DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-20 are pending and will be examined.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on January 17, 2025 and August 12, 2025 and was filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-4, 7-14 and 17-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Andersen et al. (US Patent 8,323,897; December 2012) in view of Dennis et al. (US Patent 6927028; August 2005).
With regard to claim 1, Andersen teaches method for preparing a preparation of amplified DNA from a biological sample of a first individual useful for measuring DNA from a second individual, the method comprising:
isolating cell-free DNA from the biological sample;
preparing a preparation of amplified DNA by amplifying a plurality of SNP loci from the isolated cell-free DNA or DNA derived therefrom in a single reaction volume;
analyzing the preparation of amplified DNA by high-throughput sequencing to obtain genetic data for the plurality of SNP loci, and measuring DNA from the second individual based on allele frequencies in the genetic data obtained (Example 8 where whole blood is used for amplification and analysis and included analysis of SNPs using real time amplification and further analysis).
With regard to claim 2, Andersen teaches the method of claim 1, wherein the biological sample is a blood sample (Example 8 where whole blood is used for amplification and analysis).
With regard to claim 3, Andersen teaches the method of claim 1, wherein the amplifying comprises universal amplification (col. 5 and col. 11 where both universal and targeted PCR are described).
With regard to claim 4, Andersen teaches the method of claim 1, wherein the amplifying comprises targeted amplification (col. 5 and col. 11 where both universal and targeted PCR are described).
With regard to claim 7, Andersen teaches the method of claim 1, wherein the target loci comprise at least 70 SNP loci (col. 5 where multiple SNPs are detected).
With regard to claim 8, Andersen teaches the method of claim 1, wherein the confidence that each SNP is correctly called is at least 95% (col. 5 where multiple SNPs are detected).
With regard to claim 9, Andersen teaches the method of claim 1, wherein the confidence that each SNP is correctly called is at least 99% (col. 5 where multiple SNPs are detected).
With regard to claim 10, Andersen teaches the method of claim 1, further comprising normalizing the genetic data for differences in amplification and/or measurement efficiency between the loci (col. 14 where efficiency is determined).
With regard to claim 11, Andersen teaches a method for preparing a high-throughput sequencing library from a sample comprising DNA:
isolating cell-free DNA from a blood sample, amplifying a plurality of SNP loci from the isolated cell-free DNA in a single reaction volume to obtain a preparation of amplification products, hybridizing a probe at each of the SNP loci of the amplification products, and using high-throughput sequencing to measure at least 100 SNP loci of the amplification products, wherein the isolated cell-free DNA comprises DNA from the first individual and DNA from the second individual (Example 8 where whole blood is used for amplification and analysis and included analysis of SNPs using real time amplification and further analysis).
With regard to claim 12, Andersen teaches the method of claim 11, wherein the amplifying comprises universal amplification (col. 5 and col. 11 where both universal and targeted PCR are described).
With regard to claim 13, Andersen teaches the method of claim 11, wherein the amplifying comprises targeted amplification (col. 5 and col. 11 where both universal and targeted PCR are described).
With regard to claim 14, Andersen teaches the method of claim 11, wherein the amplifying comprises whole genome amplification (col. 5 and col. 11 where both universal and targeted PCR are described).
With regard to claim 17, Andersen teaches the method of claim 11, wherein each probe is arranged in an array (col 3 and col. 5).
With regard to claim 18, Andersen teaches the method of claim 11, wherein each probe is a molecular inversion probe (MIP) (col 3 and col. 5).
With regard to claim 19, Andersen teaches the method of claim 11, wherein measuring the at least 100 SNP loci comprises measuring a signal associated with a nucleotide for each of the SNP loci in the amplification products (col. 5 where multiple SNPs are detected).
With regard to claim 20, Andersen teaches the method of claim 11, wherein the at least 100 SNP loci are from at least two genes of the DNA from the first individual and DNA from the second individual (col. 5 where multiple SNPs are detected).
Regarding claim 1 and 11, while Andersen teaches the method of amplification and sequencing as claimed, Andersen does not teach the method of isolating cell-free DNA particularly.
With regard to claim 1, Dennis teaches isolating cell-free DNA from the biological sample, wherein the biological sample comprises DNA from the first individual and DNA from the second individual (Abstract; col. 2 and 5, where individuals are distinguished using DNA; see also Fig 3 and 4).
With regard to claim 11, Dennis teaches a method comprising DNA from a first individual and a second individual, the method comprising: isolating cell-free DNA from a blood sample of the first individual (Abstract; col. 2 and 5, where individuals are distinguished using DNA; see also Fig 3 and 4).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have adjusted the teachings of Andersen to include the isolation of cell free DNA as taught by Dennis to arrive at the claimed invention with a reasonable expectation for success. Andersen teaches the method as claimed but does not teach the step of isolation, while Dennis is focused particularly on isolation of cell free nucleic acids and distinguishing individuals within those samples. In particular, Dennis states “In a first aspect, the present invention features methods for differentiating DNA species originating from different individuals in a biological sample. In preferred embodiments the methods of the present invention are used to differentiate or detect fetal DNA in a maternal sample or to differentiate DNA of an organ donor from DNA of an organ recipient” (col. 2). Therefore, one of ordinary skill in the art at the time the invention was made would have adjusted the teachings of Andersen to include the isolation of cell free DNA as taught by Dennis to arrive at the claimed invention with a reasonable expectation for success.
Claim(s) 5 and 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Andersen et al. (US Patent 8,323,897; December 2012) in view of Dennis et al. (US Patent 6927028; August 2005) as applied over claims 1-4, 7-14 and 17-20 above and further in view of Mueller et al. (Science, 1989, 246:780–786).
With regard to claim 5, Mueller teaches the method of claim 1, wherein the amplifying comprises ligation-mediated PCR (Abtract and Figure 1).
With regard to claim 15, Mueller teaches the method of claim 11, wherein the amplifying comprises ligation-mediated PCR (Abtract and Figure 1).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have adjusted the teachings of Andersen and Dennis to include ligation mediated PCR as taught by Mueller to arrive at the claimed invention with a reasonable expectation for success. Each of Andersen, Dennis and Mueller are focused on nucleic acid analysis. Mueller is focused in particular on ligation mediated PCR amplification. Mueller teaches “This ligation mediated, single-sided PCR technique permits the exponential amplification of an entire sequence ladder. Several footprints were detected in terminally differentiated muscle cells where the MCKgene is actively transcribed.” (Abstract). Therefore, one of ordinary skill in the art at the time the invention was made would have adjusted the teachings of Andersen and Dennis to include ligation mediated PCR as taught by Mueller to arrive at the claimed invention with a reasonable expectation for success.
Claim(s) 6 and 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Andersen et al. (US Patent 8,323,897; December 2012) in view of Dennis et al. (US Patent 6927028; August 2005) as applied over claims 1-4, 7-14 and 17-20 above and further in view of Marguiles et al. (Nature, 2005, 15; 437(7056):376-380).
With regard to claim 6, Marguiles teaches the method of claim 1, wherein the high-throughput sequencing comprises sequencing- by-synthesis (p 27-29 of supplementary method steps, where the sequencing method steps are described; p. 2 of reference where the method is pyrosequencing which is a sequencing by synthesis method).
With regard to claim 16, Marguiles teaches the method of claim 11, wherein the high-throughput sequencing comprises sequencing- by-synthesis (p 27-29 of supplementary method steps, where the sequencing method steps are described; p. 2 of reference where the method is pyrosequencing which is a sequencing by synthesis method).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have adjusted the teachings of Andersen and Dennis to include the pyrosequencing method taught by Margulies to arrive at the claimed invention with a reasonable expectation for success. Each of Andersen, Dennis and Margulies focus on analysis of nucleic acids. Andersen is focused on detection of specific SNPs using multiplex amplification of cell free nucleic acids while Margulies focuses on sequencing in reactors. Margulies teaches “We describe a scalable, highly parallel sequencing system with raw throughput significantly greater than that of state-of-the-art capillary electrophoresis instruments. The apparatus uses a novel 60×60mm2 fibreoptic slide containing 1,600,000 individual wells and is able to sequence 25 million bases, at 99% or better accuracy (phred 20), in a 4 hour run”. Therefore, one of ordinary skill in the art at the time the invention was made would have adjusted the teachings of Andersen and Dennis to include the pyrosequencing method taught by Margulies to arrive at the claimed invention with a reasonable expectation for success.
Conclusion
No claims are allowed. All claims stand rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEPHANIE KANE MUMMERT whose telephone number is (571)272-8503. The examiner can normally be reached M-F 9:00-5:30.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gary Benzion can be reached at 571-272-0782. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/STEPHANIE K MUMMERT/Primary Examiner, Art Unit 1681
Prosecution Insights