Ex Parte Demmer et al

Patent Trial and Appeal BoardOct 31, 2012

10516405 (P.T.A.B. Oct. 31, 2012)

MOD PTOL-90A (Rev.06/08) APPLICATION NO./ CONTROL NO. FILING DATE FIRST NAMED INVENTOR / PATENT IN REEXAMINATION ATTORNEY DOCKET NO. 10/516,405 11/30/2004 Wolfgang Demmer et al. 3568.0103 EXAMINER CHERNOFF, VILHAUER, MCCLUNG & STENZEL, LLP Suite 1600 601 S.W. Second Avenue PORTLAND OR 97204-3157 FERNANDEZ, SUSAN EMILY ART UNIT PAPER NUMBER 1651 MAIL DATE DELIVERY MODE 10/31/2012 PAPER 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. UNITED STATES DEPARTMENT OF COMMERCE U.S. Patent and Trademark Office Address : COMMISSIONER FOR PATENTS P.O. Box 1450 Alexandria, Virginia 22313-1450 www.uspto.gov UNITED STATES PATENT AND TRADEMARK OFFICE _____________________________________________________________________________________ UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE PATENT TRIAL AND APPEAL BOARD __________ Ex parte WOLFGANG DEMMER, DIETMAR NUSSBAUMER, and HANS-HEINRICH HÖRL __________ Appeal 2011-0100301 Application 10/516,405 Technology Center 1600 __________ Before TONI R. SCHEINER, STEPHEN WALSH, and ERICA A. FRANKLIN, Administrative Patent Judges. SCHEINER, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 from the final rejection of claims 11, 14, and 15, directed to a device for removing proteases from biological fluids. The claims have been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We reverse. 1 This appeal is related to Appeal No. 2011-010437 (in Application No. 11/436,861). We have considered the two appeals together. Appeal 2011-010030 Application 10/516,405 2 STATEMENT OF THE CASE Claims 11, 14, and 15 are pending and on appeal. Claim 11 is representative of the subject matter on appeal: 11. A device for removing proteases from biological fluids and pharmaceutical solutions comprising a housing having a fluid inlet and a fluid outlet, said housing containing a plurality of membranes arranged therein in series, wherein said membranes each consist essentially of a microporous membrane containing epoxy groups chemically coupled to at least one protease inhibitor via said epoxy groups, wherein said at least one protease inhibitor is selected from the group consisting of pepstatin, bestatin, diprotin, antipain, chymostatin, leupeptin, E64, TLCK and p-aminobenzamidine. The Examiner relies on the following evidence: JERRY MARCH, ADVANCED ORGANIC CHEMISTRY 369 (3d ed. 1985). P. Langlotz & K.H. Kroner, Surface-modified membranes as a matrix for protein purification, 591 JOURNAL OF CHROMATOGRAPHY 107-113 (1992). GREG T. HERMANSON ET AL., IMMOBILIZED AFFINITY LIGAND TECHNIQUES 166-169, 172, 173, 317-319, 354-359 (1992). Graham Preece et al., Metalloproteinase-mediated Regulation of L-selectin Levels on Leucocytes, 20 JOURNAL OF BIOLOGICAL CHEMISTRY 11634-11640 (1996). Xianfang Zeng & Eli Ruckenstein, Trypsin Purification by p-Aminobenzamidine Immobilized on Macroporous Chitosan Membranes, 37 IND. ENG. CHEM. RES. 159-165 (1998). p-Aminobenzamidine, http://www.chemicalbook.com/ProductChemicalPropertiesCB8384368_EN. htm. (visited September 3, 2009). I. Claims 11, 14, and 15 stand rejected under 35 U.S.C. §103(a) as unpatentable over Hermanson, Zeng, Langlotz, and Preece (Ans. 8-12). II. Claim 11 stands rejected under 35 U.S.C. § 103(a) as unpatentable over Zeng and Langlotz (Ans. 5-8). Appeal 2011-010030 Application 10/516,405 3 PRINCIPLES OF LAW The Examiner’s rejections must be supported by a preponderance of the evidence. See, e.g., Ethicon, Inc. v. Quigg, 849 F.2d 1422, 1427 (Fed. Cir. 1988). A rejection based on section 103 clearly must rest on a factual basis . . . In making this evaluation, all facts must be considered. The Patent Office has the initial duty of supplying the factual basis for its rejection. . . . To the extent the Patent Office rulings are so supported, there is no basis for resolving doubts against their correctness. Likewise, we may not resolve doubts in favor of the Patent Office determination when there are deficiencies in the record as to the necessary factual bases supporting its legal conclusion of obviousness. In re Warner, 379 F.2d 1011, 1017 (CCPA 1967). FINDINGS OF FACT 1. Hermanson teaches that “[t]he ligand p-aminobenzamidine (p- AB [or PAB]) has been used extensively for the purification of urokinases, serine proteases, plasminogen activators, and other similar enzymes” (Hermanson 167). According to Hermanson, “[i]mmobilized p-AB is best prepared by using a spacer arm to extend the ligand some distance from the matrix [e.g., agarose gel]. This allows approaching enzymes to wrap around the protruding ligand, reaching binding sites that may be somewhat buried below the surface of the protein” (id.). 2. Zeng discloses an affinity membrane selective for trypsin (a protease) comprising p-aminobenzamidine (PAB), immobilized on a macroporous chitosan membrane (Zeng, Abstract). According to Zeng, “succinic anhydride was first coupled to the chitosan membrane to obtain succinic carboxyl groups as spacers” and “[t]he Appeal 2011-010030 Application 10/516,405 4 succinylated chitosan membranes were then coupled with PAB” (id. at 160, col. 1), as shown below: (id. at 160, col. 2). 3. Langlotz discloses the coupling conditions for an epoxy- activated membrane using protein A, immunoglobulin G, and soybean trypsin inhibitor as a model system (Langlotz 107, col. 2). The functional groups involved in immobilization are not discussed. DISCUSSION I. Claims 11, 14, and 15 stand rejected as unpatentable over Hermanson, Zeng, Langlotz, and Preece. The issue raised by this rejection is whether the Examiner has established that it would have been obvious for one of ordinary skill in the art to couple a protease inhibitor, e.g., p-aminobenzamidine to a membrane containing epoxy groups, via the epoxy groups, given the evidence of record. The Examiner finds that Hermanson teaches that “it is essential to completely remove undesirable proteases from biological solutions” for many studies (Ans. 8), and “[e]xamples of [column chromatography] affinity supports successfully used for this purpose include immobilized soybean trypsin inhibitor and immobilized p-aminobenzamidine (PAB)” (id. at 8-9). Similarly, the Examiner finds that Zeng discloses “a device for removing Appeal 2011-010030 Application 10/516,405 5 proteases from biological and pharmaceutical solutions comprising a housing . . . containing a plurality of membranes arranged therein in series, wherein said membranes have [p-aminobenzamidine] PAB . . . bound thereto” (id. at 6). The Examiner acknowledges that neither Hermanson nor Zeng discloses PAB immobilized on an epoxy-functionalized membrane (id. at 6, 9). However, the Examiner finds that Langlotz discloses coupling proteins, specifically, protein A, rabbit IgG, and soybean trypsin inhibitor, to epoxy- activated membranes by a simpler, less time-consuming procedure than the procedures used by Hermanson and Zeng (id. at 10). The Examiner concludes that it would have been obvious for one of ordinary skill in the art to “substitute[] the epoxy-activated membrane of Langlotz et al for the chitosan membrane taught by Zeng et al, and then to couple the PAB to the epoxy-activated membrane for use as the membranes within the device of Zeng et al.” (Ans. 7) because “fewer steps and less time would have been required in binding the protease inhibitor(s) to the membrane” (id. at 11). The Examiner further finds that “[t]here would have been reasonable expectation of success in immobilizing at least one of the protease inhibitors . . . since the epoxy-activated membrane of Langlotz et al. is shown to be suitable for binding molecules via an amine terminal group (such as is found on PAB)” (id.). Appellants contend that nothing in the prior art suggests that Zeng’s PAB will bind an epoxy-activated membrane in a manner equivalent to the proteins immobilized by Langlotz (i.e., protein A, rabbit IgG, and soybean trypsin inhibitor) (App. Br. 4). More importantly, Appellants contend that both Hermanson and Zeng use spacers between PAB and the support matrix, Appeal 2011-010030 Application 10/516,405 6 and nothing in the evidence cited by the Examiner would have given one of ordinary skill in the art a reason to eliminate those spacers and bind the PAB directly to the epoxy-activated membrane. Appellants have the better position. Even if we were to accept the Examiner’s unsupported assertions that “the amine group of a protein reacts with the epoxy group of the epoxy-activated membrane” (Ans. 7), and that “PAB would react via [its] terminal amine group with the epoxy group of the epoxy-activated membrane in the same manner as proteins” (id. at 8), we are not persuaded that it would have been obvious for one of ordinary skill in the art to immobilize PAB on an epoxy-activated membrane. As discussed above, both Hermanson and Zeng use a spacer between PAB and the support matrix (FFs 1, 2), and Hermanson explains that “[t]his allows approaching enzymes [i.e., proteases to be removed from solution] to wrap around the protruding ligand, reaching binding sites that may be somewhat buried below the surface of the [protease]” (FF1). We see nothing in the evidence of record that would lead one of skill in the art to expect that the active site of PAB, which is much, much smaller than Langlotz’s proteins, would still be available to bind approaching proteases and remove them from solution, when bound directly to an epoxy-activated membrane. We find that the Examiner has not provided an adequate factual basis to establish that it would have been obvious for one of ordinary skill in the art to couple p-aminobenzamidine directly to an epoxy-activated membrane via the membrane’s epoxy groups. Accordingly, the rejection of the claims as unpatentable over Hermanson, Zeng, Langlotz, and Preece is reversed. Appeal 2011-010030 Application 10/516,405 7 II. Claim 11 stands rejected as unpatentable over Zeng and Langlotz. The issue raised by this rejection is the same as the previous rejection, and we find the evidence of record inadequate to support the rejection for the same reasons discussed above. The rejection of claim 11 as unpatentable over Zeng and Langlotz is reversed. SUMMARY I. The rejection of claims 11, 14, and 15 under 35 U.S.C. §103(a) as unpatentable over Hermanson, Zeng, Langlotz, and Preece is reversed. II. The rejection of claim 11 under 35 U.S.C. § 103(a) as unpatentable over Zeng and Langlotz is reversed. REVERSED cdc