Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
This Office Action is in reply to Applicants’ correspondence of 11/24/2025.
Applicants’ remarks and amendments have been fully and carefully considered but are not found to be sufficient to put the application in condition for allowance. No new grounds of rejection are presented in this Office Action. Any rejections or objections not reiterated herein have been withdrawn in light of the amendments to the claims or as discussed in this Office Action.
This Action is made FINAL.
Please Note: The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Election/Restrictions
Claims 87 and 88 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as set forth on page 2 of the Office Action of 03/22/2023.
Maintained Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 77, 78 and 82 is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Mangia et al (2008).
Relevant to instantly rejected claim 77, Mangia et al teaches the detection of chromosomal alterations (i.e.: gains and losses of loci) in samples of breast cancer tissue (relevant to claim 82) who failed to show any abnormality in the BRCA1 and BRCA2 genes (i.e.: BRCAx) (p.76 – Patient enrollment; Tumor samples) of subjects. The reference teaches that the samples detected alterations in copy numbers (i.e.: gains and losses) that are at least 12 Mb in length, and extend to and involves a telomere but does not cross a centromere, including samples that demonstrate imbalances in at least two pairs of chromosomes (e.g: Table 1- Case 7, Area 1- Gain includes 8q13-qter and 9q21-qter).
Mangia et al provides an analysis of results obtained from comparative genomic hybridization, but does not explicitly teach detecting that comprises the use of molecular inversion probe (MIP), single nucleotide polymorphism (SNP) array, in situ hybridization, Southern blotting, transcriptional arrays, array comparative genomic hybridization (aCGH), or next-generation sequencing, as recited in claim 77.
However, such method for the detection of chromosomal gains and losses were known in the prior art, and in fact Mangi et al suggest the use of array comparative genomic hybridization (e.g.: Abstract- Further studies focusing on specific genes and sequences with more sensitive approaches, such as array-CGH, are warranted to confirm these findings).
It would have been prima facie obvious to someone with ordinary skill in the relevant art at the time the invention was made to have used any known prior art method of detecting chromosomal gains and losses, such as aCGH, in the detection of chromosomal alterations taught by Mangia et al. The skilled artisan would have been motivated to use aCGH based on the expressed teachings of Mangia et al that array-CGH may provide more information related to specific genes and sequences and provide a more sensitive assay. The use of array-CGH would be the simple substitution of one know technique for another with predictable results.
Response to Remarks
Applicants have traversed the rejection of claims as rendered obvious by the teachings of Mangia et al as maintained above. Applicants’ remarks (p.4-6 of the Remarks of 11/24/2025) have been considered but are not persuasive to withdraw the rejection). Applicants asserts that the prior art teaches a global analysis of chromosomal changes, and does teach the presence of alterations with the required structures (i.e.: at least 12Mb in length; includes the telomere; does not cross the centromere), the art does not expressly disclose “detecting a number” of those alterations. The argument is not persuasive because the prior art in fact teaches a listing of the alterations, including the alteration structures of the claims, which provides each of the alterations as a separate entry (e.g.: Table 1). Furthermore, the Supplementary data of the publication, provided as part of the online publication, includes the result of the analyses in ideograms that include each of the relevant alterations. As such the number of each alteration is implicitly disclosed. Applicants further argue that the methods as claimed have some particular advantage in the detection of homologous recombination deficiency based on the detection of 8 or more of the recited structures. This argument is not persuasive because there is nothing in the claims that requires performing an evaluation of the number of alterations to reach a conclusion about the presence of homologous recombination deficiency. Applicants appear to be arguing that the data collection of the claims, which is rendered obvious by the cited prior art, can be used in some mental evaluation of the data to reach a conclusion. And while such an abstract idea may be a part of some analysis conceived by the Applicants, this analysis is not part of the claims. Furthermore, where the claims recite “detecting … a number of telomeric allelic imbalances … as either (i) greater than or equal to eight or (ii) less than 8”, Applicants appear to argue that the claims are directed to a comparison of the data to some threshold value, or classification of samples based on the collected data. However, in the broadest reasonable interpretation of the claims, where the claim include detecting any value that is greater than 8, equal to 8, or less that 8, the claims are directed to detection alterations of any amount (where claim 77 recites “the telomeric allelic imbalances are detected in at least one pair of human chromosomes of the cancer cell”, the claim do not encompass the detection of zero of the recites imbalances).
Claims 79-81 and 85 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Mangia et al (2008) as applied to claim 77, 78 and 82 above, and further in view of Wasenius et al (1997) (cited on the IDS of 02/18/2025).
Mangia et al renders obvious the detection of alterations in copy numbers (i.e.: gains and losses) that are at least 12 Mb in length, and extend to and involve a telomere but does not cross a centromere, in samples of BRCAx breast cancers using aCGH methods.
Mangia et al does not exemplify the detection of alterations that are at least 12 Mb in length, and extend to and involve a telomere but does not cross a centromere, in at least 5, 10 or 21pairs of chromosomes (claims 79, 80 and 81), or at least 20 alterations (claim 85).
However, the detection of various alterations in cells associated with caner phenotype and pathology was known in the prior art and is taught by Wasenius et al. Wasenius et al teaches the detection of a variety of chromosomal losses and gains, including alteration that are at least 12 Mb in length, and extend to and involve a telomere but does not cross a centromere (e.g.: Figure 1) in cells resistance to different chemotherapeutic agents.
It would have been prima facie obvious to someone with ordinary skill in the relevant art at the time the invention was made to have used the methods of Mangia et al to detect different chromosomal gains and losses that that are at least 12 Mb in length, and extend to and involve a telomere but does not cross a centromere, including the numbers of alterations as required by the instantly rejected claims. Where Wasenius teaches that phenotypic patterns of resistance can be linked to specific genetic changes, the skilled artisan would understand that various different combinations of chromosomal alterations may be associated with specific phenotypes (such as different resistances to different therapeutics). Thus, it would be obvious to use the methods rendered obvious by Mangia et al to investigate any samples in the interest of finding alterations associated with specific phenotypes, where Wasenius et al suggests that the finding of different alterations, and different number of alterations is a results effective variable associated with cellular phenotype.
Claims 83 and 84 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Mangia et al (2008) as applied to claim 77, 78 and 82 above, and further in view of Li et al (2008) (cited on the IDS of 03/08/2022).
Mangia et al renders obvious the detection of alterations in copy numbers (i.e.: gains and losses) that are at least 12 Mb in length, and extend to and involve a telomere but does not cross a centromere, in samples of BRCAx breast cancers using aCGH methods.
Mangia et al does not exemplify the detection of alterations using major copy proportion (MCP) (claim 83), or a MCP that is greater than 0.70.
However, the detection of copy number alterations using MCP, and various levels of MCP is the determination of alterations, was known in the art and is taught by Li et al.
Li et al teaches methods that include using MCP analysis of oligonucleotide SNP array data to provide an accurate measure of gnomic structure in tumor cells. The teachings of Li et al include measures of MCP encompassing 0.70 to analyze genomic content (e.g.: p.6 - Comparing MCP and LOH).
It would have been prima facie obvious to someone with ordinary skill in the relevant art at the time the invention was made to have used any known prior art method of detecting chromosomal gains and losses, such as using MCP in the anlysis of SNP array data as taught by Li et al, in the detection of chromosomal alterations taught by Mangia et al. The skilled artisan would have been motivated to use measures of MCPbased on the expressed teachings of Li et al that such methods perform effectively in the detection of allelic imbalances (e.g.: p.13 – Conclusion). The use of MCP-based methods would be the simple substitution of one know technique for another with predictable results.
Claims 90 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Mangia et al (2008) as applied to claim 77, 78 and 82 above, and further in view of Medvedev et al (2009).
Mangia et al renders obvious the detection of alterations in copy numbers (i.e.: gains and losses) that are at least 12 Mb in length, and extend to and involve a telomere but does not cross a centromere, in samples of BRCAx breast cancers using aCGH methods.
Mangia et al does not exemplify the detection of alterations using next generation sequencing (NGS).
However, the detection of copy number alterations using NGS was known in the art and is reviewed by Medvedev et al.
It would have been prima facie obvious to someone with ordinary skill in the relevant art at the time the invention was made to have used any known prior art method of detecting chromosomal gains and losses, such as using NGS-based methods as taught by Medvedev et al, in the detection of chromosomal alterations taught by Mangia et al. The skilled artisan would have been motivated to use NGS based on the expressed teachings of Medvedev et al that such methods provide several advantages over other methods (e.g.: p.S18, right col). The use of NGS-based methods would be the simple substitution of one know technique for another with predictable results.
Maintained Claim Rejection – 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 77-85 and 90 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 9,512,485 in view of Mangia et al (2008).
The conflicting patent are directed to the analysis and detection of the same chromosomal aberrations as the instantly rejected claims (i.e.: 12 Mb and that extend to and involve the telomere and do not cross the centromere) in the same sample types (e.g.: breast cancer cells) using the same methodological techniques to detect chromosomal aberrations.
The conflicting claims do not specify a subject cancer cell that does not have pathological mutation of BRCA1 or BRCA2, but the analysis of chromosomal aberrations of such cell was known in the art and is taught by Mangia et al.
It would have been prima facie obvious to someone with ordinary skill in the relevant art at the time the invention was made to have applied the methods of the prior art to the cells of Mangia et al. The skilled artisan would have been motivated to analyze the cells of Mangia et al based on the expressed teachings of Mangia et al that analysis of tumor heterogeneity provides relevant information about cancer pathology.
Claims 77-85 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 10,190,160 in view of Mangia et al (2008).
Claim 90 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 10,190,160 in view of Mangia et al (2008) and further in view of Medvedev et al (2009)
The conflicting claims do not specify a subject cancer cell that does not have pathological mutation of BRCA1 or BRCA2, but the analysis of chromosomal aberrations of such cell was known in the art and is taught by Mangia et al.
It would have been prima facie obvious to someone with ordinary skill in the relevant art at the time the invention was made to have applied the methods of the prior art to the cells of Mangia et al. The skilled artisan would have been motivated to analyze the cells of Mangia et al based on the expressed teachings of Mangia et al that analysis of tumor heterogeneity provides relevant information about cancer pathology.
With regard to the rejection of claim 90, the teachings of Medvedev have been discussed previously in this Office Action, and are applied to the instant rejection as they were applied previously to render obvious the use of NGS in the detection of chromosomal alterations.
Claims 77-85 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 11,299,782 in view of Mangia et al (2008).
Claim 90 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 11,299,782in view of Mangia et al (2008) and further in view of Medvedev et al (2009)
The conflicting claims do not specify a subject cancer cell that does not have pathological mutation of BRCA1 or BRCA2, but the analysis of chromosomal aberrations of such cell was known in the art and is taught by Mangia et al.
It would have been prima facie obvious to someone with ordinary skill in the relevant art at the time the invention was made to have applied the methods of the prior art to the cells of Mangia et al. The skilled artisan would have been motivated to analyze the cells of Mangia et al based on the expressed teachings of Mangia et al that analysis of tumor heterogeneity provides relevant information about cancer pathology.
With regard to the rejection of claim 90, the teachings of Medvedev have been discussed previously in this Office Action, and are applied to the instant rejection as they were applied previously to render obvious the use of NGS in the detection of chromosomal alterations.
Response to Remarks
Applicants have traversed the rejections of claims for issues related to double patenting, as maintained above. Applicants’ arguments (p.6-7 of the Remarks of 11/24/2025) have been considered but are not persuasive to withdraw the rejections. Applicants have argued that the additional cited prior art of Magnia et al does not teach or suggest detecting a number telomeric allelic imbalances, as recited in the instantly rejected claims. This argument is not persuasive of the reasons set forth in the Response to Remarks provided previously in this Office Action; and furthermore it is noted that limitations related to detecting a number of telomeric allelic imbalances in a sample are provided by the conflicting claims cited in the rejections above.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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Stephen Kapushoc
Primary Examiner
Art Unit 1683
/STEPHEN T KAPUSHOC/Primary Examiner, Art Unit 1683