12130818 (P.T.A.B. Nov. 7, 2013)

Ex Parte Buelow

Patent Trial and Appeal BoardNov 7, 2013

12130818 (P.T.A.B. Nov. 7, 2013)

UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte ROLAND BUELOW ____________ Appeal 2012-008014 Application 12/130,818 Technology Center 1600 ____________ Before LORA M. GREEN, MELANIE L. McCOLLUM and ANNETTE R. REIMERS, Administrative Patent Judges. REIMERS, Administrative Patent Judge. DECISION ON APPEAL Appeal 2012-008014 Application 12/130,818 2 STATEMENT OF THE CASE1 Roland Buelow (Appellant)2 appeals under 35 U.S.C. § 134(a) from the Examiner’s decision to reject claims 14-22 and 35-39. We have jurisdiction over this appeal under 35 U.S.C. § 6(b). We REVERSE. CLAIMED SUBJECT MATTER Appellant’s invention “relates to transgenic animals having one or more inactivated endogenous immunoglobulin loci” (Spec. 1, para. [002]). Claim 14 is representative and reads as follows: 14. A viable rodent germ cell having at least one endogenous immunoglobulin (Ig) gene inactivated by the action of at least one meganuclease. THE EVIDENCE The Examiner relies on the following references in rejecting the appealed claims: Kucherlapati (‘205) US 5,574,205 Nov. 12, 1996 Kucherlapati (‘598) US 5,939,598 Aug. 17, 1999 Kucherlapati (‘181) US 6,075,181 Jun. 13, 2000 Kucherlapati (‘598*) US 6,114,598 Sep. 5, 2000 Kucherlapati (‘835) US 6,139,835 Oct. 31, 2000 Kucherlapati (‘584) US 6,150,584 Nov. 21, 2000 Kucherlapati (‘963) US 6,162,963 Dec. 19, 2000 Buelow (‘534) US 2003/0017534 A1 Jan. 23, 2003 Kucherlapati (‘752) US 6,514,752 B1 Feb. 4, 2003 1 Claims 1-13, 23-34, 40 and 41 have been canceled. 2 The real party in interest is OMT, Inc. Appeal 2012-008014 Application 12/130,818 3 Kucherlapati (‘103) US 6,657,103 B1 Dec. 2, 2003 Kucherlapati (‘986) US 6,673,986 B1 Jan. 6, 2004 Kucherlapati (‘610) US 6,713,610 B1 Mar. 30, 2004 Buelow (‘880) US 2004/0158880 A1 Aug. 12, 2004 Buelow (‘392) US 2005/0153392 A1 Jul. 14, 2005 Buelow (‘263) US 2005/0229263 A1 Oct. 13, 2005 Buelow (‘696) US 2006/0026696 A1 Feb. 2, 2006 Buelow (‘398) US 2006/ 0117398 A1 Jun. 1, 2006 Jakobovits (‘244) US 7,064,244 B2 Jun. 20, 2006 Arnould (‘826) US 2006/0153826 A1 Jul. 13, 2006 Arnould (‘949) US 2006/0206949 A1 Sep. 14, 2006 Buelow (‘084) US 7,129,084 B2 Oct. 31, 2006 Buelow (‘668) US 7,585,668 B2 Sep. 8, 2009 Jakobovits (‘893) WO 98/24893 Jun. 11, 1998 Schooten WO 02/12437 A2 Feb. 14, 2002 Buelow (‘001) WO 2005/038001 A2 Apr. 28, 2005 M. H. Porteus and D. Carroll, Gene targeting using zinc fingernucleases, 23 NATURE BIOTECHNOLOGY 967-973 (2005). Vasquez et al., Manipulating the mammalian genome by homologous recombination, 98 PNAS 8403-8410 (2001). Donoho et al., Analysis of Gene Targeting and Intrachromosomal Homologous Recombination Stimulated by Genomic Double-Strand Breaks in Mouse Embryonic Stem Cells, 18 MOLECULAR AND CELLULAR BIOLOGY 4070-4078 (1998). Cohen-Tannoudji et al., I-SceI-Induced Gene Replacement at a Natural Locus in Embryonic Stem Cells, 18 MOLECULAR AND CELLULAR Appeal 2012-008014 Application 12/130,818 4 BIOLOGY 1444-1448 (1998). Pabo et al., DESIGN AND SELECTION OF NOVEL CYS2HIS2 ZINC FINGER PROTEINS, 70 ANNU. REV. BIOCHEM. 313-340 (2001). M. Isalan and Y. Choo, Rapid, High-Throughput Engineering of Sequence-Specific Zinc Finger DNA-Binding Proteins, 340 METHODS IN ENZYMOLOGY 593-609 (2001). Definition of the word “germ cell” (Online Free Medical Dictionary definition of “germ cell”, 2010). Appellant presents additional evidence in the Declarations filed under 37 C.F.R. § 1.132 of Dr. Ina Dobrinski,3 Dr. Andrew M. Scharenberg,4 and Dr. Eckhard Wolf,5 all of which were filed November 15, 2011. THE REJECTION The following rejection is before us for review: Claims 14-22 and 35-39 stand rejected under 35 U.S.C. § 103(a) as unpatentable over Kucherlapati (‘205), Kucherlapati (‘598), Kucherlapati (‘181), Kucherlapati (‘598*), Kucherlapati (‘835), Kucherlapati (‘584), Kucherlapati (‘963), Kucherlapati (‘752), Kucherlapati (‘103), Kucherlapati (‘986), Kucherlapati (‘610), Jakobovits (‘244), Jakobovits (‘893), Schooton, Buelow (‘534), Buelow (‘880), Buelow (‘392), Buelow (‘263), Buelow (‘001), Buelow (‘696), Buelow (‘398), Buelow (‘084), Buelow (‘668), or Arnould (‘826), Arnould (‘949), Porteus, Vasquez, Donoho, or Cohen- Tannoudji, Pabo, Isalan and the definition of “germ cell”. 3 Hereafter the “Dobrinski Declaration”. 4 Hereafter the “Scharenberg Declaration”. 5 Hereafter the “Wolf Declaration”. Appeal 2012-008014 Application 12/130,818 5 ANALYSIS Independent claim 14 recites “[a] viable rodent germ cell having at least one endogenous immunoglobulin (Ig) gene inactivated by the action of at least one meganuclease” (App. Br., Clms. App’x.). In rejecting the claims, the Examiner offers two different theories as to why the cited references render the claimed germ cell obvious. Under the first theory, the Examiner finds that Kucherlapati, Jakobovits, Schooten, Buelow and Arnould (‘826) (i.e., the first 24 references cited) taught methods of inactivating endogenous V (variable), J (joining) and C (constant) Ig (immunoglobulin) genes of mice and humanizing the immunoglobulin gene to make human V, J and C IG gene products. The mice whose genomes have an inactivated IgG gene implicitly comprise egg and sperm having an inactivated IgG gene further comprising the human immunoglobulin gene as indicated by reproduction of the mice and germline transmission of the inactivated, humanized Ig gene (Ans. 7). Further, according to the Examiner, [t]he first 24 references are not limited to ES cells with an inactivated Ig gene inactivated because they also taught transgenic mice whose genomes have an inactivated IgG gene which inherently comprise egg and sperm having an inactivated IgG gene further comprising the human immunoglobulin gene as evidenced by germline transmission of the inactivated, humanized Ig gene to [the] offspring (Ans. 16). Appeal 2012-008014 Application 12/130,818 6 In the second theory, the Examiner takes the position that ES [Embryonic Stem] cells are “germ cells” because the term “germ cell” is defined as an ovum or sperm cell or one of their developmental precursors (see definition of “germ cell” provided, Free Online Medical Dictionary, 2010), because the term in the [S]pecification includes germ cells and “precursors thereof” (pg 20, paragraph 140), . . . Since ES cells become entire mice including egg/sperm, they are “precursors” of egg/sperm. Accordingly, the broadest reasonable interpretation of “germ cell” encompasses ES cells because they are germ line cells capable of becoming egg or sperm (Ans. 17-18). As such, the Examiner finds that “the ES cells with the inactivated Ig genes used to make the transgenic mice taught in the first 24 references are also considered ‘germ cells’ as claimed” (Ans. 8). In reference to either the first or second theory, the Examiner finds that “[t]he first 24 references cited in the paragraph above did not teach the endogenous V, J and C Ig genes were inactivated in germ cells by meganuclease” (Ans. 8). The Examiner further finds that “using meganuclease to inactivate genes in ES cells was well known in the art at the time of filing” as described by Donoho, Cohen-Tannoudji, Porteus and Vasquez (Ans. 8). The Examiner concludes that it would have been obvious to those of ordinary skill in the art at the time the invention was made to inactivate an endogenous Ig gene in an ES cell as described by the first 24 references cited using meganuclease as described by Arnould, Porteus, Vasquez, Donoho, or Cohen-Tannoudji. The advantages of using meganuclease are discussed Appeal 2012-008014 Application 12/130,818 7 on pg 1447, Fig. 4 and col. 2, lines 10-22, of Cohen-Tannoudji and throughout the secondary references, i.e. increased targeting (Ans. 9). In response to the Examiner’s second theory, Appellant contends that interpreting the definition of “germ cell” provided by the cited Free Online Medical Dictionary as encompassing an embryonic stem cell is clearly erroneous because such characterization can only occur if the Office (1) inappropriately dismisses unrefuted fact evidence that the customary meaning of “germ cell” given by those of ordinary skill in the art does not encompass an embryonic stem cell and (2) also improperly disregards the fact that the proposed interpretation is inconsistent with Appellant’s use of the term in the [S]pecification (App. Br. 11). Appellant’s arguments are persuasive. Appellant’s Specification does not expressly define the term “germ cell” or otherwise indicate that this term is used in a manner other than its ordinary and customary meaning. The Specification does describe that “[i]n one embodiment, the method involves transfecting germ cells, which may include precursors thereof such as spermatagonial stem cells” (Spec. 20, para. [00140]). We agree with Appellant that an ordinary and customary meaning of the term “germ cell”6 is “a sexual reproduction cell” (see App. Br. 11), which is consistent with Appellant’s use of this term in the Specification. We further agree with Appellant that a skilled artisan would recognize that “precursors of germ 6 An ordinary and customary meaning of the term “germ cell” is “a gamete (as an egg or sperm cell) or one of its antecedent cells” MERRIAM WEBSTER’S COLLEGIATE DICTIONARY (11th ed. 2005). Appeal 2012-008014 Application 12/130,818 8 cells encompass the entire germ cell lineage from primordial germ cells, gonia, and all subsequent differentiating germ cells up to the spermatozoa and oocytes” and “[a]n embryonic stem cell would not be considered a primordial germ cell [by a skilled artisan] since an embryonic stem cell is not a sexual reproductive cell” (App. Br. 12; see also Dobrinski Declaration ¶¶ 6-7). Consequently, we agree with Appellant that “the plain meaning of the term ‘germ cell,’ in light of the [S]pecification as it would be interpreted by one of ordinary skill in the art, would not encompass an embryonic stem cell” (App. Br. 12). Thus, we find the Examiner’s interpretation of the term “germ cell” to encompass an “embryonic stem cell” to be unreasonable in light of the claim and the Specification. See In re Cortright, 165 F.3d 1353, 1358 (Fed. Cir. 1999) (“Although the PTO must give claims their broadest reasonable interpretation, this interpretation must be consistent with the one that those skilled in the art would reach”). In response to the Examiner’s first theory, Appellant contends that the “inherent” germ cell asserted as prior art against the instant claims can only result from the otherwise unsupported combination of different prior art teachings to produce a theoretical embyronic stem cell, which could develop further into a theoretical transgenic animal, which might then have a theoretical germ cell asserted as prior art, and all of which ignores the considerable scientific uncertainties widely recognized and explicitly acknowledged by skilled artisans with such an approach (App. Br. 16). Appellant further contends that the first 24 references show that germ line transmission of an inactivated gene from an animal cultivated from a modified embyronic stem cell Appeal 2012-008014 Application 12/130,818 9 occurs only occasionally, and further, [] Donoho, Cohen-Tannoudji, Porteus and Vasquez do not teach mice with genes inactivated by a meganuclease. Accordingly, there is no basis to support the hypothesis that meganuclease mediated gene inactivation in an embryonic stem cell will necessarily result in germline transmission of the inactivation upon cultivation of the ES cell into an animal (App. Br. 17). The Examiner’s first theory is premised on the finding that transgenic mice that comprise a genome having an IgG gene inactivated by a meganuclease, would inherently comprise egg and sperm having an inactivated IgG gene (Ans. 16). However, the Examiner has not established with any evidence or provided any explanation on this record that reproduction of transgenic mice in any of the first 24 prior art references would inevitably, or necessarily, result in germline transmission of the inactivated, humanized Ig gene to the offspring, such that the inactivated, humanized gene necessarily is present in the germ cells of the offspring. “Inherency . . . may not be established by probabilities or possibilities. The mere fact that a certain thing may result from a given set of circumstances is not sufficient.” MEHL/Biophile Int’l. Corp. v. Milgraum, 192 F.3d 1362, 1365 (Fed. Cir. 1999). “An inherent characteristic must be inevitable, and not merely a possibility or probability.” See In re Oelrich, 666 F.2d 578, 581 (CCPA 1981). The Examiner has not satisfied the initial burden of presenting a prima facie case of obviousness. Accordingly, we are constrained to reverse the Examiner’s rejection of claims 14-22 and 35-39 under 35 U.S.C. § 103(a) as unpatentable over Kucherlapati (‘205), Kucherlapati (‘598), Kucherlapati Appeal 2012-008014 Application 12/130,818 10 (‘181), Kucherlapati (‘598*), Kucherlapati (‘835), Kucherlapati (‘584), Kucherlapati (‘963), Kucherlapati (‘752), Kucherlapati (‘103), Kucherlapati (‘986), Kucherlapati (‘610), Jakobovits (‘244), Jakobovits (‘893), Schooton, Buelow (‘534), Buelow (‘880), Buelow (‘392), Buelow (‘263), Buelow (‘001), Buelow (‘696), Buelow (‘398), Buelow (‘084), Buelow (‘668), or Arnould (‘826), Arnould (‘949), Porteus, Vasquez, Donoho, or Cohen- Tannoudji, Pabo, Isalan and the definition of “germ cell”.7 DECISION We REVERSE the decision of the Examiner to reject claims 14-22 and 35-39. REVERSED Klh 7 Because we have determined that the Examiner failed to establish a prima facie case of obviousness, we do not reach the evidence of secondary considerations of non-obviousness of the Scharenberg and Wolf Declarations.