Louie Daniel. Garcia et al.

Patent Trials and Appeals BoardSep 16, 2019

13283450 - (D) (P.T.A.B. Sep. 16, 2019)

UNITED STATES PATENT AND TRADEMARK OFFICE UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O. Box 1450 Alexandria, Virginia 22313-1450 www.uspto.gov APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 13/283,450 10/27/2011 Louie Daniel Garcia PCIRA.037A 8217 20995 7590 09/16/2019 KNOBBE MARTENS OLSON & BEAR LLP 2040 MAIN STREET FOURTEENTH FLOOR IRVINE, CA 92614 EXAMINER KISHORE, GOLLAMUDI S ART UNIT PAPER NUMBER 1612 NOTIFICATION DATE DELIVERY MODE 09/16/2019 ELECTRONIC Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address(es): efiling@knobbe.com jayna.cartee@knobbe.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE PATENT TRIAL AND APPEAL BOARD __________ Ex parte LOUIE DANIEL GARCIA, LIANGJIN ZHU, WILLIAM JOSEPH LAMBERT, and GARY PATOU __________ Appeal 2018-007990 Application 13/283,4501 Technology Center 1600 __________ Before DONALD E. ADAMS, JOHN G. NEW, and RACHEL H. TOWNSEND, Administrative Patent Judges. TOWNSEND, Administrative Patent Judge. DECISION ON APPEAL This is an Appeal under 35 U.S.C. § 134 involving claims to a formulation of one or more non-steroidal anti-inflammatory drugs, which have been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We reverse. 1 We use the word “Appellant” to refer to “Applicant” as defined in 37 C.F.R. § 1.42. Appellant identifies the real party in interest as Pacira Pharmaceuticals, Inc. (Appeal Br. 3.) Appeal 2018-007990 Application 13/283,450 2 STATEMENT OF THE CASE Non-steroidal anti-inflammatory drugs (NSAIDs) are administered both orally and intravenously. (Spec. ¶ 3.) “Oral NSAID treatment, however, has been linked to a variety of serious gastrointestinal complications, including peptic ulcer, digestive perforation, hemorrhage, colonic ulcer, and colitis.” (Id.) “GI toxicity is attributable to the magnitude and duration of drug exposure both in the GI tract following oral dosing and with high systemic levels of drug required to achieve efficacious drug levels at the synovial site of action[2].” (Id. ¶ 4.) Appellant’s invention is directed at a formulation of the NSAIDs meloxicam and/or piroxicam encapsulated in a multivesicular liposome3 which minimize the side effects of NSAIDs while maintaining or improving efficacy. (See id. ¶¶ 8, 28, claim 1) Claims 1, 62, 64, 68, 70, 71, 73, 74, 111, 112, 115–122, and 136 are on appeal. Claim 1 is representative and reads as follows: 1. A formulation of one or more non-steroidal anti- inflammatory drugs, comprising: one or more non-steroidal anti-inflammatory drugs selected from the group consisting of meloxicam and piroxicam; and multivesicular liposomes, wherein the multivesicular liposomes comprise a first aqueous phase and a second aqueous phase; 2 “[D]rugs are typically cleared in a matter of hours from the synovial fluid.” (Id. ¶ 5.) 3 “Topologically, multivesicular liposomes [“MVLs”] are defined as having multiple non-concentric chambers within each particle, resembling a ‘foam- like’ matrix; whereas multilamellar vesicles contain multiple concentric chambers within each liposome particle, resembling the ‘layers of an onion.’” (Id. ¶ 35.) Appeal 2018-007990 Application 13/283,450 3 wherein the one or more non-steroidal anti-inflammatory drugs are encapsulated in the first aqueous phase of the multi vesicular liposomes; and wherein the first aqueous phase comprises at least one pH modifier, said pH modifier comprises an organic acid or an organic base, or a combination thereof. (Appeal Br. 17.) The following grounds of rejection by the Examiner are before us on review: Claims 1, 62, 64, 68, 70, 71, 73, 74, 111, 112, 115–122, and 136 under 35 U.S.C. § 103 as unpatentable over Weiner4 or McLean,5 Sankaram,6 and Gruber.7 Claims 1, 62, 64, 68, 70, 71, 73, 74, 111, 112, and 115–1228 under 35 U.S.C. § 103 as unpatentable over Weiner or McLean, Kim ’573,9 and Gruber. 4 Weiner et al., US 6,759,057 B1, issued July 6, 2004. 5 McLean et al., US 2003/0235610 A1, published Dec. 25, 2003. 6 Sankaram et al., US 6,132,766, issued Oct. 17, 2000. 7 Gruber et al., US 2010/0035937 A1, published Feb. 11, 2010. 8 Additional claims were rejected by the Examiner in the Office Action from which the appeal was taken, but those claims had been canceled prior to issuance of that Office Action, and thus, are no longer pending in the Application on Appeal. (See Amendment and Response to Office Action dated April 20, 2017 (cancelling claims 20, 65–67, 69, 87, 89–91, 93–97, 99–102, 107, 108, 110, 123–125, and 128–135).) 9 Kim, U.S. Patent No. 5,759,573, issued June 2, 1998. Appeal 2018-007990 Application 13/283,450 4 Claims 1, 62, 64, 68, 70, 71, 73, 74, 111, 112, 115–122, and 136 under 35 U.S.C. § 103 as unpatentable over Hofland,10 Cipolla11, Kim ’147,12 and Gruber. DISCUSSION Weiner, McLean, Sankaram, and Gruber The Examiner finds that Weiner and McLean both teach liposomal formulations that contain a non-steroidal anti-inflammatory drug (NSAID), where piroxicam is identified as one such NSAID. (Final Action 2.) The Examiner recognizes that neither reference teaches encapsulation of the NSAID in a MVL. (Id.) The Examiner finds, however, that Sankaram teaches a variety of drugs encapsulated in MVLs. (Id. at 3.) The Examiner finds that Sankaram indicates that the internal membranes of the MVL “serve to cover increased mechanical strength to the vesicle, while still maintaining a high volume lipid ratio compared to multi-lamellar vesicles.” (Id. (citing Sankaram 2:28– 39).) According to the Examiner, it would have been obvious to one of ordinary skill in the art “to encapsulate NSAIDS of Weiner or McLean in the [MVL] and treat inflammation since Sankaram teaches the advantages of [MVL]” and/or because “Sankaram teaches that any drug can be encapsulated within the [MVL] and NSAIDS are known to be encapsulated within liposomes as evident from Weiner and McLean.” (Id.) 10 Hofland et al., US 2004/0224010 A1, published Nov. 11, 2004. 11 Cipolla et al., US 2012/0244206 A1, published Sept. 27, 2012. 12 Kim et al., US 5,723,147, issued Mar. 3, 1998. Appeal 2018-007990 Application 13/283,450 5 Regarding encapsulation of NSAIDs in an aqueous phase of the MVL rather than in the lipid layers of the liposomes of Weiner and McLean, the Examiner notes that Gruber teaches NSAIDs, such as naproxen and diclofenac which are water insoluble hydrophobic compounds, “can be converted into salt form to obtain soluble forms.” (Id. at 3–4.) According to the Examiner, it would have been obvious to make the NSAID into a salt form “since such [a] procedure makes the NSAID soluble as taught by Gruber” (id. at 3), and then encapsulate the NSAID in the aqueous compartment of the MVL “instead of sequestering them into [the] lipid bilayer of the liposomes” (id. at 4). We disagree with the Examiner’s conclusion of obviousness. As Appellant points out, Gruber teaches a solubilized NSAID salt where the NSAID contains “at least one carboxylic group.” (Gruber ¶ 25; Appeal Br. 13 (citing Declaration of Kathleen Los13 ¶ 7).) The Examiner did not address this argument directly. (Ans. 3–5.) Instead, the Examiner argued that generally increasing the pH to dissolve NSAIDs “is suggested by Gruber [and] determining the solubility conditions of any compound is within the skill of the art of [the] highly developed field of chemistry.” (Id. at 6.) We disagree that one of ordinary skill in the art would have had a reasonable expectation of success in solubilizing meloxicam or piroxicam by making a salt form using the method described by Gruber. Gruber notes that “[a] common disadvantage of this group of drugs[, i.e., NSAIDs,] is their poor solubility.” (Gruber ¶ 2.) Yet Gruber only discloses making water- 13 The Los Declaration is dated April 19, 2017. Appeal 2018-007990 Application 13/283,450 6 soluble salt forms of NSAIDs that contain at least one carboxylic group. (Gruber ¶¶ 24–25.) We determine that one of ordinary skill in the art would have reasonably concluded from this disclosure that not all NSAIDs may be provided as a water-soluble salt form, and thus, we disagree with the Examiner that increasing the pH to dissolve any NSAID is suggested by Gruber (Ans. 6). As Ms. Los attests (Los Declaration ¶ 7), and the Examiner does not dispute, neither meloxicam nor piroxicam have a carboxylic group. Thus, we agree with Appellant (Reply Br. 7), that in light of Gruber’s narrow disclosure of the NSAIDs that could be made into solubilized salts as NSAIDS having a carboxylic group, one of ordinary skill in the art would not have had a reasonable expectation of success in achieving a soluble salt form of meloxicam or piroxicam by simply solubilizing those compounds “at an alkaline pH as taught by Gruber” (Final Action 5). Consequently, we reverse the Examiner’s rejection of the claims as being obvious over Weiner, McLean, Sankaram, and Gruber. Weiner, McLean, Kim, and Gruber The Examiner’s rejection under this ground relies on Gruber for the same principle as discussed above. (See Final Action 6.) For the reasons just discussed, we disagree that one of ordinary skill in the art would have had a reasonable expectation of success in solubilizing meloxicam or piroxicam by making a salt form as described by Gruber. Thus, we reverse the Examiner’s obviousness rejection under this ground. Appeal 2018-007990 Application 13/283,450 7 Hofland, Cipolla, Kim, and Gruber The Examiner’s rejection under this ground relies on Gruber for the same principle as discussed above. (See Final Action 7–8; Ans. 6.) For the reasons just discussed we disagree that one of ordinary skill in the art would have had a reasonable expectation of success in solubilizing meloxicam or piroxicam by making a salt form as described by Gruber. Thus, we reverse the Examiner’s obviousness rejection under this ground. SUMMARY In summary: Claims Rejected Basis Affirmed Reversed 1, 62, 64, 68, 70, 71, 73, 74, 111, 112, 115–122, and 136 § 103 over Weiner or McLean, Sankaram, and Gruber 1, 62, 64, 68, 70, 71, 73, 74, 111, 112, 115–122, and 136 1, 62, 64, 68, 70, 71, 73, 74, 111, 112, and 115–122 § 103 over Weiner or McLean, Kim ’573, and Gruber 1, 62, 64, 68, 70, 71, 73, 74, 111, 112, and 115–122 1, 62, 64, 68, 70, 71, 73, 74, 111, 112, 115–122, and 136 § 103 over Hofland, Cipolla, Kim ’147, and Gruber 1, 62, 64, 68, 70, 71, 73, 74, 111, 112, 115–122, and 136 Overall Outcome 1, 62, 64, 68, 70, 71, 73, 74, 111, 112, 115–122, and 136 REVERSED