/UNM가존속기간포기서 (terminal disclaimer)를제출함으로써특허심사거절을극복하였으므로, STC/UNM과 Sandia는‘998 특허의공동소유자(co-owners)라고판단하였다 (Sandia는‘998 특허발명에공헌을하지않았다). 또한CAFC는 Sandia의소송참여의사에상관없이 STC/UNM이인텔을상대로‘998 특허침해소송을제기한것에대해STC/UNM은원고적격(standing)이없다고판단하여소송을기각하였다. 왜냐하면특허침해소송에서는특허의모든공동소유자가원고로참여해야하지만Sandia는소송참여를하지않기로결정하였기때문이다. 마지막으로CAFC는연방지방법원과마찬가지로본사건은연방민사소송규칙 19조의involuntary joinder rule이적용되지않아Sandia를원고로강제참여시킬수없다고판단하였다.
Tags: Continuation-in-part-application > Joinder > Rule 19 > Standing > terminal disclaimer
License agreement to a patent may extend to a corresponding reissue patent
| December 19, 2012
Intel Corp. v. Negotiated Data Solutions, Inc.
December 17, 2012
Panel: Prost, Wallach and Linn. Opinion by Linn.
Summary
Intel and National Semiconductor Corp. (“National”) entered into a cross-licensing agreement. The agreement gave Intel rights to National’s patents and patent applications having an effective filing date during the period in the agreement which lasted from 1976 to 2003. This case deals with four patents that were covered under the agreement. National assigned these patents to Vertical Networks, Inc. (“Vertical”) in 1998. Vertical then filed broadening reissue applications for three of the patents. In 2003, Vertical assigned the original patents and the reissue applications to Negotiated Data Solutions, Inc. (“N-Data”). In 2005 and 2006, well after the agreement expired, the PTO issued reissue patents to N-Data. The issue in this case is whether the agreement, which licenses National patents to Intel, automatically extends to any reissue patents that are derived from those licensed National patents. The CAFC held that the license agreement extends to the full scope of any coverage available by way of reissue for the invention disclosed.
Tags: assignment > continuation > licensing > reissue
A Federal Circuit Lesson on the Structuring of Employment Agreements to Ensure That a Company Owns Its Employees’ Inventions
| July 25, 2012
Preston v. Marathon Oil Company and Thomas Smith
July 10, 2012
Panel: Bryson, Dyk and O’Malley. Opinion by O’Malley.
Summary
In this case, an employee, Yale Preston (“Preston”), executed an employment agreement about one month after starting to work as an employee for Marathon Oil Company (“Marathon”). Whether or not the execution of an agreement after starting employment requires further consideration beyond “continued employment” varies based on state law. Here, the Federal Circuit held that no further consideration was required under Wyoming state law and that the employer, Marathon, owned the invention at issue by virtue of the employment agreement. The Federal Circuit further held that Preston did not breach the employment agreement by failing to later sign a subsequent assignment because the employment agreement included the language “does hereby assign” in relation to future inventions, whereby the invention at issue was assigned to Marathon by the employment agreement regardless of whether the invention was after the execution of the employment agreement.
Tags: assignment > contract > employee > employment contract > ownership
