Ex Parte Schilling et alDownload PDFPatent Trial and Appeal BoardMay 31, 201612016266 (P.T.A.B. May. 31, 2016) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE FIRST NAMED INVENTOR 12/016,266 01/18/2008 Stephan Schilling 26263 7590 05/31/2016 DENTONS US LLP P.O. BOX 061080 CHICAGO, IL 60606-1080 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 ATTORNEY DOCKET NO. CONFIRMATION NO. 2007 5610-0062 3954 EXAMINER WILSON, MICHAEL C ART UNIT PAPER NUMBER 1632 MAILDATE DELIVERY MODE 05/31/2016 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. PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte STEPHAN SCHILLING, HOLGER CYNIS, TORSTEN HOFFMANN, HANS-ULRICH DEMUTH, MICHAEL WERMANN, and KATRIN SCHULZ 1 Appeal2013-003190 Application 12/016,266 Technology Center 1600 Before LORA M. GREEN, JEFFREY N. FREDMAN, and ULRIKE W. JENKS, and, Administrative Patent Judges. JENKS, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to directed to a transgenic mouse overexpressing glutaminyl cyclase. The Examiner rejects the claims as containing new matter and obviousness. We have jurisdiction under 35 U.S.C. § 6(b ). We reverse. 1 According to Appellants, the Real Party in Interest is Probiodrug AG. (App. Br. 2.) Appeal2013-003190 Application 12/016,266 STATEMENT OF THE CASE Claims 1-3, 5-15, 17-24, 34, and 42-50 are on appeal2, and can be found in the Claims Appendix of the Appeal Brief. Claim 1 is representative of the claims on appeal, and reads as follows: 1. A transgenic mouse overexpressing glutaminyl cyclase (Qpct) whose genome comprises: a nucleic acid sequence encoding a mammalian glutaminyl cyclase (Qpct) operably linked to a promoter, wherein-said Qpct is overexpressed in said transgenic mouse as compared to a nontransgenic mouse. The Examiner rejects the claims as follows: I. claims 42, 43, 49, and 50 under 35 U.S.C. § 112, first paragraph as failing to comply with the written description requirement under 35 U.S.C. § 112, first paragraph as containing subject matter that was not described in the Specification as filed (Ans. 3---6); and II. claims 1-3, 5-15, 17-24, 34, and 42-50 under 35 U.S.C. § 103(a) as unpatentable over Yoshimura3 in view of GenBank Accession No: NM_Ol 7659 (human) or NM_027455 (mouse) (Ans. 6-7). I. Issue: New Matter The Examiner finds that some of the language recited in claims 42, 43, 49, and 50 is not supported by the as-filed Specification. (Ans. 3-5 and 10-13.) 2 Appellants note that claims 4, 16, 25-33, and 35--41 have been canceled (App. Br. 2). 3 Yoshimura et al., Overexpression of Type 7 Adenylyl Cyclase in the Mouse Brain Enhances Acute and Chronic Actions of Morphine, 58 Molecular Pharmacology 1011-1016 (2000). 2 Appeal2013-003190 Application 12/016,266 The issue is: Does the evidence of record support the Examiner's position that the Specification as filed does not provide sufficient support for the claimed "neurologically localized" or "brain localized" Qpct levels or activity in the transgenic mouse as claimed? Findings of Fact FF 1. The Specification provides "[ c ]omparison of QC-activity [ (glutaminyl cyclase-activity)] in the brain homogenates of transgenic mice expressing human QC neuron-specifically driven by the Thy- I [a neuron specific] promotor ... or murine QC ubiquitously (pbdl 7E3)." (Spec. 11: 24--27 .) "The terms 'QC' or 'Qpct' ... refer to the same and comprise glutaminyl cyclase (QC), i.e.glutaminyl- peptidecyclotransferase (EC 2.3.2.5.) and QC-like enzymes. QC and QC-like enzymes have identical or similar enzymatic activity, further defined as QC activity." (Spec. 25: 11-15.) FF2. The Specification provides "determination of QC-activity, 50 mg of brain tissue were homogenized in 1 ml of buffer consisting .... The hQC activity was determined applying a HPLC-assay." (Spec 70: 20- 33.) FF3. The Specification provides "[ q]uantitative real time R T-PCR using cDNA from brain, liver and kidney of QC transgenic (QC, N=2) mice and control (WT, N=2) mice as a template." (Spec 11:.) Principle of Law The Examiner "'bears the initial burden ... of presenting a prima facie case ofunpatentability.' In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992). "Insofar as the written description requirement is concerned, that 3 Appeal2013-003190 Application 12/016,266 burden is discharged by 'presenting evidence or reasons why persons skilled in the art would not recognize in the disclosure a description of the invention defined by the claims.' . . . If ... the specification contains a description of the claimed invention, albeit not in ipsis verb is (in the identical words), then the examiner ... , in order to meet the burden of proof, must provide reasons why one of ordinary skill in the art would not consider the description sufficient." In re Alton, 76 F.3d 1168, 1175 (Fed. Cir. 1996). Analysis With respect to claims 42 and 43, the Examiner finds that "determining neurologically localized levels of Qpct in the mouse" is not supported in the Application as filed. (See Ans. 3---6 and 10-11.) Similarly, with respect to claims 49 and 50, the Examiner finds that "determining brain localized levels of Qpct in the transgenic mouse" is also not supported in the Application as filed. (See Ans. 3---6 and 11-12.) Because the same issue is relevant to both rejections, we will discuss them together. Appellants contend that the Specification provides support for "transgenic mouse overexpressing Qpct driven by a neuron-specific promoter and detection of Qpct produced therefrom in neurological tissue." (App. Br. 20.) Appellants direct us to the disclosure in the Specification that describes assaying brain homogenate for QC activity in tissues, specifically, brain homogenates (App. Br. 20-26; see FFl & FF2). We note that the Specification also describes assaying for the transcription levels of QC using quantitative PCR in various tissues, such as brain, liver and kidney tissues (FF3). The Specification also compares the expression levels of QC from these different tissues (see Spec. Fig. lOA-D.). One of ordinary skill in the 4 Appeal2013-003190 Application 12/016,266 art would understand that brain tissue contains neurons - although we understand that a brain homogenate would not necessarily distinguish between different brain structures containing different neurons within the brain the claims do not require such differentiation. The Examiner has not directed us to any persuasive evidence that would indicate that the use of the term "localized" means anything other than pertaining to the neurons or the brain. We understand that in light of the Specification, "neurologically localized" or "brain localized" would be understood by the ordinary artisan to be directed to brain tissue as opposed to other body tissues. We conclude that the preponderance of the evidence of record does not support the Examiner's conclusion that the Specification fails to provide a description for the limitations of "neurologically localized" or "brain localized" levels of Qpct as recited in the claims. Accordingly, we reverse the rejection 42, 43, 49, and 50 as not complying with the written description requirement. II. Issue: Obviousness over Yoshimura and GenBank Sequences The Examiner finds that Yoshimura teaches the production of transgenic mice by adding a genome to the mice that "encod[ s] a cyclase gene operably linked to a brain specific promoter." (Ans. 6.) The Examiner acknowledges that "Yoshimura did not teach the cyclase was glutaminyl cyclase (Qpct)." (Id.) The Examiner explains that "Qpct is a member of the family of aminoacyltransferases (Wikipedia description of glutaminyl- peptide cyclotransferase, 2010). Aminoacyltransferases include gamma glutamyl transpeptidases and transglutaminase (tissue transglutaminase) (Wikipedia description of aminoacyltransferases, 2010)." (Id. at 14.) The 5 Appeal2013-003190 Application 12/016,266 Examiner concludes that it would be obvious to "to replace the cyclase gene of Yoshimura with mouse or human Qpct known in GenBank for basic research of Qpct function, i.e. studying the function of Qpct in vivo." (Id. at 7.) "Qpct is a member of the family of aminoacyltransferases .... Aminoacyltransferases include gamma glutamyl transpeptidases and transglutaminase (tissue transglutaminase)." (Id. at 14.) According to the Examiner, the U.S. Patent No. 7,381,537 provides a "link between glutaminyl cyclase and Alzheimer's disease" (Id. at 14--15), and because of this link one of ordinary skill in the art would have been motivated to make the substitution between the Qpct known in GenBank and the cyclase of Yoshimura's transgenic mice. Appellants contend that the Examiner had not articulated a sufficient rationale for a finding obviousness. (See App. Br. 32-37) Appellants contend that "out of the vast number of aminoacyltransferase genes available in GenBank, the Office provides no reason or desirability (other than scientific curiosity) to specifically select Qpct for overexpression in a mouse." (Id. at 34 and 35.) Appellants contend that "'obvious to try' is an inappropriate rationale where the approach is in 'a promising field of experimentation [and] the prior art gave only' general guidance as to the particular form of the claimed invention or how to achieve it."' (Id. at 33, citing MPEP §2145(X)(B)). The issue is: Does the preponderance of evidence of record support the Examiner conclusion that substitution of a glutaminyl cyclase for an adenylyl cyclase is obvious based on the teachings of Yoshimura in conjunction with the gene bank sequences? 6 Appeal2013-003190 Application 12/016,266 Findings of Fact FF4. Yoshimura teaches the "involvement of cAMP-mediated events in the neuroadaptive phenomena leading to morphine tolerance and/or dependence." (Yoshimura, Abstract.) FF5. Yoshimura teaches that "[a]denylyl cyclases (ACs) constitute a family of enzymes that convert ATP to the intracellular second messenger cAMP. Nine A Cs have been cloned and characterized to date, and each isoform has a particular regulatory characteristic that distinguishes it from the others." (Yoshimura 1011.) FF6. The Examiner finds that "Yoshimura taught homozygous and heterozygous transgenic mice whose genome comprised a nucleic acid sequence encoding a cyclase gene operably linked to a brain specific promoter." (Ans. 6; see also Yoshimura 1011.) Principle of Law "An examiner bears the initial burden of presenting a prima facie case of obviousness." In re Huai-Hung Kao, 639 F.3d 1057, 1066 (Fed. Cir. 2011. In satisfying this initial burden, "[i]t is impermissible to use the claimed invention as an instruction manual or 'template' to piece together the teachings of the prior art so that the claimed invention is rendered obvious." In re Fritch, 972 F.2d 1260, 1266 (Fed. Cir. 1992). Stated differently, to establish obviousness, there must be "an apparent reason to combine the known elements in the fashion" recited in the claims. KSR Int 'l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007). Analysis The Examiner's prima facie rejection is based on Yoshimura in conjunction with two GenBank sequences. Yoshimura teaches the 7 Appeal2013-003190 Application 12/016,266 production of transgenic animals that express adenylyl cyclases (ACs) in the brain (FF4-FF6) of the transformed animals. The Examiner's rationale is that it would be obvious to substitute any cyclase for the cyclase disclosed Yoshimura in order to "to study the role of Qpct in Alzheimer's as Qpct had already been linked to Alzheimer's disease." (Ans. 7.) According to the Examiner, "the desire to study the function of Qpct in vivo is more than a 'scientific curiosity' ... ; it is basic research of the function of Qpct in vivo." (Final Act. 21.) In the rebuttal, the Examiner expands on the stated rationale by supplying additional references4 in an effort to establish a link between Qpct levels and Alzheimer's disease as a reason to pick the two GenBank sequences (see Final Act. 20-22; Ans. 13-19). Appellants contend that the Examiner cites an additional five references to support the Examiner's position that one would have been motivated to replace the cyclase gene of Yoshimura with mouse or human Qpct known in GenBank. "The Office asserts it is obvious to overexpress 'any' aminoacyltransferase and that motivation lays in 'basic research' of Qpct function and is more than a 'scientific curiosity"' (App. Br. 35; see Reply Br. 10.) Appellants position is that there are no teachings "that would have motivated selection of species Qpct from the genus of aminoacylcyclases." (App. Br. 36.) 4 Ikeda (JP 2005-124402); Tucholski (Tissue transglutaminase overexpression in the brain potentiates calcium-induced hippocampal damage, 97 J. Neurochemistry 582-594 (2006)), Aminoacyltransferase, http://en.wikipedia.org/wiki/ Aminoacyltransferase (last accessed Jan. 4, 2011 ), glutaminyl-peptide cyclotransferase, http://en.wikipedia.org/wiki/Glutaminyl-peptide_cyclotransferase (last accessed Jan. 4, 2011) (cited on form 892 mailed April, 4, 2011), and U.S. Pat. No. 7,381,537 (cited on IDS filed Sept. 30, 2009). 8 Appeal2013-003190 Application 12/016,266 We find that Appellants have the better position. Here, the Examiner is relying on references that are not included in the statement of rejection under 35 U.S.C. § 103(a) in supporting the rejection. According to the Examiner, these references were cited to disclose "a link between glutaminyl cyclase and Alzheimer's disease; ... [including] a method of treating Alzheimer's disease by administering to a mammal in need thereof an inhibitor of glutaminyl cyclase or a pharmaceutically acceptable salt thereof' (Ans. 14). The Examiner argues that "Qpct is a member of the family of aminoacyltransferases . . . . Aminoacyltransferases include gamma glutamyl transpeptidases and transglutaminase (tissue transglutaminase )" (id.). The Examiner mentions that Tucholski "made transgenic mice overexpressing tissue transglutaminase (an aminoacyltransferase) using a neural specific promoter" (id.). The Examiner concludes that "the desire to specifically pick Qpct for further research was readily apparent, and the desire to specifically study the function of Qpct in vivo is more than a 'scientific curiosity"' (Ans. 14.) In other words, here the Examiner is relying on the additional references to establish that there is a reason to pick Qpct out of all the possible cyclases found in GenBank and use that particular Qpct to substitute for the cyclase in Yoshimura. At this juncture, we think it appropriate to remind the Examiner that references relied on to support a rejection under 35 U.S.C. § 103 should be included in the statement of rejection. As stated in In re Hoch, 428 F.2d 1341, 1342 n.3 (CCPA 1970); see also MPEP 706.02(j). "Where a reference is relied on to support a rejection, whether or not in a 'minor capacity,' there would appear to be no excuse for not positively including the reference in the statement of the rejection. Where, as here, the Examiner lists three 9 Appeal2013-003190 Application 12/016,266 references "relied upon in the rejection of claims under appeal" and includes those references, and only those references, in the statement of rejection under 35 U.S.C. § 103, we have limited our review of the prima facie case of obviousness to those references. We shall not discuss the other references, referred to in the Examiner's Answer, further. We conclude that the preponderance of the evidence of record does not support the Examiner's conclusion that the combination of Yoshimura, and GenBank Accession No: NM_Ol 7659 (human) or NM_027455 (mouse) discloses a transgenic mouse glutaminyl cyclase (Qpct). We, thus, reverse the rejections under 35 U.S.C. § 103(a) that rely on solely the of Yoshimura, and GenBank Accession No: NM_Ol 7659 (human) or NM_027455 (mouse). SUMMARY We reverse the rejection of claims 42, 43, 49, and 50 under 35 U.S.C. § 112, as containing new matter that was not described in the Specification as filed. We reverse the rejection of claims 1-3, 5-15, 17-24, 34, and 42-50 under 35 U.S.C. § 103(a) over Yoshimura in view of GenBank Accession No: NM_Ol 7659 (human) or NM_027455 (mouse). REVERSED 10 Copy with citationCopy as parenthetical citation