10399899 (B.P.A.I. Jul. 27, 2011)

Ex Parte Guldberg

Board of Patent Appeals and InterferencesJul 27, 2011

10399899 (B.P.A.I. Jul. 27, 2011)

UNITED STATES PATENT AND TRADEMARKOFFICE 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. 10/399,899 10/03/2003 Per Guldberg 026419-0104 7548 22428 7590 07/27/2011 FOLEY AND LARDNER LLP SUITE 500 3000 K STREET NW WASHINGTON, DC 20007 EXAMINER CHUNDURU, SURYAPRABHA ART UNIT PAPER NUMBER 1637 MAIL DATE DELIVERY MODE 07/27/2011 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 BOARD OF PATENT APPEALS AND INTERFERENCES ____________ Ex parte PER GULDBERG ____________ Appeal 2010-006189 Application 10/399,899 Technology Center 1600 ____________ Before DONALD E. ADAMS, ERIC GRIMES, and JEFFREY N. FREDMAN, Administrative Patent Judges. ADAMS, Administrative Patent Judge. DECISION ON APPEAL This appeal under 35 U.S.C. § 134 involves claims 1-5, 7-10, and 12- 15 (App. Br. 3).1 We have jurisdiction under 35 U.S.C. § 6(b). STATEMENT OF THE CASE The claims are directed to a method of determining a methylation profile for a target nucleic acid sequence (claims 1-5 and 7) and a method of determining the existence of a nucleic acid methylation profile associated with a disease state, using a test nucleic acid from a candidate disease cell 1 Claims 16-27 stand withdrawn from consideration (App. Br. 3). Appeal 2010-006189 Application 10/399,899 2 (claims 8-10 and 12-15). Claim 1 is representative and is reproduced in the “CLAIMS APPENDIX” of Appellant’s Brief (App. Br. 10). Claims 1-3, 7-9, and 12-15 stand rejected under 35 U.S.C. § 103(a) as unpatentable over the combination of Navot2 and Elenitoba-Johnson.3 Claims 4 and 10 stand rejected under 35 U.S.C. § 103(a) as unpatentable over the combination of Navot, Elenitoba-Johnson and Markowitz.4 Claim 5 stands rejected under 35 U.S.C § 103(a) as unpatentable over the combination of Navot, Elenitoba-Johnson and Crouzet.5 We reverse. PRINCIPLES OF LAW An invention composed of several elements is not proved obvious merely by demonstrating that each of its elements was, independently, known in the prior art. . . . [I]t can be important to identify a reason that would have prompted a person of ordinary skill in the relevant field to combine the elements in the way the claimed new invention does. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007). The combination of Navot and Elenitoba-Johnson: ISSUE Does the preponderance of evidence on this record support a conclusion of obviousness? 2 Navot et al., US 6,335,165 B1, issued January 1, 2002. 3 Elenitoba-Johnson, US 6,346,386 B1, issued February 12, 2002. 4 Markowitz et al., US 6,858,388 B2, issued February 22, 2005. 5 Crouzet et al., US 6,410,273 B1, issued June 25, 2002. Appeal 2010-006189 Application 10/399,899 3 FACTUAL FINDINGS FF 1. Navot’s invention “relates to methods and kits for amplification, size determination and sequencing of GC rich nucleic acid sequences” (Navot, col. 1, ll. 9-11). FF 2. Navot’s method includes (a) contacting a nucleic acid of interest with an agent that modifies cytosine or guanine residues, (b) amplifying the modified nucleic acid; and (c) determining the size of the amplification product, thereby characterizing the GC rich region of the nucleic acid of interest (Navot, Abstract; see also Navot, col. 6, ll. 46-61; see generally Ans. 3). FF 3. The modifying agent in step (a) of Navot’s method can be a demethylating agent or an agent “effective in modifying cytosine residues (either methylated or unmethylated) into residues complementary to adenine” (Navot, col. 8, ll. 42 and 54-56). FF 4. Navot suggests that the modifying agent may be “bisulfite which modifies unmethylated cytosine residues into uracil residues” (Navot, col. 9, ll. 2-4; see generally Ans. 3). FF 5. “Size determination according to . . . [Navot’s] invention can be effected in a variety of ways, including, but not limited to, gel electrophoresis” (Navot, col. 10, ll. 62-64). FF 6. Elenitoba-Johnson suggests “[a] method for determining whether a DNA sequence is identical to a wild-type sequence” (Elenitoba-Johnson, Abstract; see Ans. 3-4). FF 7. According to Elenitoba-Johnson’s method “[t]he melting temperature of the DNA segment of interest is compared to the melting point of the wild-type sequence. A difference in melting temperatures of the DNA Appeal 2010-006189 Application 10/399,899 4 sequence and the wild-type sequence indicates an alteration in the DNA sequence” (id.; see also Ans. 3-4). ANALYSIS Based on the combined teachings of Navot and Elenitoba-Johnson the Examiner concludes that “[i]t would have been prima facie obvious to a person of ordinary skill in the art at the time the invention was made to modify the method of determining methylation profile as taught by Navot et al. in a manner as taught by Elenitoba-Johnson” (Ans. 4). We are not persuaded. Notwithstanding the Examiner’s assertion to the contrary, we agree with Appellant’s contention that “Navot’s entire disclosure focuses on the characterization of the length of CGG repeats, not gene methylation” (Reply Br. 4; see FF 1-2). We also agree with Appellant’s contention that “[n]othing in Navot implicates determining a methylation profile of a target nucleic acid, let alone resolving heterogeneous methylation patterns, as the appealed claims prescribe” (id.). We agree with Appellant’s contention that “Elenitoba-Johnson discloses the detecting not of alterations in methylation pattern, as in . . . [Appellant’s] claimed invention, but rather of alterations in DNA sequence, i.e., base-pair changes” (id.). Accordingly, Elenitoba-Johnson fails to make up for the deficiency in Navot. At best, the references relied upon by the Examiner suggest various elements of Appellant’s claimed invention, however, taken together they fail to suggest the combination of elements in the manner set forth in Appellant’s claimed invention. See KSR, 550 U.S. at 418. Appeal 2010-006189 Application 10/399,899 5 CONCLUSION OF LAW The preponderance of evidence on this record fails to support a conclusion of obviousness. The rejection of claims 1-3, 7-9, and 12-15 under 35 U.S.C § 103(a) as unpatentable over the combination of Navot and Elenitoba-Johnson is reversed. The combination of Navot, Elenitoba-Johnson and Markowitz: ISSUE Does the preponderance of evidence on this record support a conclusion of obviousness? FACTUAL FINDINGS FF 8. The combination of Navot and Elenitoba-Johnson is addressed above. FF 9. Markowitz suggests a method that Comprises reacting DNA from . . . [a sample of bodily fluid] with a chemical compound [(e.g., sodium bisulfite)] that converts non-methylated cytosine bases . . ., but not methylated cytosine bases, to a different nucleotide base. . . . The compound-converted DNA is then amplified using a methylation-sensitive polymerase chain reaction (MSP) employing primers that amplify the compound-converted DNA template if cytosine bases within CpG dinucleotides of the DNA from the sample are methylated. Production of a PCR product indicates that the subject has a cancer associated with methylation of hMLH1 promoter DNA. (Markowitz, col. 2, ll. 4-19; see generally Ans. 5.) Appeal 2010-006189 Application 10/399,899 6 ANALYSIS Based on the combined teachings of Navot, Elenitoba-Johnson and Markowitz the Examiner concludes that It would have been prima facie obvious to a person of ordinary skill in the art at the time the invention was made to modify the method of determining methylation profile as taught by Navot et al. in view of Elenitoba-Johnson with the target nucleic acids from cancer disease as taught by Markowitz et al. to achieve an expected benefit of detecting methylation pattern in cancer. (Ans. 6.) Appellant’s claimed method requires, inter alia, that a converted nucleic acid sequence is amplified “using oligonucleotide primers specific only for said converted nucleic acid sequence, wherein said primers do not discriminate between methylated and unmethylated alleles” (see Appellant’s claims 1 and 8 (emphasis added)). In contrast, Markowitz suggests the amplification of compound-converted DNA “using a methylation-sensitive polymerase chain reaction (MSP) employing primers that amplify the compound-converted DNA template if cytosine bases within CpG dinucleotides of the DNA from the sample are methylated” (FF 9 (emphasis added)). Accordingly, Markowitz fails to make up for the deficiency in the combination of Navot and Elenitoba-Johnson. We, therefore, agree with Appellant’s contention that “no combination of the cited material yields a method of determining a methylation profile for a target nucleic acid sequence, as presently recited” in Appellant’s claims (App. Br. 8). Appeal 2010-006189 Application 10/399,899 7 CONCLUSION OF LAW The preponderance of evidence on this record fails to support a conclusion of obviousness. The rejection of claims 4 and 10 under 35 U.S.C § 103(a) as unpatentable over the combination of Navot, Elenitoba-Johnson and Markowitz is reversed. The combination of Navot, Elenitoba-Johnson and Crouzet: ISSUE Does the preponderance of evidence on this record support a conclusion of obviousness? FACTUAL FINDINGS FF 10. The combination of Navot and Elenitoba-Johnson is addressed above. FF 11. The Examiner finds that “neither Navot et al. nor Elenitoba-Johnson teach . . . [a target nucleic acid sequence] from a plant or prokaryotic organism” (Ans. 6). FF 12. Crouzet suggests a method that advantageously uses a bacterial cell host that “employs a host cell containing a cassette for the expression of a DNA methyltransferase that enables the cytosine residues of the dinucleotides 5’-CG-3’ to be methylated” (Crouzet, col. 4, l. 38 and col. 7, ll. 8-11). ANALYSIS While the Examiner asserts that “Crouzet et al. teach a bisulfite method for producing methylated DNA comprising target nucleic acids from prokaryotic organism[s] (see col. 4, line[s] 22-49),” we do not find a reference to bisulfite in the cited portion of Crouzet (see Ans. 6; Cf. Crouzet, Appeal 2010-006189 Application 10/399,899 8 col. 4, ll. 22-49). Nevertheless, we agree with Appellant’s contention that Crouzet “fails to cure the deficiencies noted for Navot and Elenitoba- Johnson” (App. Br. 9). CONCLUSION OF LAW The preponderance of evidence on this record fails to support a conclusion of obviousness. The rejection of claim 5 under 35 U.S.C § 103(a) as unpatentable over the combination of Navot, Elenitoba-Johnson and Crouzet is reversed. REVERSED cdc