DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 December 4, 2025 has been entered. Applicant’s remarks and amendments have been fully and carefully considered but are not found to be sufficient to put the application in condition for allowance. Any rejections or objections not reiterated herein have been withdrawn.
Claims 37-64 are currently pending and have been examined herein.
Claim Rejections - 35 USC § 101
3. 35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 37-64 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception without significantly more. The claims have been evaluated using the 2019 Revised Patent Subject Matter Eligibility Guidance (see Federal Register Vol. 84, No. 4 Monday, January 7, 2019).
Step 1: The claims are directed to the statutory category of a process.
Step 2A, prong one: Evaluate Whether the Claim Recites a Judicial Exception
The instant claims recite abstract ideas.
Claim 37 recites the following limitation:
A method for detecting a loss of heterozygosity (LOH) region, a telomeric allelic imbalance (TAI) region, and atransition (LST) region in genomic DNA of a cancer cell from a sample from a cancer patient that is a candidate for chemotherapy,
Claim 51 recites the following limitation:
(c) detecting, based on the genotype of the at least 10,000 loci, (i) an indicator loss of heterozygosity (LOH) region that is longer than 1.5 megabases but shorter than the length of the whole chromosome containing the LOH region, (ii) an indicator telomeric allelic imbalance (TAI) region that exhibits allelic imbalance, extends to one of the subtelomeres, and is longer than 1.5 megabases, and (iii) an indicator large scale transition (LST) region that is a somatic copy number breakpoint along the length of the whole chromosome that is between two regions of at least 6 megabases in length.
Claim 37 recites that the method is for detecting LOH, TAI, and LST (see preamble). The claim is considered to encompass “detecting”, even if this step is not recited in the active tense.
The broadest reasonable interpretation of the “detecting” in claim 37 and 51 is that it may be accomplished by a mental process. The “detecting” step encompasses the user of the method reading genotypes and thinking about whether the nucleic acid sequences meet the critera set forth in the claims for a LOH, TAI, and LST region. It is noted that the amount of base pairs that would need to be analyzed and the amount of time required to perform the analysis, is irrelevant for determining whether that procedure is a mental process: "the fact that the required calculations could be performed more efficiently via a computer does not materially alter the patent eligibility of the claimed subject matter. ... Using a computer to accelerate an ineligible mental process does not make that process patent-eligible" (Bancorp v. Sun Life, 103 USPQ2d 1425 at 1433-1434 (CAFC 2012)).
MPEP 2106.04(a)(2)(III)(A) states that claims recite a mental process when they contain limitations that can practically be performed in the human mind, including for example, observations, evaluations, judgments, and opinions. Examples of claims that recite mental processes include:
a claim to “collecting information, analyzing it, and displaying certain results of the collection and analysis,” where the data analysis steps are recited at a high level of generality such that they could practically be performed in the human mind, Electric Power Group v. Alstom, S.A., 830 F.3d 1350, 1353-54, 119 USPQ2d 1739, 1741-42 (Fed. Cir. 2016);
claims to “comparing BRCA sequences and determining the existence of alterations,” where the claims cover any way of comparing BRCA sequences such that the comparison steps can practically be performed in the human mind, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 763, 113 USPQ2d 1241, 1246 (Fed. Cir. 2014);
a claim to collecting and comparing known information (claim 1), which are steps that can be practically performed in the human mind, Classen Immunotherapies, Inc. v. Biogen IDEC, 659 F.3d 1057, 1067, 100 USPQ2d 1492, 1500 (Fed. Cir. 2011)
Step 2A, prong two: Evaluate Whether the Judicial Exception Is Integrated Into a Practical Application
The claims do NOT recite additional steps or elements that integrate the recited judicial exceptions into a practical application of the exception(s). For example, the claims do not practically apply the judicial exception by including one or more additional elements that the courts have stated integrate the exception into a practical application:
An additional element reflects an improvement in the functioning of a computer, or an improvement to other technology or technical field;
An additional element that applies or uses a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition;
An additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
An additional element effects a transformation or reduction of a particular article to a different state or thing; and
An additional element applies or uses the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological
environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception.
In addition to the judicial exception Claim 37 requires (a) genotyping a plurality of loci in the genomic DNA obtained from a cancer cell by contacting the genomic DNA with a single nucleotide polymorphism (SNP) array. In addition to the judicial exception claim 51 requires (a) sequencing genomic DNA obtained from a cancer cell from the cancer patient and (b) genotyping a plurality of loci. These steps are not considered to integrate the judicial exception into a practical application because they merely add insignificant extra-solution activity (data gathering) to the judicial exception.
Step 2B: Evaluate Whether the Claim Provides an Inventive Concept
In addition to the judicial exception Claim 37 requires (a) genotyping a plurality of loci in the genomic DNA obtained from a cancer cell by contacting the genomic DNA with a single nucleotide polymorphism (SNP) array. In addition to the judicial exception claim 51 requires (a) sequencing genomic DNA obtained from a cancer cell from the cancer patient and (b) genotyping a plurality of loci. These steps do not amount to significantly more because they simply append well understood, routine, and conventional activities previously known in the art, specified at a high level of generality, to the judicial exceptions.
In the instant case the teachings in the specification demonstrate the well understood, routine, conventional nature of additional elements because it teaches that the additional elements are well known or commercially available. For example the specification teaches the following:
[0105] As described herein, identifying CA loci (as well as the size and number of CA Regions) can include, first, determining the genotype of a sample at various genomic loci (e.g., SNP loci, individual bases in large-scale sequencing) and, second, determining whether the loci exhibit any of LOH, TAI or LST. Any appropriate technique can be used to determine genotypes at loci of interest within the genome of a cell. For example, single nucleotide polymorphism (SNP) arrays (e.g., human genome-wide SNP arrays), targeted sequencing of loci of interest (e.g., sequencing SNP loci and their surrounding sequences), and even large-scale sequencing (e.g., whole exome, transcriptome, or genome sequencing) can be used to identify loci as being homozygous or heterozygous. Typically, an analysis of the homozygous or heterozygous nature of loci over a length of a chromosome can be performed to determine the length of CA Regions. For example, a stretch of SNP locations that are spaced apart (e.g., spaced about 25 kb to about 100 kb apart) along a chromosome can be evaluated using SNP array results to determine not only the presence of a region of homozygosity (e.g., LOH) along a chromosome but also the length of that region. Results from a SNP array can be used to generate a graph that plots allele dosages along a chromosome. Allele dosage d, for SNP i can be calculated from adjusted signal intensities of two alleles (A.sub.i and B.sub.i): d.sub.i=A.sub.i/(A.sub.i+B.sub.i). An example of such a graph is presented in FIGS. 1 and 2, which show the difference between fresh frozen and FFPE samples and between SNP microarray and SNP sequencing analyses. Numerous variations on nucleic acid arrays useful in the invention are known in the art. These include the arrays used in the various examples below (e.g., Affymetrix 500K GeneChip array in Example 3; Affymetrix OncoScan™ FFPE Express 2.0 Services (Formerly MIP CN Services) in Example 4).
[0110] In some cases, targeted sequencing of known polymorphic loci (e.g., SNPs and surrounding sequences) can be done as an alternative to microarray analysis. For example, the genomic DNA can be enriched for those fragments containing a locus (e.g., SNP location) to be analyzed using kits designed for this purpose (e.g., Agilent SureSelect™, Illumina TruSeq Capture™, and Nimblegen SeqCap EZ Choice™). For example, genomic DNA containing the loci to be analyzed can be hybridized to biotinylated capture RNA fragments to form biotinylated RNA/genomic DNA complexes. Alternatively, DNA capture probes may be utilized resulting in the formation of biotinylated DNA/genomic DNA hybrids. Streptavidin coated magnetic beads and a magnetic force can be used to separate the biotinylated RNA/genomic DNA complexes from those genomic DNA fragments not present within a biotinylated RNA/genomic DNA complex. The obtained biotinylated RNA/genomic DNA complexes can be treated to remove the captured RNA from the magnetic beads, thereby leaving intact genomic DNA fragments containing a locus to be analyzed. These intact genomic DNA fragments containing the loci to be analyzed can be amplified using, for example, PCR techniques. The amplified genomic DNA fragments can be sequenced using a high-throughput sequencing technology or a next-generation sequencing technology such as Illumina HiSeq™, Illumina MiSeq™, Life Technologies SoLID™ or Ion Torrent™, or Roche 454™
Further it is noted that the courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity.
Determining the level of a biomarker in blood by any means, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017);
Using polymerase chain reaction to amplify and detect DNA, Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1377, 115 USPQ2d 1152, 1157 (Fed. Cir. 2015);
Detecting DNA or enzymes in a sample, Sequenom, 788 F.3d at 1377-78, 115 USPQ2d at 1157); Cleveland Clinic Foundation 859 F.3d at 1362, 123 USPQ2d at 1088 (Fed. Cir. 2017);
Immunizing a patient against a disease, Classen Immunotherapies, Inc. v. Biogen IDEC, 659 F.3d 1057, 1063, 100 USPQ2d 1492, 1497 (Fed. Cir. 2011);
Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs., 818 F.3d at 1377; 118 USPQ2d at 1546;
Freezing and thawing cells, Rapid Litig. Mgmt. 827 F.3d at 1051, 119 USPQ2d at 1375;
Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014)
For the reasons set forth above the claims are not directed to patent eligible subject matter.
Response To Arguments
4. In the response the Applicants traversed the rejection under 35 USC 101. The Applicants argue that claim 37 has been amended to remove recitation of “detecting” and instead recites characteristics of certain genotyped chromosomal aberration genomic loci. As such they argue that the claim does not recite a judical exception.
This argument has been fully considered but is not persuasive. Claim 37 recites that the method is for detecting LOH, TAI, and LST (see preamble). The claim is considered to encompass “detecting”, even if this step is not recited in the active tense. The broadest reasonable interpretation of the “detecting” steps is that it may be accomplished by a mental process. Thus claim 37 as amended is still considered to recite a judical exception.
Further the Applicants argue that claim 51 has been amended to recite, in part, “genotyping at least 10,000 loci...”. They argue that genotyping at least 10,000 loci is a process that cannot practically be performed in the human mind.
This argument has been fully considered. The rejection does not state that the genotyping step is a mental. Rather the rejection states that detecting step is a mental process. It is acknowledged that the detecting step is based on the genotype of at least 10,000 loci. However, the amount of base pairs that would need to be analyzed and the amount of time required to perform the analysis, is irrelevant for determining whether that procedure is a mental process: "the fact that the required calculations could be performed more efficiently via a computer does not materially alter the patent eligibility of the claimed subject matter. ... Using a computer to accelerate an ineligible mental process does not make that process patent-eligible" (Bancorp v. Sun Life, 103 USPQ2d 1425 at 1433-1434 (CAFC 2012)). The rejection is maintained.
Claim Rejections - 35 USC § 103
5. 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.
6. Claims 37-49 and 51-63 are rejected under 35 U.S.C. 103 as being unpatentable over Silver (WO 2013/0130347 Pub 9/6/2013 and Filed 2/22/2013 with priority to 61/602,460 Filed 2/23/2012 and 61,604,810 Filed 2/29/2012) in view of Popova (Cancer Research 72(21); 5454-5462 Nov. 1, 2012).
Regarding Claim 37 and 51 Silver teaches a method for predicting the outcome of anti-cancer treatment of a subject with a cell hyper proliferative disorder, comprising determining a global chromosomal aberration score (GCAS), comprising obtaining a biological sample from the subject and determining whether a plurality of chromosomal regions displaying a chromosomal aberration exists within a plurality of chromosomal loci, wherein said chromosomal aberrations are allelic imbalance (AI) and loss of heterozygosity (LOH) relative to a control, wherein the presence of a chromosomal regions displaying said chromosomal aberrations predicts the outcome of anti-cancer treatment of the subject (para 0007). Silver teaches that the biological sample comprises a cancer cell (para 0011). Silver defines a LOH region as a region of loss of heterozygosity that is longer than a first length but shorter than the length of the whole chromosome, wherein the first length is about 1.5 or more megabases (para 0029). Silver teaches that one type of AI that can be measured is telomeric imbalance. Silver defines a TAI region as a region of allelic imbalance that extends toward the telomere but does not cross the centromere, wherein the TAI region is 2 or more megabases (para 0081). Silver teaches that the GCAS is determined by adding together the number of individual chromosomal aberrations (para 0064). Silver teaches the anti-cancer therapy can be a DNA damaging agent, a anthracycline, a topoisomerase I inhibitor or a PARP inhibitor (para 0030). Silver teaches DNA arrays can be used to determine whether nucleic acid samples exhibit chromosomal aberrations (para 00171). Silver teaches the arrays comprise oligonucleotides corresponding to informative loci of interest including SNPs (para 00176). Silver further teaches that sequencing methods can be used for genotyping such as next generation sequencing (para 0079). Silver teaches the analysis of greater than 10,000 loci (para 0081). Thus Silver teaches a method for detecting LOH and TAI in genomic DNA of a cancer cell from a sample from a cancer patient that is a candidate for chemotherapy, comprising (a) genotyping a plurality of genomic loci in the genomic DNA obtained from a cancer cell by contacting the genomic DNA with a single nucleotide polymorphism (SNP) array OR (a) sequencing genomic DNA obtained from a cancer cell from the cancer patient and genotyping at least 10,000 loci and (b) detecting (i) a loss of heterozygosity (LOH) region that is longer than 1.5 megabases but shorter than the length of the whole chromosome containing the LOH region, and (ii) a telomeric allelic imbalance (TAI) region that exhibits allelic imbalance, extends to one of the subtelomeres, and is longer than 1.5 megabases.
Regarding Claims 38 and 52 Silver teaches a method wherein the cancer patient has a cancer selected from ovarian cancer, breast cancer, lung cancer, or esophageal cancer (para 00157).
Regarding Claims 39-40 and 53-54 Silver teaches a method wherein the anti-cancer treatment is a platinum based chemotherapy treatment (e.g., cisplatin, carboplatin) (para 0009). Thus Silver teaches a method wherein the chemotherapy for which the subject is a candidate is selected from a DNA damaging agent, wherein the DNA damaging agent is selected from cisplatin or carboplatin.
Regarding Claims 41-42 and 55-56 Silver teaches that where global chromosomal aberration score (GCAS) represents the total number of alterations present, subjects whose cancerous tissues exhibit a GCAS below a threshold value are predicted to have poorer response to therapy (e.g., radiation or chemotherapy) than those with high GCAS (above the threshold value) (para 00141). Thus Silver teaches a method wherein the subject does not respond to a treatment regimen comprising a DNA damaging agent (cisplatin or carboplatin) or radiation.
Regarding Claims 43-44 and 57-58 Silver teaches that the efficacy of anti-cancer therapies which damage DNA, as well as agents that take advantage of DNA repair defects but do not damage DNA themselves, as well as chemotherapy or radiation therapy is predicted according to the GCAS level of a cancer. Silver teaches that the chemotherapy can include antimetabolites such as methotrexate and 5-fluorouracil and taxanes such as paclitaxel and docetaxel (para 00149). Thus Silver teaches a method wherein the chemotherapy for which the subject is a candidate is selected from a taxane agent (paclitaxel or docetaxel) and an antimetabolite (5-fluorouracil or methotrexate).
Regarding Claims 45-46 and 59-60 Silver teaches that where global chromosomal aberration score (GCAS) represents the total number of alterations present, subjects whose cancerous tissues exhibit a GCAS below a threshold value are predicted to have poorer response to therapy (e.g., radiation or chemotherapy) than those with high GCAS (above the threshold value) (para 00141, 00137). Thus Silver teaches a method wherein the subject does not respond to a treatment regimen comprising a antimetabolites such as methotrexate and 5-fluorouracil and taxanes such as paclitaxel and docetaxel.
Regarding Claims 47-49 and 61-63 Silver teaches the analysis of at least two, five, ten, or 21 pairs of human chromosomes (see page 79, clm 34).
Silver does not teach detecting a LST region that is a somatic copy number breakpoint along the length of a whole chromosome that is between two regions of at least 6 megabases in length (clms 37 and 51).
However Popova teaches the detection of LST regions in basal-like breast carcinomas (BLC) (abstract). Popova defines a LST as a chromosomal break between adjacent regions of at least 10 MB, the number of LSTs in the tumor genome was estimated for each chromosome arm independently (not accounting for the centromeric breaks) and after filtering and smoothing of all variations less than 3 Mb (page 5457). Popova compared the number of LST regions detected in BRCA1 and non-BRCA1 basal like carcinomas (page 5456 right col to page 5457). Popova teaches that an elevated number of LSTs was strongly associated with a BRCA1 inactivated status in BLCs whereas all tumors with reduced number of LSTs showed no evidence of BRACA1 inactivation (page 5458, left col). Popova teaches that a high number of LSTs is a marker of homologous recombination pathway deficiency and surrogate measure of genomic instability (page 5460, left col). Popova further teaches that the efficiency of PARP inhibitors on BRCA1/2 mutated breast cancers and the correlation of response to platinum salts with BRCA1 status strongly supports the need to more accurately stratify sporadic BLC according to actual BRCAness which could easily be obtained using LST detection (page 5460).
Accordingly, it would have been obvious to one of ordinary skill in the art at the time the invention was made to have modified the method of Silver by further considering the number of LST regions and including the number of LST regions in the overall number of chromosomal aberrations as suggested by Popova. In the instant case Silver teaches that the presence of a plurality of chromosomal regions displaying chromosomal aberrations predicts the outcome of anti-cancer treatment of a subject (para 0002). Silver teaches that the summation of individual chromosomal aberrations can predict responsiveness of a cancer in a subject to anti-cancer agents independently of identifying specific chromosomal aberrations (para 0064). Popova teaches that LST, defined as a chromosomal break between adjacent regions of at least 10 Mb, is an additional type of chromosomal aberration. Popova teaches that an elevated number of LSTs was strongly associated with a BRCA1 inactivated status in BLCs whereas all tumors with reduced number of LSTs showed no evidence of BRACA1 inactivation (page 5458, left col). Popova further teaches that the efficiency of PARP inhibitors on BRCA1/2 mutated breast cancers and the correlation of response to platinum salts with BRCA1 status strongly supports the need to more accurately stratify sporadic BLC according to actual BRCAness which could easily be obtained using LST detection (page 5460). Thus it would have been obvious to an ordinary artisan to have further considered the number of Indicator LST regions and included the number of Indicator LST regions in the overall number of chromosomal aberrations when deciding how to treat a cancer patient for the benefit of including an additional type of chromosomal aberration that is predictive of the outcome of anti-cancer treatment of a patient.
7. Claims 50 and 64 are rejected under 35 U.S.C. 103 as being unpatentable over Silver (WO 2013/0130347 Pub 9/6/2013 and Filed 2/22/2013 with priority to 61/602,460 Filed 2/23/2012 and 61,604,810 Filed 2/29/2012) in view of Popova (Cancer Research 72(21); 5454-5462 Nov. 1, 2012) as applied to claims 37 and 51 above and in further view of Abkevich (British Journal of Cancer (10/9/2012) 107, 1776-1782).
The teachings of Silver and Popova are presented above.
The combined references do not teach a method wherein the LOH, TAI, and/or LST regions are not detected on human chromosome 17.
However Abkevich examined whether patterns of genomic loss of heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer. Abkevich teaches that the first cohort of samples was used as the ‘discovery’ cohort. LOH regions on chromosome 17 were excluded from the analysis, because LOH was observed over this chromosome in almost all samples. We checked for correlation between HR deficiency and the number of short LOH regions (o15 Mb), the number of long LOH regions (415 Mb but less than the whole chromosome), and the number of LOH regions covering whole chromosomes. The value of 15 Mb was selected somewhat arbitrarily, but further analysis showed that the exact value of this cut-off does not have significant impact on the results (Supplementary Figure S4). There was no significant correlation between the number of short LOH regions and HR deficiency. The number of LOH regions covering the whole chromosome was significantly greater in tumors with intact BRCA1 or BRCA2 (P¼ 4 10 5 ) (Supplementary Figure S3a). The number of long LOH regions (415 Mb but less than the whole chromosome) was significantly higher in tumors with deficient BRCA1 or BRCA2 (P¼ 10 11) (Figure 2A). From these samples, we determined a homologous recombination deficiency (HRD) score defined as the number of LOH regions 415 Mb, but less than a whole chromosome in length, within a tumor genome (page 1778, col 2).
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Silver and Popova by excluding chromosome 17 in their analysis of chromosomal aberrations. One of skill in the art would have been motivated to exclude chromosome 17 particularly since Abkevich that LOH regions on chromosome 17 were excluded from the analysis, because LOH was observed over this chromosome in almost all samples.
Response To Arguments
8. In the response the Applicants traversed the rejections under 35 USC 103. In the response the Applicants argue that they have met the burden of establishing unexpected reults because non only are the unexpected results described in the prior response of “statistical and practical significance” they are also “greater than those which would have been expected”. The Applicants rely on the post filing date art of Timms (Breast Cancer Research 2014 16:475). They argue that Timms teaches that LOH, TAI, and LST are signifincantly correlated with one another and this suggests that they all measure the same core genomic phenomenon (page 8, left column). This demonstrates one or ordinary skill in the art would have expected that using a combination of LOH, TAI, and LST would have been no better in measuring HRD than using any of the measures individually. They argue that Timms teaches that the scores could be combined resulting in stronger assoication with BRCA1/2 deficiency (page 8, left column). Further they argue that Timms concluded that “the most robust predictor of HRD deficicnecy is likely to be a combination of all three invidual HRD scores” (page 8, right column). Therefore, it is clear the claimed unexpected results are indeed unexpected and of statistical and practical significant.
This argument has been fully considered but is not persuasive. First it is noted that a showing of unexpected results must be commensurate in scope with the invention as claimed. Applicants are arguing that the combination of markers is better at measuring HRD, however HRD is not recited in the claims. The Examiner acknowledges that Timms teaches that markers are correlated with one another, however this statement does not demonstrate that it would be unexpected by one of ordinary skill in the art for the combination to work better. This is a mere opinion of what one of ordinary skill in the art would think. The examiner does not agree with this opinion. In the present situation the additive effect of using the combination of LOH, TAI, and LST (rather than anyone of LOH, TAI, and LST alone) is not be considered unexpected since each individual chromosomal aberration was known in the prior art to be associated with HRD. It is maintained that Applicants have not met the burden of establishing that the claimed unexpected property or result is actually unexpected and of statistical and practical significance.
Further Applicants argue that claims 51-64 are separately patentable. They argue that as amended the claims require “sequencing genomic DNA obtained from a cancer cell from the cancer patient” and “genotyping at least 10,000 loci associated with the indicator LOH regions, the indicator TAI regions, and the indicator LST regions in at least one pair of chromosomes”. They argue that neither Silver nor Popova teach or suggest detection of LST using a sequencing-based approach.
This argument has been fully considered but is not persuasive. Applicants are reminded that this is a 103 rejection and the prior art of Silver teaches sequencing genomic DNA and genotyping at least 10,000 loci to identify LOH regions and TAI regions. Silver does not teach detection of LST. However Popova teaches detection of LST. Popova is not required to teach sequencing because this is taught by Silver. The rejection suggests to modify the method of Silver by further detecting LST. The sequencing/genotyping data produced by Silver can be further analyzed to detect LST. The rejection is maintained.
Double Patenting
9. 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 §§ 706.02(l)(1) - 706.02(l)(3) 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.
10a. Claims 37-49 and 51-63 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 59 and 61-68 of US Application 17/353,279 in view of Silver (WO 2013/0130347 Pub 9/6/2013 and Filed 2/22/2013 with priority to 61/602,460 Filed 2/23/2012 and 61,604,810 Filed 2/29/2012). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding Claims 37 and 51 both sets of claims are drawn to a method for detecting a loss of heterozygosity (LOH) region, a telomeric allelic imbalance (TAI) region, and a large scale transition (LST) region in genomic DNA of a cancer cell from a sample from a cancer patient, comprising: (a) genotyping a plurality of CA genomic loci in the genomic DNA obtained from a cancer cell by contacting the genomic DNA with probes that hybridize to polymorphic regions and (b) detecting (i) a loss of heterozygosity (LOH) region that is longer than 1.5 megabases but shorter than the length of the whole chromosome containing the LOH region, (ii) a telomeric allelic imbalance (TAI) region that exhibits allelic imbalance, extends to one of the subtelomeres, and is longer than 1.5 megabases, and (iii) a large scale transition (LST) region that is a somatic copy number breakpoint along the length of the whole chromosome that is between two regions of at least 6 megabases in length (see claim 59 of the copending application). Regarding Claim 38 and 52 both sets of claims state that the cancer patient has a cancer selected from ovarian cancer, lung cancer, and esophageal cancer (see claim 59 of the copending claims). Regarding claims 47-49 and 61-63 both sets of claims encompass detecting the LOH, TAI, and/or LST regions in at least 2, 10, or 21 pairs of human chromosomes (see claim 67 of the copending application). The instant claims are different because they recite that the genotyping is done with a SNP array or sequencing assay (clm 37 and 51). However Silver teaches that DNA arrays can be used to determine whether nucleic acid samples exhibit chromosomal aberrations (para 00171). Silver teaches the arrays comprise oligonucleotides corresponding to informative loci of interest including SNPs (para 00176). Silver further teaches that sequencing methods can be used for genotyping such as next generation sequencing (para 0079). Accordingly, it would have been obvious to have modified the method of the patent by performing genotyping using a microarray or sequencing since this was conventional in the art as demonstrated by Silver. Additionally the instant claims are different because that a subject is less likely to respond to a treatment regimen comprising a DNA damaging agent, an anthracycline, a topoisomerase inhibitor, radiation, PARP inhibitor, taxane agent, growth factor or growth factor receptor inhibitor, or an antimetabolite when the total number of chromosomal aberration regions is less than a reference. However Silver teaches that where global chromosomal aberration score (GCAS) represents the total number of alterations present, subjects whose cancerous tissues exhibit a GCAS below a threshold value are predicted to have poorer response to therapy (e.g., radiation or chemotherapy) than those with high GCAS (above the threshold value) (para 00141). Further Silver provides a list of chemotherapies which includes those being claimed (para 00149). Accordingly, it would have been obvious to have modified the method of the patent by using the amount of detected chromosomal aberrations to predict response to treatment with the claimed therapies since this well known in the art as demonstrated by Silver.
10b. Claims 50 and 64 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 59 and 61-68 of US Application 17/353,279 in view of Silver (WO 2013/0130347 Pub 9/6/2013 and Filed 2/22/2013 with priority to 61/602,460 Filed 2/23/2012 and 61,604,810 Filed 2/29/2012) as applied to claims 37 and 51 above and in further view of Abkevich (British Journal of Cancer (10/9/2012) 107, 1776-1782). Although the claims at issue are not identical, they are not patentably distinct from each other.
The claims of the copending application are discussed above. The instant claims are different because the they recite a method wherein the LOH, TAI, and/or LST regions are not detected on human chromosome 17. However Abkevich examined whether patterns of genomic loss of heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer. Abkevich teaches that LOH regions on chromosome 17 were excluded from the analysis, because LOH was observed over this chromosome in almost all samples (page 1778, col 2).
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of the copending application in view of Silver by excluding chromosome 17 in their analysis of chromosomal aberrations. One of skill in the art would have been motivated to exclude chromosome 17 particularly since Abkevich that LOH regions on chromosome 17 were excluded from the analysis, because LOH was observed over this chromosome in almost all samples.
11a. Claims 37-49 and 51-63 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of US Patent 12,421,555 in view of Silver (WO 2013/0130347 Pub 9/6/2013 and Filed 2/22/2013 with priority to 61/602,460 Filed 2/23/2012 and 61,604,810 Filed 2/29/2012). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding Claims 37 and 51 both sets of claims are drawn to a method for detecting a loss of heterozygosity (LOH) region, a telomeric allelic imbalance (TAI) region, and a large scale transition (LST) region in genomic DNA of a cancer cell from a sample from a cancer patient, comprising: (a) genotyping a plurality of CA genomic loci in the genomic DNA obtained from a cancer cell by contacting the genomic DNA with probes that hybridize to polymorphic regions and (b) detecting (i) a loss of heterozygosity (LOH) region that is longer than 1.5 megabases but shorter than the length of the whole chromosome containing the LOH region, (ii) a telomeric allelic imbalance (TAI) region that exhibits allelic imbalance, extends to one of the subtelomeres, and is longer than 1.5 megabases, and (iii) a large scale transition (LST) region that is a somatic copy number breakpoint along the length of the whole chromosome that is between two regions of at least 6 megabases in length (see claim 1 of the patent). Regarding Claim 38 and 52 both sets of claims state that the cancer patient has a cancer selected from ovarian cancer, breast cancer, and esophageal cancer (see claim 3 of the patent). Regarding Claim 39 and 53 both sets of claims state that the therapy is selected from a DNA damaging agent, anthracycline, topoisomerase inhibitor, or PARP (see clm 1 of the patent). Regarding Claim 40 and 54 both sets of claims state that the therapy is cisplatin, carboplatin, oxalaplatin or picoplatin (see clm 5 of the patent). Regarding claims 47-49 and 61-63 both sets of claims encompass detecting the LOH, TAI, and/or LST regions in at least 2, 10, or 21 pairs of human chromosomes (see claim 2 of the patent). The instant claims are different because they recite that the genotyping is done with a SNP array or sequencing assay (clm 37 and 51). However Silver teaches that DNA arrays can be used to determine whether nucleic acid samples exhibit chromosomal aberrations (para 00171). Silver teaches the arrays comprise oligonucleotides corresponding to informative loci of interest including SNPs (para 00176). Silver further teaches that sequencing methods can be used for genotyping such as next generation sequencing (para 0079). Accordingly, it would have been obvious to have modified the method of the patent by performing genotyping using a microarray or sequencing since this was conventional in the art as demonstrated by Silver. Additionally the instant claims are different because that a subject is less likely to respond to a treatment regimen comprising a DNA damaging agent, an anthracycline, a topoisomerase inhibitor, radiation, PARP inhibitor, taxane agent, growth factor or growth factor receptor inhibitor, or an antimetabolite when the total number of chromosomal aberration regions is less than a reference. However Silver teaches that where global chromosomal aberration score (GCAS) represents the total number of alterations present, subjects whose cancerous tissues exhibit a GCAS below a threshold value are predicted to have poorer response to therapy (e.g., radiation or chemotherapy) than those with high GCAS (above the threshold value) (para 00141). Further Silver provides a list of chemotherapies which includes those being claimed (para 00149). Accordingly, it would have been obvious to have modified the method of the patent by using the amount of detected chromosomal aberrations to predict response to treatment with the claimed therapies since this well known in the art as demonstrated by Silver.
11b. Claims 50 and 64 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of US Patent 12,421,555 in view of Silver (WO 2013/0130347 Pub 9/6/2013 and Filed 2/22/2013 with priority to 61/602,460 Filed 2/23/2012 and 61,604,810 Filed 2/29/2012) as applied to claims 37 and 51 above and in further view of Abkevich (British Journal of Cancer (10/9/2012) 107, 1776-1782). Although the claims at issue are not identical, they are not patentably distinct from each other.
The claims of the copending application are discussed above. The instant claims are different because the they recite a method wherein the LOH, TAI, and/or LST regions are not detected on human chromosome 17. However Abkevich examined whether patterns of genomic loss of heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer. Abkevich teaches that LOH regions on chromosome 17 were excluded from the analysis, because LOH was observed over this chromosome in almost all samples (page 1778, col 2).
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of the copending application in view of Silver by excluding chromosome 17 in their analysis of chromosomal aberrations. One of skill in the art would have been motivated to exclude chromosome 17 particularly since Abkevich that LOH regions on chromosome 17 were excluded from the analysis, because LOH was observed over this chromosome in almost all samples.
12a. Claims 37-49 and 51-63 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of US Patent 10,400,287 in view of Silver (WO 2013/0130347 Pub 9/6/2013 and Filed 2/22/2013 with priority to 61/602,460 Filed 2/23/2012 and 61,604,810 Filed 2/29/2012). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding Claims 37 and 51 both sets of claims are drawn to a method for detecting a loss of heterozygosity (LOH) region, a telomeric allelic imbalance (TAI) region, and a large scale transition (LST) region in genomic DNA of a cancer cell from a sample from a cancer patient, comprising: (a) genotyping a plurality of CA genomic loci in the genomic DNA obtained from a cancer cell by contacting the genomic DNA with probes that hybridize to polymorphic regions and (b) detecting (i) a loss of heterozygosity (LOH) region that is longer than 1.5 megabases but shorter than the length of the whole chromosome containing the LOH region, (ii) a telomeric allelic imbalance (TAI) region that exhibits allelic imbalance, extends to one of the subtelomeres, and is longer than 1.5 megabases, and (iii) a large scale transition (LST) region that is a somatic copy number breakpoint along the length of the whole chromosome that is between two regions of at least 6 megabases in length (see claim 1 of the patent). Regarding Claim 39 and 53 both sets of claims state that the therapy is a DNA damaging agent (i.e., platinum agent) or PARP (see clm 1 of the patent). Regarding Claim 40 and 54 both sets of claims state that the therapy is cisplatin, carboplatin, oxalaplatin or picoplatin (see clm 3 of the patent). Regarding claims 47-49 and 61-63 both sets of claims encompass detecting the LOH, TAI, and/or LST regions in at least 2, 10, or 21 pairs of human chromosomes (see claim 1 of the patent). The instant claims are different because they recite that the genotyping is done with a SNP array or sequencing assay (clm 37 and 51). However Silver teaches that DNA arrays can be used to determine whether nucleic acid samples exhibit chromosomal aberrations (para 00171). Silver teaches the arrays comprise oligonucleotides corresponding to informative loci of interest including SNPs (para 00176). Silver further teaches that sequencing methods can be used for genotyping such as next generation sequencing (para 0079). Accordingly, it would have been obvious to have modified the method of the patent by performing genotyping using a microarray or sequencing since this was conventional in the art as demonstrated by Silver. Additionally the instant claims are different because that a subject is less likely to respond to a treatment regimen comprising a DNA damaging agent, an anthracycline, a topoisomerase inhibitor, radiation, PARP inhibitor, taxane agent, growth factor or growth factor receptor inhibitor, or an antimetabolite when the total number of chromosomal aberration regions is less than a reference. However Silver teaches that where global chromosomal aberration score (GCAS) represents the total number of alterations present, subjects whose cancerous tissues exhibit a GCAS below a threshold value are predicted to have poorer response to therapy (e.g., radiation or chemotherapy) than those with high GCAS (above the threshold value) (para 00141). Further Silver provides a list of chemotherapies which includes those being claimed (para 00149). Accordingly, it would have been obvious to have modified the method of the patent by using the amount of detected chromosomal aberrations to predict response to treatment with the claimed therapies since this well known in the art as demonstrated by Silver.
12b. Claims 50 and 64 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of US Patent 10,400,287 in view of Silver (WO 2013/0130347 Pub 9/6/2013 and Filed 2/22/2013 with priority to 61/602,460 Filed 2/23/2012 and 61,604,810 Filed 2/29/2012) as applied to claims 37 and 51 above and in further view of Abkevich (British Journal of Cancer (10/9/2012) 107, 1776-1782). Although the claims at issue are not identical, they are not patentably distinct from each other.
The claims of the patent are discussed above. The instant claims are different because the they recite a method wherein the LOH, TAI, and/or LST regions are not detected on human chromosome 17. However Abkevich examined whether patterns of genomic loss of heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer. Abkevich teaches that LOH regions on chromosome 17 were excluded from the analysis, because LOH was observed over this chromosome in almost all samples (page 1778, col 2).
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of the patent in view of Silver by excluding chromosome 17 in their analysis of chromosomal aberrations. One of skill in the art would have been motivated to exclude chromosome 17 particularly since Abkevich that LOH regions on chromosome 17 were excluded from the analysis, because LOH was observed over this chromosome in almost all samples.
13a. Claims 37-49 and 51-63 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of US Patent 12,221,656 in view of Silver (WO 2013/0130347 Pub 9/6/2013 and Filed 2/22/2013 with priority to 61/602,460 Filed 2/23/2012 and 61,604,810 Filed 2/29/2012). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding Claims 37 and 51 both sets of claims are drawn to a method for detecting a loss of heterozygosity (LOH) region and a large scale transition (LST) region in genomic DNA of a cancer cell from a sample from a cancer patient, comprising: (a) genotyping a plurality of CA genomic loci in the genomic DNA obtained from a cancer cell by contacting the genomic DNA with probes that hybridize to polymorphic regions and (b) detecting (i) a loss of heterozygosity (LOH) region that is longer than 1.5 megabases but shorter than the length of the whole chromosome containing the LOH region, and (ii) a large scale transition (LST) region that is a somatic copy number breakpoint along the length of the whole chromosome that is between two regions of at least 6 megabases in length (see claim 1 of the patent). Regarding Claim 38 and 52 both sets of claims state that the cancer patient has a cancer selected from ovarian cancer, breast cancer, and esophageal cancer (see claim 3 of the patent). Regarding Claim 39 and 53 both sets of claims state that the therapy is a DNA damaging agent (i.e., platinum agent) or PARP (see clm 1 of the patent). Regarding Claim 40 and 54 both sets of claims state that the therapy is cisplatin, carboplatin, oxalaplatin or picoplatin (see clm 5 of the patent). Regarding claims 47-49 and 61-63 both sets of claims encompass detecting the LOH, TAI, and/or LST regions in at least 2, 10, or 21 pairs of human chromosomes (see claim 2 of the patent). The instant claims are different because they recite that the genotyping is done with a SNP array or sequencing assay (clm 37 and 51). However Silver teaches that DNA arrays can be used to determine whether nucleic acid samples exhibit chromosomal aberrations (para 00171). Silver teaches the arrays comprise oligonucleotides corresponding to informative loci of interest including SNPs (para 00176). Silver further teaches that sequencing methods can be used for genotyping such as next generation sequencing (para 0079). Accordingly, it would have been obvious to have modified the method of the patent by performing genotyping using a microarray or sequencing since this was conventional in the art as demonstrated by Silver. Additionally the instant claims are different because that a subject is less likely to respond to a treatment regimen comprising a DNA damaging agent, an anthracycline, a topoisomerase inhibitor, radiation, PARP inhibitor, taxane agent, growth factor or growth factor receptor inhibitor, or an antimetabolite when the total number of chromosomal aberration regions is less than a reference. However Silver teaches that where global chromosomal aberration score (GCAS) represents the total number of alterations present, subjects whose cancerous tissues exhibit a GCAS below a threshold value are predicted to have poorer response to therapy (e.g., radiation or chemotherapy) than those with high GCAS (above the threshold value) (para 00141). Further Silver provides a list of chemotherapies which includes those being claimed (para 00149). Accordingly, it would have been obvious to have modified the method of the patent by using the amount of detected chromosomal aberrations to predict response to treatment with the claimed therapies since this well known in the art as demonstrated by Silver.
13b. Claims 50 and 64 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of US Patent 12,221,656 in view of Silver (WO 2013/0130347 Pub 9/6/2013 and Filed 2/22/2013 with priority to 61/602,460 Filed 2/23/2012 and 61,604,810 Filed 2/29/2012) as applied to claims 37 and 51 above and in further view of Abkevich (British Journal of Cancer (10/9/2012) 107, 1776-1782). Although the claims at issue are not identical, they are not patentably distinct from each other.
The claims of the patent are discussed above. The instant claims are different because the they recite a method wherein the LOH, TAI, and/or LST regions are not detected on human chromosome 17. However Abkevich examined whether patterns of genomic loss of heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer. Abkevich teaches that LOH regions on chromosome 17 were excluded from the analysis, because LOH was observed over this chromosome in almost all samples (page 1778, col 2).
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of the patent in view of Silver by excluding chromosome 17 in their analysis of chromosomal aberrations. One of skill in the art would have been motivated to exclude chromosome 17 particularly since Abkevich that LOH regions on chromosome 17 were excluded from the analysis, because LOH was observed over this chromosome in almost all samples.
14a. Claims 37-49 and 51-63 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 74-76, 78-80, 83-87, 91-92, and 95 of US Application 18/076,279 in view of Silver (WO 2013/0130347 Pub 9/6/2013 and Filed 2/22/2013 with priority to 61/602,460 Filed 2/23/2012 and 61,604,810 Filed 2/29/2012). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding Claims 37 and 51 both sets of claims are drawn to a method for detecting a loss of heterozygosity (LOH) region, a telomeric allelic imbalance (TAI) region, and a large scale transition (LST) region in genomic DNA of a cancer cell from a sample from a cancer patient, comprising: (a) genotyping a plurality of CA genomic loci in the genomic DNA obtained from a cancer cell by contacting the genomic DNA with probes that hybridize to polymorphic regions and (b) detecting (i) a loss of heterozygosity (LOH) region that is longer than 1.5 megabases but shorter than the length of the whole chromosome containing the LOH region, (ii) a telomeric allelic imbalance (TAI) region that exhibits allelic imbalance, extends to one of the subtelomeres, and is longer than 1.5 megabases, and (iii) a large scale transition (LST) region that is a somatic copy number breakpoint along the length of the whole chromosome that is between two regions of at least 6 megabases in length (see claims 74, 75, 78, 80, 86 of the copending application). Regarding Claim 38 and 52 both sets of claims state that the cancer patient has breast cancer (see claim 74 of the copending claims). Regarding Claim 39 and 53 both sets of claims state that the therapy is a DNA damaging agent (i.e., platinum agent) or PARP (see clm 91 of the copending application). Regarding Claim 40 and 54 both sets of claims state that the therapy is cisplatin, carboplatin, oxalaplatin or picoplatin (see clm 92 of the copending application). Regarding claims 47-49 and 61-63 both sets of claims encompass detecting the LOH, TAI, and/or LST regions in at least 2, 10, or 21 pairs of human chromosomes (see claim 84 of the copending application). The instant claims are different because they recite that the genotyping is done with a SNP array or sequencing assay (clm 37 and 51). However Silver teaches that DNA arrays can be used to determine whether nucleic acid samples exhibit chromosomal aberrations (para 00171). Silver teaches the arrays comprise oligonucleotides corresponding to informative loci of interest including SNPs (para 00176). Silver further teaches that sequencing methods can be used for genotyping such as next generation sequencing (para 0079). Accordingly, it would have been obvious to have modified the method of the copending application by performing genotyping using a microarray or sequencing since this was conventional in the art as demonstrated by Silver. Additionally the instant claims are different because that a subject is less likely to respond to a treatment regimen comprising a DNA damaging agent, an anthracycline, a topoisomerase inhibitor, radiation, PARP inhibitor, taxane agent, growth factor or growth factor receptor inhibitor, or an antimetabolite when the total number of chromosomal aberration regions is less than a reference. However Silver teaches that where global chromosomal aberration score (GCAS) represents the total number of alterations present, subjects whose cancerous tissues exhibit a GCAS below a threshold value are predicted to have poorer response to therapy (e.g., radiation or chemotherapy) than those with high GCAS (above the threshold value) (para 00141). Further Silver provides a list of chemotherapies which includes those being claimed (para 00149). Accordingly, it would have been obvious to have modified the method of the copending application by using the amount of detected chromosomal aberrations to predict response to treatment with the claimed therapies since this well known in the art as demonstrated by Silver.
14b. Claims 50 and 64 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 74-76, 78-80, 83-87, 91-92, and 95 of US Application 18/076,279 in view of Silver (WO 2013/0130347 Pub 9/6/2013 and Filed 2/22/2013 with priority to 61/602,460 Filed 2/23/2012 and 61,604,810 Filed 2/29/2012) as applied to claims 37 and 51 above and in further view of Abkevich (British Journal of Cancer (10/9/2012) 107, 1776-1782). Although the claims at issue are not identical, they are not patentably distinct from each other.
The claims of the copending application are discussed above. The instant claims are different because the they recite a method wherein the LOH, TAI, and/or LST regions are not detected on human chromosome 17. However Abkevich examined whether patterns of genomic loss of heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer. Abkevich teaches that LOH regions on chromosome 17 were excluded from the analysis, because LOH was observed over this chromosome in almost all samples (page 1778, col 2).
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of the copending application in view of Silver by excluding chromosome 17 in their analysis of chromosomal aberrations. One of skill in the art would have been motivated to exclude chromosome 17 particularly since Abkevich that LOH regions on chromosome 17 were excluded from the analysis, because LOH was observed over this chromosome in almost all samples.
Response To Arguments
15. In the response the Applicants traversed the double patenting rejections. The Applicants argue that all of the rejections rely on at least one secondary reference to provide elements that are present in the pending claims but absent from, the reference claims. As noted above in the arguments relating to Section 103, the claimed methods are significantly and unexpectedly better improved in detecting HRD compared to what one of ordinary skill in the art would have expected based on Silver and Abkevich. For at least these reasons and the reasons discussed above in the arguments relating to Section 103, Applicant respectfully requests that all of the rejections for alleged double patenting are reconsidered and withdrawn.
This argument has been fully considered but is not persuasive. It is noted for the record that each of the cited copending applications or patents require detecting the combination of LOH, TAI, and LST. Therefore the secondary references are not being relied upon to teach the recited combination and do not need to provide motivation to combine LST with LOH and TAI. The rejections are maintained.
16. Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMANDA HANEY whose telephone number is (571)272-8668. The examiner can normally be reached Monday-Friday, 8:15am-4:45pm EST.
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/AMANDA HANEY/Primary Examiner, Art Unit 1682