DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Claims 1-19 filed on 05/31/2023 are pending and under examination.
Information Disclosure Statement
The listing of references in the specification, at pages 27-32, is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Rejections - 35 USC § 112
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.
Claims 1-19 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 1, the recitation of “conducting genetic screening of the cfDNA” in line 19 of the claim is unclear if “the cfDNA” is referring to “day 4 cfDNA” in line 10 of the claim or is referring to “day 5/6/7 cfDNA” in line 18 of the claim.
Regarding claim 6, the recitation of “human serum albumen (HAS)” in line 3 of the claim is unclear is (HAS) is referring to something other than human serum albumen or is the result of a typographical error and should read “human serum albumen (HSA)”.
Regarding claim 7, the recitation of “a visible inner cell muss” in lines 2 of the claim is unclear what a “muss” is or if this is the result of a typographical error as should read “ a visible inner cell mass”.
Regarding claim 8, the recitation of “the genetic screening of the cfDNA” in line 2 of the claim is unclear if “the cfDNA” is referring to “day 4 cfDNA” in line 10 of claim 1, from which claim 8 depends from, or is referring to “day 5/6/7 cfDNA” in line 18 of claim 1, from which claim 8 depends from.
Regarding claim 9, the claim contains the trademark/trade name Exo-SAP-IT. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe enzymatic treatment of cfDNA with Exo nuclease I and Shrimp Alkaline phosphatase and, accordingly, the identification/description is indefinite.
Regarding claim 10, the claim contains the trademark/trade names SurePlexTM kit, Qubit 3.0TM fluorimeter, and VeriSeqTM PGS. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe conditions of whole genome amplification (WGA) and next generation sequencing (NGS) and, accordingly, the identification/description is indefinite.
Regarding claim 11, the claim contains the trademark/trade name SurePlexTM kit. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe conditions of whole genome amplification (WGA) and, accordingly, the identification/description is indefinite.
Regarding claim 14, the claim contains the trademark/trade name NexteraXTTM dual index set A-D. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe conditions of preparation of a cfDNA library and, accordingly, the identification/description is indefinite.
Regarding claim 15, the claim contains the trademark/trade name NxClinicalTM software. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe conditions of copy number variation (CNV) analysis and, accordingly, the identification/description is indefinite.
Claims 2-5 & 16-19 are rejected due to their dependence on claim 1 and claims 12 & 13 are rejected due to their dependence on claim 10.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 2, 4, 7, 8, 10-13, & 16-19 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kuznyetsov (Kuznyetsov et al.; PLOS One, Vol. 13, pages 1-15, May 2018), as cited on the IDS dated 10/25/2023, as evidenced by Illumina I (Illumina SurePlex Summary Protocol, pages 1-13, September 2020).
Regarding claim 1, Kuznyetsov teaches a method for blastocyst stage non-invasive preimplantation genetic screening (NIPGS) for chromosomal aneuploidy comprising culturing fertilized oocytes from day 1 of fertilization, removing and washing off cumulus-corona radiata prior to intracytoplasmic sperm injection (ICSI) on day 1 to decrease likelihood of maternal contamination, culturing individually from day 1 to day 4 in Sage 1-Step medium (culture medium) with a serum protein supplement, conducting a laser-assisted biopsy on day 4 to release trophectoderm (TE) cells (embryonic cell free DNA), transferring washed fertilized oocytes on day 4 into fresh Global HP medium with HSA under oil until they reached a blastocyst stage on day 5 or 6 ( culturing until day 5 or day 6 to form an expanded blastocyst), performing a laser assisted trophectoderm biopsy on the expanded blastocyst performed in Global “total” w/HEPES and protein medium (exposing said expanded blastocyst to a laser pulse to extrude blastocoel fluid containing embryonic cfDNA in the fresh drop of culture medium to obtain day 5/6/7 cfDNA), and conducting whole genome amplification and next generation sequencing on the biopsied TE cells (cfDNA) (conducting genetic screening using whole genome amplification (WGA) prior to implantation of the embryo) (abstract objective lines 1-4; pg. 3 3rd full paragraph lines 1-4; pg. 3 4th full paragraph lines 1-7; pg. 3-4 paragraph bridging pg. 3 & 4 lines 1-13; pg. 4 1st full paragraph lines 1-9; pg. 4 3rd full paragraph lines 1-5; pg. 12 1st full paragraph lines 1-13; Fig. 1).
Regarding claim 2, Kuznyetsov teaches a method for blastocyst stage non-invasive preimplantation genetic screening (NIPGS) for chromosomal aneuploidy comprising whole chromosome copy number (WCN) analysis as an indicator of aneuploidy (abstract objective lines 1-4; pg. 4 4th full paragraph lines 8; Fig. 2).
Regarding claim 4, Kuznyetsov teaches culturing individually from day 1 to day 4 in Sage 1-Step medium (culture medium) with a serum protein supplement under oil in 25-μL droplets (under oil in a culture medium droplet of about 25 μL) (pg. 3 3rd full paragraph lines 1-4).
Regarding claim 7, Kuznyetsov teaches performing a laser assisted trophectoderm biopsy on the expanded blastocyst at day 5 or day 6 when a visible inner cell mass is illustrated (pg. 4 1st full paragraph lines 1-9; pg. 11 4th full paragraph lines 3-5; pg. 12 1st full paragraph lines 4-6; Fig. 1).
Regarding claim 8, Kuznyetsov teaches analysis of the samples with WGA in samples with combined blastocyst culture conditioned medium (BCCM) (spent culture media) and blastocoel fluid (BF) (genetic screening on the cfDNA is assessed in both the spent culture media and the blastocoel fluid) (pg. 4 2nd full paragraph lines 1-3).
Regarding claim 10, Kuznyetsov teaches the WGA is conducted on cfDNA from all samples amplified using SurePlexTM kit as quantified by Qubit 3.0TM fluorimeter and then assessed by next generation sequencing (NGS) with VeriSeqTM PGS kit (pg. 4 3rd full paragraph lines 1-5).
Regarding claim 11, Kuznyetsov teaches the WGA is conducted on cfDNA from all samples amplified using SurePlexTM kit in which the SurePlexTM kit teaches pre-amplification for a total of 14 cycles (SurePlexTM kit employs 14 pre-amplification cycles for preparation of a library of sequences), as evidenced by Illumina I (pg. 9 Table 9 of Illumina I) (pg. 4 3rd full paragraph lines 1-5).
Regarding claims 12 & 13, Kuznyetsov teaches use of fluorescently labelled short tandem repeat (STR) marker for analysis of embryonic cfDNA (DNA resulting from WGA is subjected to PCR amplification followed by STR analysis wherein fluorescent markers are used) (pg. 4 3rd full paragraph lines 1-5; pg. 11 1st full paragraph lines 7-9).
Regarding claim 16, Kuznyetsov teaches the use of genetic screening through WGA for aneuploidy screening for use as a non-invasive preimplantation genetic screening (NIPGS) approach for human IVF before implantation into a human subject (step of implantation of the embryo if it satisfies the requirement of the genetic screening into a human subject (abstract conclusions lines 1-4).
Regarding claim 17, Kuznyetsov teaches the embryo may be frozen prior to implantation into a human subject from WGA for aneuploidy screening for use as a non-invasive preimplantation genetic screening (NIPGS) approach for human IVF (freezing the embryo that satisfies the requirement of the genetic screening prior to implanting in a human subject) (abstract conclusions lines 1-4; pg. 4 2nd full paragraph lines 1-3).
Regarding claim 18, Kuznyetsov teaches the use of genetic screening through WGA for aneuploidy screening for use as a non-invasive preimplantation genetic screening (NIPGS) approach for human IVF before implantation into a human subject (step of implantation of the embryo if aneuploidy is not indicated in the genetic screening into a human subject (abstract conclusions lines 1-4).
Regarding claim 19, Kuznyetsov teaches the embryo may be frozen prior to implantation into a human subject from WGA for aneuploidy screening for use as a non-invasive preimplantation genetic screening (NIPGS) approach for human IVF (freezing the embryo if aneuploidy is not indicated prior to implanting in a human subject) (abstract conclusions lines 1-4; pg. 4 2nd full paragraph lines 1-3).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 3, 5, & 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kuznyetsov (Kuznyetsov et al.; PLOS One, Vol. 13, pages 1-15, May 2018), as cited on the IDS dated 10/25/2023, in view of Gynmed (GynMed; GM501 Hyaluronidase protocol, pages 1-2, March 2017).
The teachings of Kuznyetsov with respect to claim 1 are discussed above and incorporated herein.
Regarding claims 3 & 5, Kuznyetsov teaches removing and washing off cumulus-corona radiata prior to intracytoplasmic sperm injection (ICSI) on day 1 to decrease likelihood of maternal contamination (see claim 3) and washing and replacing culture medium on day 4 to remove residual cumulus cells (see claim 5) (pg. 12 1st full paragraph lines 1-13).
Kuznyetsov does not teach that the washing comprises three washes to remove residual cumulus/corona cells.
Gynmed teaches a method of removing corona/cumulus cells with hyaluronidase comprising 3-5 washing steps (instructions for use lines 7, 8, & 13-16). Gynmed also teaches that this method enables washing steps to fully denude the oocyte for use in IVF (intended use lines 1-10; instructions for use lines 13-16).
Kuznyetsov and Gynmed are considered to be analogous to the claimed invention because they are all in the same field of removal of corona/cumulus cells from oocyte. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method washing off the cumulus-corona radiata at day 1 and at day 4 with fresh culture media to decrease likelihood of maternal contamination in Kuznyetsov to incorporate the use of three washing steps as taught in Gynmed because Gynmed teaches that doing so would enable full removal of the cumulus/corona cells from the oocyte of interest.
Regarding claim 6, Kuznyetsov teaches that each embryo was transferred on day 4 of culture, after washing and replacing to remove residual cumulus/corona cells, to Global HP medium with HSA in 24-μL droplets cultured under oil (fertilized oocyte is transferred to a fresh culture medium comprising Global HP medium with HSA under oil in a culture medium droplet of about 15 μL after washing to remove residual cumulus/corona cells) (pg. 3-4 paragraph bridging pg. 3 & 4 lines 1-3’ pg. 4 1st full paragraph lines 4-6).
Claim(s) 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kuznyetsov (Kuznyetsov et al.; PLOS One, Vol. 13, pages 1-15, May 2018), as cited on the IDS dated 10/25/2023, in view of ThermoFisher Scientific (ThermoFisher Scientific; Use of ExoSAP-IT PCR Product Cleanup Reagent in NGS, 2020).
The teachings of Kuznyetsov with respect to claims 1 & 2 are discussed above and incorporated herein.
Regarding claim 9, Kuznyetsov does not teach enzymatically treating the cfDNA with Exo nuclease I and Shrimp Alkaline phosphatase.
ThermoFisher Scientific teaches the use of ExoSAP-IT a PCR product cleanup reagent that is use in the library preparation for next generation sequencing (NGS) through removal of single-stranded DNA (cfDNA is enzymatically treated with Exo nuclease I and Shrimp Alkaline phosphatase (Exo-SAP-IT) to remove single stranded DNA prior to WGA) and that this product enables conservation of limited samples and improved workflow efficiency NGS for genotyping, targeted sequencing, etc. (pg. 1 column 1 1st full paragraph lines 1-15; pg. 1 column 1 2nd full paragraph lines 1-8; pg. 3 column 1 2nd full paragraph lines 1-4; Figure 1).
Kuznyetsov and ThermoFisher Scientific are considered to be analogous to the claimed invention because they are all in the same field of library preparation for NGS. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method preparing the samples for NGS in Kuznyetsov to incorporate the use of ExoSAP-IT as taught in ThermoFisher Scientific because ThermoFisher Scientific teaches that doing so would enable removal of single-stranded DNA and PCR product cleanup for library preparation prior to NGS while improving workflow efficiency.
Claim(s) 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kuznyetsov (Kuznyetsov et al.; PLOS One, Vol. 13, pages 1-15, May 2018), as cited on the IDS dated 10/25/2023, in view of Bronner (Bronner & Quail; Current Protocols in Human Genetics, Vol. 102, pages 1-48, 2019), as evidenced by Illumina II (Illumina Nextera XT DNA Library Prep Kit, pages 1-30, February 2018).
The teachings of Kuznyetsov with respect to claim 1 are discussed above and incorporated herein.
Regarding claim 14, Kuznyetsov teaches the use of NGS as the approach for preimplantation genetic screening (NIPGS) using the Illumina Veriseq PGS kit (pg. 10 3rd full paragraph lines 2-3).
Kuznyetsov does not teach the use of NexteraXTTM index for the preparation of a cfDNA library.
Bronner teaches the best practices for Illumina library preparation and the use of the Nextera XT kit when preparing libraries (WGA employs preparation of cfDNA library use NexteraXTTM set in which the Nextera XT kit employs 16 total amplification cycles as evidenced by Illumina II (pg. 7 step 2 of Illumina 2) (with 16 amplification cycles) (pg. 31 4th full paragraph lines 1-9). Bronner also teaches that the Nextera XT kit is quick and efficient method for preparing a DNA library and can allow for sequencing to be performed with low input DNA amounts (pg. 31 4th full paragraph lines 1-9).
Kuznyetsov and Bronner are considered to be analogous to the claimed invention because they are all in the same field of library preparation for NGS with Illumina. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method preparing the samples for library preparation for NGS in Kuznyetsov to incorporate the use of NexteraXTTM with 16 amplification cycles as taught in Bronner because Bronner teaches that doing so would provide a quick and efficient method to prepare a DNA library and sequence samples with low input DNA amounts.
Claim(s) 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kuznyetsov (Kuznyetsov et al.; PLOS One, Vol. 13, pages 1-15, May 2018), as cited on the IDS dated 10/25/2023, in view of Vossaert (Vossaert et al.; The American Journal of Human Genetics, Vol. 105, pages 1262-1273, December 2019).
The teachings of Kuznyetsov with respect to claims 1 & 2 are discussed above and incorporated herein.
Regarding claim 15, Kuznyetsov teaches data analysis and visualization of the WGA samples were done using BlueFuse Multi Software (pg. 3 4th full paragraph lines 5-7).
Kuznyetsov does not teach analyzing copy number variation analysis with NxClinicalTM software.
Vossaert teaches a methos of detecting aneuploidies and copy number variants for genetic analysis of samples for prenatal diagnosis through analysis of the samples with NxClinical software to analyze the copy number variants (CNVs) compared to reference for genome-wide CNV analysis (abstract lines 1-5; pg. 1264-1265 paragraph bridging pg. 1264 & 1265 lines 1-8; pg. 1265 column 1 1st full paragraph lines 1-7). Vossaert also teaches that the NxClinical software enables multiple modes of data visualization and multi-sample views of copy-number changes automatically called within the software.
Kuznyetsov and Vossaert are considered to be analogous to the claimed invention because they are all in the same field of analysis of samples for genetic screening for prenatal diagnosis of aneuploidy. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method analyzing the samples using BlueFuse Multi Software in Kuznyetsov to incorporate the use of NxClinicalTM software for CNV analysis as taught in Vossaert because Vossaert teaches that doing so would provide multiple modes of data visualization and multi-sample views of copy-number changes automatically called within the software.
Conclusion
Claims 1-19 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BAILEY C BUCHANAN whose telephone number is (703)756-1315. The examiner can normally be reached Monday-Friday 8:00am-5:00pm ET.
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/BAILEY BUCHANAN/Examiner, Art Unit 1682
/JEHANNE S SITTON/Primary Examiner, Art Unit 1682
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