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 .
The preliminary amendment filed March 14, 2024, amending claim 1 and adding new claims 2-20 is acknowledged and has been entered.
Claims 1-20 are pending and will be examined.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on March 14, 2024 was filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-33 of U.S. Patent No. 11854665 (‘665 patent herein). Although the claims at issue are not identical, they are not patentably distinct from each other because while the claims are not the same, they cover very similar subject matter. The primary difference between the claims of the ‘665 patent is that the instant claims include the amplification of a first and second plurality of loci, a first and second reference sequence and additional steps in the instant claim 1 regarding allelotyping and sequence counts. However, these additional steps of allelotyping (claim 10-11 of ‘665 patent) and sequence counts (claims 1 and 30-32 of ‘665 patent)are encompassed within the claim set of the ‘665 patent. Therefore, the instant claims are not patentable in view of the claims of the ‘665 patent.
Further, compare the targets to allelotype the DNA sample (instant claim 1 and claims 10-11 of the ‘665 patent) and compare the limitations of identifying tissue source (compare instant claim 19 and claim 19 of ‘665 patent), age, risk of disease, response to environmental signals, expression level among other states (instant claim 20 and claim 21-23 of the ‘665 patent). Therefore, the claims are not in condition for allowance or patentably distinct.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 3-8 and 12-18 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Deciu et al. (US PgPub 20130309666; August 2014).
With regard to claim 1, Deciu teaches a method comprising:
digesting a portion of a deoxyribonucleic acid (DNA) sample with a methylation- dependent endonuclease;
amplifying (i) a first plurality of loci of the digested portion of DNA sample using a multiplex polymerase chain reaction (PCR) to produce a first plurality of amplicons and
(ii) a second plurality of loci of an undigested portion of the DNA sample using a multiplex PCR to produce a second plurality of amplicons, at least one of the plurality of loci being a positive control locus that does not contain a restriction site for the methylation-dependent endonuclease (paragraph 158, where the method of fetal quantitation analysis includes a step of digestion based on methylation status; Hpa II is a methylation specific enzyme that is used, see paragraph 167; multiplex amplification and next generation or massively parallel sequencing are also included within this method, see paragraph 170-171);
sequencing the first plurality of amplicons and the second plurality of amplicons together using a massively parallel sequencing (MPS) instrument to generate a plurality of sequence reads; determining a sequence count for each of the first plurality of loci by comparing at least some of the plurality of sequence reads to a first plurality of reference sequences, each of the first plurality of reference sequences being associated with one of the first plurality of loci (multiplex amplification and next generation or massively parallel sequencing are also included within this method, see paragraph 170-171);
normalizing the sequence count for each of the plurality of loci to the sequence count of the positive control locus (Figure 7 legend which describes the process of normalizing counts to a specific genomic region; see also paragraph 241-248 which describes the count normalization process at length); and
identifying a trait associated with the DNA sample by applying a classification algorithm to the normalized sequence counts for each of the first plurality of loci:
determining a sequence count for each of the second plurality of loci by comparing at least some of the plurality of sequence reads to a second plurality of reference sequences, each of the second plurality of reference sequences being associated with an allelotype of one of the second plurality of loci (Figure 7 legend which describes the process of normalizing counts to a specific genomic region; see also paragraph 241-248 which describes the count normalization process at length); and
allelotyping the DNA sample based on the sequence counts for each of the second plurality of loci (Figure 7 legend which describes the process of normalizing counts to a specific genomic region; see also paragraph 241-248 which describes the count normalization process at length).
With regard to claim 3, Deciu teaches a method of claim 1, wherein the second plurality of amplicons contain single nucleotide polymorphisms (paragraph 160, where SNPs are included).
With regard to claim 4, Deciu teaches a method of claim 1, wherein the first plurality of loci and the second plurality of loci are identical (multiplex amplification and next generation or massively parallel sequencing are also included within this method, see paragraph 170-171).
With regard to claim 5, Deciu teaches a method of claim 1, wherein the first plurality of loci and the second plurality of loci are overlapping but not identical (multiplex amplification and next generation or massively parallel sequencing are also included within this method, see paragraph 170-171).
With regard to claim 6, Deciu teaches a method of claim 1, wherein the first plurality of loci and the second plurality of loci do not overlap (multiplex amplification and next generation or massively parallel sequencing are also included within this method, see paragraph 170-171).
With regard to claim 7, Deciu teaches a method of claim 1, the first plurality of amplicons and the second plurality of amplicons are produced using the same multiplex PCR (multiplex amplification and next generation or massively parallel sequencing are also included within this method, see paragraph 170-171).
With regard to claim 8, Deciu teaches a method of claim 7, wherein the multiplex PCR uses unlabeled primers (multiplex amplification and next generation or massively parallel sequencing are also included within this method, see paragraph 170-171).
With regard to claim 12, Deciu teaches a method of claim 1, further comprising: labelling each of the first plurality of amplicons and each of the second plurality of amplicons with a unique nucleotide index, prior to sequencing; and
de-multiplexing the plurality of sequence reads using the unique nucleotide indexes (multiplex amplification and next generation or massively parallel sequencing are also included within this method, see paragraph 170-171).
With regard to claim 13, Deciu teaches a method of claim 12, wherein: determining the sequence count for each of the first plurality of loci comprises comparing each sequence read indexed to the first plurality of amplicons to the first plurality of reference sequences; and determining the sequence count for each of the second plurality of loci comprises comparing each sequence read indexed to the second plurality of amplicons to the second plurality of reference sequences (Figure 7 legend which describes the process of normalizing counts to a specific genomic region; see also paragraph 241-248 which describes the count normalization process at length).
With regard to claim 14, Deciu teaches a method of claim 1, further comprising applying a quality filter to the plurality of sequence reads, prior to determining the sequence counts.
With regard to claim 15, Deciu teaches a method of claim 1, further comprising trimming each of the plurality of sequence reads above a predetermined length, prior to determining the sequence counts (paragraph 145, where specific lengths are described).
With regard to claim 16, Deciu teaches a method of claim 1, wherein the methylation-dependent endonuclease is Hhal (HhaI and Hpa II are methylation specific enzyme that is used, see paragraph 167).
With regard to claim 17, Deciu teaches a method of claim 1, wherein: one of the first plurality of loci is a positive control locus that does not contain a restriction site for the methylation-dependent endonuclease (paragraph 158, where the method of fetal quantitation analysis includes a step of digestion based on methylation status; Hpa II is a methylation specific enzyme that is used, see paragraph 167; multiplex amplification and next generation or massively parallel sequencing are also included within this method, see paragraph 170-171); and
the method further comprises normalizing the sequence count for each of the first plurality of loci to the sequence count of the positive control locus prior to applying the classification algorithm (Figure 7 legend which describes the process of normalizing counts to a specific genomic region; see also paragraph 241-248 which describes the count normalization process at length).
With regard to claim 18, Deciu teaches a method of claim 17, wherein another of the first plurality of loci is a negative control locus that is substantially digested by the methylation-dependent endonuclease irrespective of the trait associated with the DNA sample (Example 5, where negative control, positive control and other aspects of sample criteria are taught).
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) 2, 9-11 and 19-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Deciu et al. US PgPub 20130309666; August 2014) as applied over claims 1, 3-8 and 12-18 above and further in view of Wasserstrom et al. (WO2011070441; June 2011).
With regard to claim 2, Wasserstrom teaches a method of claim 1, wherein the second plurality of amplicons contain short tandem repeats (p 3-4 where the short tandem repeat loci are described).
With regard to claim 9, Wasserstrom teaches a method of claim 1, further comprising: removing amplicons having a length that is outside a first predetermined range from the first plurality of amplicons, prior to sequencing; and
removing amplicons having a length that is outside a second predetermined range from the second plurality of amplicons, prior to sequencing (Table 1, where the size range is between 66 and 149 bp).
With regard to claim 10, Wasserstrom teaches a method of claim 9, wherein the first predetermined range is 50 to 150 base pairs (Table 1, where the size range is between 66 and 149 bp).
With regard to claim 11, Wasserstrom teaches a method of claim 10, wherein the second predetermined range is 100 to 300 base pairs (Table 1, where the size range is between 66 and 149 bp).
With regard to claim 19, Wasserstrom teaches a method of claim 1, wherein identifying the trait associated with the DNA sample determining whether the DNA sample was derived from blood, skin, saliva, or semen (Example 7, where semen is tested).
With regard to claim 20, Wasserstrom teaches a method of claim 1, wherein identifying the trait associated with the DNA sample comprises identifying at least one of a cell type from which the DNA sample was derived, an age of an organism from which the DNA sample was derived, a disease state of an organism from which the DNA sample was derived, a risk of disease of an organism from which the DNA sample was derived, a response to environmental signals of an organism from which the DNA sample was derived, an expression level of one or more genes in an organism from which the DNA sample was derived, a physical characteristic of an organism from which the DNA sample was derived, a drug response of an organism from which the DNA sample was derived, an epigenetic inheritance of an organism from which the DNA sample was derived, or whether the DNA sample was synthesized in vitro (Example 4, where tissue source is identified and Example 7, where semen is tested and Example 4-6, where samples are characterized for multiple different features).
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 Deciu to include many specific method steps taught or suggested by Wasserstrom with a reasonable expectation for success. Wasserstrom teaches technology that “enables performing the categorization of DNA together with DNA profiling in the same reaction, thereby allowing for concomitant categorization and determination of identity of the samples” (p. 1 under “Summary of Invention”. Wasserstrom also teaches “describes methods for accurate and cost-effective categorization of DNA samples into different types of in vitro generated DNA or different types of natural DNA such as from different tissues and/or physiological/pathological states. The invention achieves categorization by comparing "signal ratios" that are correlated to ratios of methylation levels at specific genomic loci” (Abstract). Therefore, one of ordinary skill in the art at the time the invention was made would have adjusted the teachings of Deciu to include many specific method steps taught or suggested by Wasserstrom 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.
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/STEPHANIE K MUMMERT/Primary Examiner, Art Unit 1681
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