DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 04/23/2026 has been entered.
Applicant's amendments and remarks, 04/23/2026, are acknowledged. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Status of Claims
Claims 13-29 are under examination. Claims 1-12 are withdrawn.
Priority
This application is a continuation of U.S. Patent Application Serial No. 17/499,284, filed October 12, 2021, which is a continuation of U.S. Patent Application Serial No. 16/691,480, filed November 21, 2019, which is a continuation of U.S. Patent Application Serial No. 14/554,715, filed November 26, 2014, which is a continuation of U.S. Patent Application Serial No. 13/164,499, filed June 20, 2011, which claims priority to U.S. Provisional Application Serial No. 61/356,501 filed June 18, 2010.
After careful consideration, neither the claims nor the specification of Provisional Application No. 61/356,501 provides support for the instantly claimed feature of “not a human X/Y sex chromosome pair”. At best, the ‘501 application merely provides support for a chromosome pair that is “not the pair of human chromosome 17”. For these reasons, applicants are not given benefit of priority to Provisional Application No. 61/356,501 and the effective priority date of the instant application is June 20, 2011.
Withdrawn Rejections
The rejection of claims 13-29 under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more is withdrawn in view of applicant’s amendments.
Claim rejections - 35 USC § 112, 2nd Paragraph
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
The following rejections are necessitated by amendment.
Claims 13-29 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention. Claims that depend directly or indirectly from claim(s) 13 are also rejected due to said dependency.
Claim 13 recites “and wherein the genomic DNA comprising a homozygous genotype comprises an indicator loss of heterozygosity (LOH) region, further wherein the indicator LOH region is longer than 1.5 megabases but shorter than the length of the whole chromosome containing the indicator LOH region.” It is unclear what positive process limitation is intended by the above “wherein” clause, which now suggests a step of determining an indicator LOH region without explicitly requiring such a step. Applicant is reminded that intended use recitations are not given patentable weight and claim scope is not limited by claim language that “suggests” but does not limit a claim to a particular structure. See MPEP 2111.04. Moreover, the artisan would recognize that genotyping DNA sequences alone is not sufficient for detecting or identifying LOH regions, i.e. they are distinct processes. Therefore, the claim is indefinite. Clarification is requested via amendment.
Claim 27 recites “The method of claim 13, wherein a total number of indicator LOH regions is less than a predetermined reference and the subject is determined as less likely to respond to a treatment regimen comprising a DNA damaging agent, an anthracycline, a topoisomerase I inhibitor, radiation, a PARP inhibitor, or a combination thereof compared to a subject wherein a total number of indicator LOH regions detected is more than the predetermined reference.” The above limitation is problematic for the following reasons. (1) It is unclear what limiting effect is intended by the above “wherein” clause, which suggests positive process limitations without explicitly reciting them (e.g. determining a total number of indicator LOH regions and comparing them with a reference, determining patient response to a treatment). Applicant is reminded that intended use recitations are not given patentable weight and claim scope is not limited by claim language that “suggests” but does not limit a claim to a particular structure. See MPEP 2111.04. Therefore, the claim is indefinite. Clarification is requested via amendment.
(2) Parent claim 13 only requires sequencing DNA and genotyping DNA. As such, the above “wherein” clause appears to be relying upon information that has not even been previously obtained (e.g. a total number of indicator LOH regions). As a result, the claim is also rejected under 35 USC 112(b) for missing essential matter (e.g. determining a total number of indicator LOH regions) since it fails to interrelate the essential elements of the claimed invention. See also MPEP 2172.01. Therefore, the claim is indefinite. Clarification is requested via amendment.
Claim 28 recites “The method of claim 13, wherein a total number of indicator LOH regions is less than a predetermined reference and the subject is determined as less likely to respond to a treatment regimen comprising a taxane agent, a growth factor or growth factor receptor inhibitor, an antimetabolite, or a combination thereof compared to a subject wherein a total number of indicator LOH regions is more than the predetermined reference.” The above limitation is problematic for the following reasons. (1) It is unclear what limiting effect is intended by the above “wherein” clause, which suggests positive process limitations without explicitly reciting them (e.g. determining a total number of indicator LOH regions and comparing them with a reference, determining the likelihood of a patient response to a treatment). Applicant is reminded that intended use recitations are not given patentable weight and claim scope is not limited by claim language that “suggests” but does not limit a claim to a particular structure. See MPEP 2111.04. Therefore, the claim is indefinite. Clarification is requested via amendment.
(2) The above “wherein” clause appears to be relying upon information that has not even been previously obtained (e.g. a total number of indicator LOH regions). As a result, the claim is also rejected under 35 USC 112(b) for missing essential matter (e.g. determining a total number of indicator LOH regions and comparing them with a reference) since it fails to interrelate the essential elements of the claimed invention. See also MPEP 2172.01. Therefore, the claim is indefinite. Clarification is requested via amendment.
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 of this title, 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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
The following rejections are necessitated by amendment.
Claims 13-26 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Fortina et al. (WO 2004/001016; Pub. Date: 31 December 2003) in view of Huggins et al. ( J. Hum Genet, 2008, 53: 983–990) and Nannya et al. (Cancer Res, 2005; 65; pp. 6071-79).
Fortina teaches a method for determining the presence or absence of at least one genetic alteration in a target nucleic acid for the diagnosis and management of malignant disease [Abstract, Ref. claim 1]. Regarding claim(s) 13, Fortina teaches a) providing a target nucleic acid from a patient sample, said target nucleic acid having a predetermined sequence in the normal population; and b) assessing said target nucleic acid for the extent of loss of heterozygosity relative to predetermined loci, increased loss of heterozygosity, being correlated with enhanced tumor invasiveness and metastasis [ref. claim 1], wherein said assessing is selected from the group consisting of restriction enzyme mapping, hybridization of allele specific probes, oligomer ligation, DNA sequencing, and quantitative PCR [ref. claims 1 and 3]. Fortina additionally teaches means for determining which SNPs are present or absent in a patient sample based on genotyping assays (e.g. PCR amplification product complementary to the SNP location, Affymetrix GenFlex™ chip, etc.) [ref. claim 6, pages 5, 14-16, and Figure 5], as well as determining genotypes as homozygous or heterozygous [pages 20-21], and genotyping over 1000 single nucleotide loci [page 28 and Figure 2]. Furthermore, one of ordinary skill in the art would recognize that LOH regions are necessarily shorter than the whole chromosome containing the LOH region. Fortina also teaches screening for various cancers including adenocarcinomas, breast cancer, colorectal cancer, leukemias, lymphomas, ovarian cancer, pancreatic cancer, prostate cancer and retinoblastoma [page 8, ¶5]. Therefore, Fortina teaches sequencing and genotyping genomic DNA obtained from a subject.
Fortina does not specifically teach loci that are not in a human X/Y sex chromosome pair. However, Fortina teaches their SNE-based assay methods can be used to assess different chromosomal regions [page 8, ¶4], which at least suggests non-sex chromosome (i.e. autosome) analysis.
Moreover, Huggins teaches genomic methods for estimating LOH using genotyping arrays. In particular, Huggins teaches analyzing the autosomes in samples of 95 normal controls and 14 acute lymphoblastic leukaemia patients; performing genomewide scans of LOH with the Affymetrix Human Mapping 100K Set; and identifying the tumour suppressor gene CDKN2A (which the artisan would recognize is on an autosome), whose deletion was validated by quantitative polymerase chain reaction in multiple patients [Abstract].
Alternatively, Nannya teaches obtaining tumor samples from normal and diseased human patients [p.6071, col. 1]; assaying samples using high-density autosomal SNP genotyping arrays [p.6072, col. 1]; using the Affymetrix GeneChip Mapping 100k, which provides coverage for the entire genome and clearly allows for genotyping of more than 1000 SNPs [p.6071, col. 2, p.6072, col. 1, and Figure 1]; detecting multiple LOH regions along chromosomes with lengths in the range of 2 to 10 megabases [p.6072, col. 2, Table 1, Figure 3], which broadly encompasses six or more LOH regions (as the claims are not limited to any specific chromosomes or chromosomal positions); determining mean log ratio for X chromosomes between males and females and autosomal SNPs (i.e. not human X/Y sex chromosomes); analyzing a plurality of chromosomes that are not chromosome 17 [Figure 3].
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Fortina by alternatively genotyping loci that are not in a human X/Y sex chromosome pair, as claimed, since such analysis of non-sex chromosomes (i.e. autosomes) was routine and conventional in the art as taught by Huggins and Nannya, and since Fortina suggests Fortina their methods can be predictably used to assess different chromosomal regions [page 8, ¶4], which at least suggests non-sex chromosome (i.e. autosome) analysis. The motivation would have been to create a more robust assay that accounts for inherited driver mutations in cancer.
Regarding dependent claim(s) 14-26, all the elements of these claims are instantly disclosed or made obvious by Fortina, Huggins, and Nannya. Regarding claim(s) 14-16, Nannya teaches LOH regions in the 2MB to 10MB range (Table 1). Regarding claim(s) 17-18, Fortina teaches both targeted sequencing (i.e. primers and probes) and DNA sequencing (i.e. untargeted), as set forth above. Regarding claim(s) 19-21, Fortina does not specifically teach whole exome sequencing or transcriptome sequencing. However, the examiner takes official notice that such limitations are well understood, routine, and conventional and that these limitations are obvious variants of whole genome sequencing (since WGS captures both protein-coding (exons) and non-coding regions such as introns and regulatory sequences). Regarding claim(s) 22-25, Fortina teaches LOH regions detected in paired samples on chromosomes 1 and 16 [page 25, Figures 12A and 12B]. Fortina does not specifically teach at least 10 or 21 pairs of chromosomes. However, the choice of chromsomes is nothing more than a design consideration that does not change the function of the claimed process steps, as claimed, and Applicant has not disclosed that this particular feature provides an advantage, is used for a particular purpose, or solves a stated problem. Moreover, Fortina at a minimum suggests this limitation by teaching the use of their method to analyze additional chromosomal regions [page 8, ¶4]. Regarding claim(s) 26, this limitation is not given patentable weight as imposes no limiting effect on the method as claimed (i.e. the claims do not require treating a patient). For these reasons, the instant claims do not recite any new element or new function or unpredictable result.
Cited Prior Art
The following prior art made of record and not relied upon is considered pertinent to applicant' s disclosure.
Robinson (Briefings in Bioinformatics, Volume 11, Issue 5, September 2010, Pages 524–534), which teaches the application of second-generation sequencing to cancer genomics, including whole genomic sequencing, exome sequencing, and transcriptome sequencing.
Double Patenting
The non-statutory 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. See 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); ln re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 C.F.R. 1.321 (c) may be used to overcome an actual or provisional rejection based on a non-statutory double patenting ground provided the conflicting application or patent is shown to be commonly owned with this application. See 37 C.F.R. 1.130(b). Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 C.F.R. 3.73(b). [See also MPEP 804.02].
The conclusion of obviousness-type double patenting is made in light of these factual determinations. Any obviousness-type double patenting rejection should make clear: (A) The differences between the inventions defined by the conflicting claims; and (B) The reasons why a person of ordinary skill in the art would conclude that the invention defined in the claim at issue is anticipated by, or would have been an obvious variation of the invention defined in a claim in the patent.
Claims 13-29 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 14-20 of US Application 17/499,284.
The differences between the inventions defined by the conflicting claims are as follows: Reference claim(s) 14 of the ‘284 application teaches all aspects of the instant claim 13 plus additional features and/or limitations. Therefore, instant claim(s) 13 is/are anticipated by the narrower claims (i.e. species anticipates the genus). Moreover, dependent reference claims 15-20 teach or suggest all aspects of instant claims 14-29. Therefore, the instantly rejected claims 13-29 are made obvious over the combination of reference dependent claims because it would have been obvious to combine all limitations taught in the reference claims. This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Response to Arguments
Applicant’s arguments have been fully considered but are not persuasive for the following reasons. In particular, applicant argues that the cited reference application fails to teach “sequencing genomic DNA”. In response, this argument is not persuasive as the cited ‘284 claims explicitly teach this limitation (see at least claim 1). Accordingly, this rejection is maintained as the claims have not been amended to overcome the rejection and no terminal disclaimer(s) in compliance with 37 C.F.R. 1.321 (c) has been filed to overcome this rejection, as required by 37 C.F.R. 1.130(b).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PABLO S WHALEY whose telephone number is (571)272-4425. The examiner can normally be reached between 1pm-9pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Anita Coope can be reached at 571-270-3614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/PABLO S WHALEY/Primary Examiner, Art Unit 3619
Prosecution Insights