DETAILED ACTION
The present Office Action is responsive to the After-Final Amendment received on June 5, 2026.
Preliminary Remark
Claims 1, 3-6, 12, 17, 19-21, and 28-31 are canceled.
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.
Claims 2, 7, 9-11, 13-16, 18, 24, 26, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Huang et al. (Analytical and Bioanalytical Chemistry, 2019, vol. 411, pages 6825-6835) in view of Khamlor et al. (Theriogenology, 2015, vol. 83, pages 891-896) and Hromadnikova et al. (Prenatal Diagnosis, 2003, vol. 23, pages 235-238).
With regard to claims 2 and 24, Huang et al. teach a method comprising:
obtaining a biological sample from a subject who is pregnant or suspected of being pregnant comprising fetal nucleic acids, wherein the sample volume is less than 1 ml (“[s]amples were collected from patients … needle is inserted into the mother’s abdominal wall, through the wall, through the wall of uterus, until it reaches the umbilical cord … the umbilical cord is punctured away … In this study, 1 mL of cord blood was used to drop on filter paper for each patient”, page 6827, 1st column, 2nd paragraph);
performing amplification on one or more target fetal nucleic acids in the sample to generate a detectable product if the target nucleic acids are present in the sample (“[a] paper-dried blood sample was used for amplification in a 50 mL PCR mixture containing DDB buffer … filter dried paper cord blood was added (9 mm2 filter paper with 1mL of blood per 50 mL of PCR mixture) to the bottom of the PCR tube without any agitation,” page 6827, 1st column, bottom paragraph); and
detecting the amplification product (“PCR products were separated either through gel electrophoresis or microchip electrophoresis”, page 6827, 2nd column, 2nd paragraph).
With regard to claim 9, the target nucleic acid is PKU, PAH, IDS, COL1A2 gene (see page 6826, 2nd column, bottom paragraph to page 6827, 1st column, 1st paragraph).
With regard to claim 11, the sample is blood (see above).
With regard to claims 16 and 18, the sample is also added with anticoagulants (EDTA) (“[t]o evaluate the effect of an anticoagulant on the efficiency of direct PCB PCR, blood samples treated with different anticoagulant (dipotassium EDTA, sodium citrate, and heparin sodium) were used in PCB PCR”, page 6829, 2nd column, bottom paragraph t page 6830, 1st column).
Huang et al. do not teach that the amplification means is via isothermal amplification, wherein the detection of the amplified product is via reporter molecules, wherein the detection of the reporter is detected in less than 60 minutes (claim 13), or via means recited in claim 14, with isothermal amplification means recited in claim 15.
Huang et al. only assay for the presence of genetic disorder and therefore, do o teach that multicopy target sequence on Y-chromosome is assayed (claims 7 and 10).
Huang et al. do not teach that the detection results in at least 90% accuracy (claim 26), wherein the gestational age of fetus is between 4 weeks to 20 weeks (claim 27).
Khamlor et al. teach a well-known established isothermal amplification detection known as LAMP which employs a reporter to detect the presence of a target nucleic acid (“loop primer was labeled with 6-carboxyl-X-rhodamine (ROX), emitting red color under ultraviolet (UV) light, and both Sat1 loop primers were labeled with fluorescein isothiocyanate (FITC), exhibiting green color under UV light”, page 892, 1st column, “[o]range precipitate indicated a male specimen because both the male-specific primers (red) and the internal control primers (green) were used and incorporated into the amplified product … green precipitate indicated a female specimen because only the internal control primers were incorporated in the amplified product”, page 892, 2nd column).
The LAMP reaction was performed for 1 hours (or 60 minutes, see page 892, 2nd column).
The reaction was 100% accurate (“multiplex LAMP showed 100% accuracy in identifying actual sex of the embryos and provides a fast, simple, and cost-effective tool”, Abstract).
Hromadnikova et al. teach a well-established means of typing for baby’s sex via non-invasive means, wherein the sample is taken during 10-18 weeks of pregnancy (see page 235, 2nd column).
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 combine the teachings of Huang et al. with the teachings of Khamlor et al. and Hromadnikova et al., thereby arriving at the invention as claimed for the following reasons.
As discussed above, Huang et al. teach that a less than 1 mL of blood sample collected from a pregnant woman is directly utilized in a method of amplification. While Huang et al. did not employ all types of amplification known at the time the invention was made, one of ordinary skill in the art would have had a reasonable expectation that other known means of amplification would have yielded the same predicted outcome of amplifying the fetal nucleic acids present in the sample collected via method of Huang et al., that is amplifying nucleic acids via known means from a sample of the requisite size which has been demonstrated to by amplifiable, the amplification means such as LAMP reaction that produces results within 60 minutes (as demonstrated by Khamlor et al.).
As to utilizing the cord blood to identify other regions of the fetal DNA for identification of sex, targeting regions conventionally known to be targeted (as demonstrated by Hromadnikova et al.), would have also have expected to be successful given that Huang et al. teach that the artisans teach that their method successfully “determine fetal single-gene disorders and chromosomal diseases in all 46 chromosomes.” (see Abstract)
Therefore, the invention as claimed is deemed prima facie obvious over the cited references.
Rejection - Maintained
The rejection of claims 2, 7-11, 13-16, 18, and 22-27 under 35 U.S.C. 103 as being unpatentable over Horlitz et al. (WO 2013/045432 A1, published April 2013) in view of Khamlor et al. (Theriogenology, 2015, vol. 83, pages 891-896) and Hromadnikova et al. (Prenatal Diagnosis, 2003, vol. 23, pages 235-238), made in the Office Action mailed on April 16, 2026 is maintained for the reasons of record.
Applicants’ arguments presented in the Amendment received on June 5, 2026 have been carefully considered but they have not been found persuasive for the reasons discussed in the “Response to Arguments” section.
The Rejection:
With regard to claim 2, Horlitz et al. teach a well-known means of analyzing extracellular nucleic acids from variety of sample types and detecting such nucleic acids by a variety of analysis methods known in the art, with particular steps of:
obtaining a biological sample from a subject who is pregnant or suspect of being pregnant comprising fetal nucleic acids (see Prenatal Diagnostics, page 50, lines 11-14 “[c]irculating cell-free nucleic acid was isolated from maternal blood samples … 5.8 ml plasma was processed from twelve individual donors”);
performing isothermal amplification on one or more target fetal nucleic acids in the sample, if the target nucleic acids are present in the sample (“The isolated extracellular nucleic acids and/or a specific target extracellular nucleic acid comprised or suspected of being comprised therein can be identified, quantified, modified, contacted with at least one enzyme, amplified, reverse transcribed, …”, page 32, lines 26-28, also “the isolated extracellular nucleic acids are analyzed to identify and/or characterize a disease or a fetal characteristic … may further comprise a step c) of nucleic acid analysis and/or processing … analysis further processing of the nucleic acids can be performed using any nucleic acid analysis/processing method including, but not limited to amplification technologies, polymerase chain reaction (PCR), isothermal amplification … NASBA … HDA … ” (page 33, lines 5-8); and
detecting the target molecule wherein the detection indicates the presence of target fetal nucleic acids in the sample (“The isolated extracellular nucleic acids and/or a specific target extracellular nucleic acid comprised or suspected of being comprised therein can be identified, quantified, modified, contacted with at least one enzyme, amplified, reverse transcribed, …” (page 32, lines 26-28).
With regard to claim 7, the artisans disclose targeting DYS14 which is located on the Y-chromosome (“triplex qPCR assay for detection of 18S rDNA … DYS14 … and RhD …), wherein DSY14 a Y-chromosome marker and thus can be used as sex typing1.
With regard to claims 8 and 24, the target fetal nucleic acid is cell-free fetal DNA (“The term ‘extracellular nucleic acids’ or ‘extracellular nucleic acid2’ as used herein, in particular refers to nucleic acids …such as fetal DNA and/or RNA …”, page 10, line 33 to page 11, line 2).
With regard to claims 9 and 10, the target nucleic acid DSY14 (see above), which exist as a multi copy marker.
With regard to claim 11, the sample is blood or plasma (“method is provided for isolating extracellular nucleic acid from a sample which is or is derived from a body fluid, preferably from blood, plasma, serum, or urine”, page 6, lines 5-7).
With regard to claim 15, the detection is disclosed as being HDA or NASBA (“the isolated extracellular nucleic acids are analyzed to identify and/or characterize a disease or a fetal characteristic … may further comprise a step c) of nucleic acid analysis and/or processing … analysis further processing of the nucleic acids can be performed using any nucleic acid analysis/processing method including, but not limited to amplification technologies, polymerase chain reaction (PCR), isothermal amplification … NASBA … HDA … ”, page 33, lines 5-8).
With regard to claims 16 and 18, the sample is also pretreated with a preservative such as EDTA (“term ‘sample’ preferably refers to a natural sample, e.g., as obtained from a human or animal … optionally stabilized by appropriate agents … in particular samples that derive from a body fluid by removing cells from the body fluid … Blood is obtained from the human or animal and usually is immediately stabilized e.g., in EDTA or other suitable stabilization compositions (see above).”, page 27, lines 14-23).
With regard to claims 22 and 23, the sample is enriched for fetal nucleic acids (“it is also within the scope of the present invention to specifically isolate specific target extracellular nucleic acids from the enriched extracellular nucleic acid population, e.g., by using appropriate probes that enable a sequence specific binding and are coupled to a solid support”, page 33, lines 35-39).
With regard to claim 25, the artisans teach isolating, enriching and/or concentrating fetal nucleic acids (“method is provided for isolating extracellular nucleic acid from a sample which is or is derived from a body fluid, preferably from blood, plasma, serum, or urine”, page 6, lines 5-7; “binding the extracellular nucleic acids to the solid phase … separating the solid phase with the bound extracellular nucleic acids … washing the extracellular nucleic acids … eluting extracellular nucleic acids from the solid phase”, page 8, lines 28-34; “it is also within the scope of the present invention to specifically isolate specific target extracellular nucleic acids from the enriched extracellular nucleic acid population, e.g., by using appropriate probes that enable a sequence specific binding and are coupled to a solid support”, page 33, lines 35-39).
While Horlitz et al. explicitly teach that their method employs a variety of detection means for detecting the presence of the target cell-free fetal nucleic acid, including isothermal amplification means, the artisans do not explicitly teach all types of isothermal amplification means, nor that the isothermal amplification detection means employ a “reporter”, wherein the detection is achieved by the detection of the reporter.
Therefore, the artisans do not teach that the detection of the reporter is detected in less than 60 minutes (claim 13), has a 90% accuracy (claim 26), or that the sample volume is less than 1 ml (claim 28).
While Horlitz et al. teach that the method is directed for non-invasive prenatal genetic testing (see page 32, line 39), as well as targeting DSY14 marker, known to exist on Y-chromosome, the artisans are not explicit in stating that this multicopy marker is present on the Y-chromosome in more than 20 locations (claim 10) or that the fetus from which the cell-free fetal DNA is analyzed is between 4 weeks to 20 weeks (claim 26).
Horlitz et al. do not explicitly teach that the detection is carried out with a microarray (claim 14).
Khamlor et al. teach a well-known established isothermal amplification detection known as LAMP which employs a reporter to detect the presence of a target nucleic acid (“loop primer was labeled with 6-carboxyl-X-rhodamine (ROX), emitting red color under ultraviolet (UV) light, and both Sat1 loop primers were labeled with fluorescein isothiocyanate (FITC), exhibiting green color under UV light”, page 892, 1st column, “[o]range precipitate indicated a male specimen because both the male-specific primers (red) and the internal control primers (green) were used and incorporated into the amplified product … green precipitate indicated a female specimen because only the internal control primers were incorporated in the amplified product”, page 892, 2nd column).
The LAMP reaction was performed for 1 hours (or 60 minutes, see page 892, 2nd column).
The reaction volume is less than 1 ml (“LAMP was conducted in 25-mL reaction”, page 892, 1st column).
The reaction was 100% accurate (“multiplex LAMP showed 100% accuracy in identifying actual sex of the embryos and provides a fast, simple, and cost-effective tool”, Abstract).
Hromadnikova et al. teach a well-established means of typing for baby’s sex via non-invasive means, wherein the sample is taken during 10-18 weeks of pregnancy (see page 235, 2nd column).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the application to combine the teachings of Horlitz et al., Khamlor et al., and Hromadnikova et al., with conventionally known nucleic acid detection means, such as microarrays, thereby arriving at the invention as claimed for the following reasons.
The reason to combine the teachings of the artisans is one of common sense and combination of teachings which yields no more than a predictable outcome.
In KSR, the Supreme Court particularly emphasized “the need for caution in granting a patent based on the combination of elements found in the prior art,” Id. at 415, 82 USPQ2d at 1395, and discussed circumstances in which a patent might be determined to be obvious. Importantly, the Supreme Court reaffirmed principles based on its precedent that “[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” Id. at 415-16, 82 USPQ2d at 1395. The Supreme Court stated that there are “[t]hree cases decided after Graham [that] illustrate this doctrine.” Id. at 416, 82 USPQ2d at 1395. (1) “In United States v. Adams, . . . [t]he Court recognized that when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable result.”
As demonstrated above, Horlitz et al. teach a well-known concept of detecting fetal circulating target nucleic acids from a pregnant blood/plasma sample involving the routine steps of isolating/enriching/detecting means.
While Horlitz et al. did not explicitly teach all types of detection means which could be employed, the artisans specifically suggested that well-known means, such as linear amplification method could be employed for such a detection. Given that the fetal nucleic acid sequences have been well characterized, one of ordinary skill in the art would have had a reasonable expectation of success that the combination of the method of Horlitz et al. and the well-characterized sequences of fetal nucleic acids, and other prior art known means of detection, such as LAMP, a well-known isothermal amplification, or microarrays, would have yielded the same predictable detection outcome. In addition, as evidenced by Khamlor et al., LAMP means would have also yielded a fast and reliable outcome, further aiding as a motivation to combine other detection means known in the art.
As to the detection time being less than 60 minutes, while the assay time of Khamlor et al. was 60 minutes, one of ordinary skill in the art would have had the motivation to reduce the assay time by optimizing the assay conditions of a LAMP assay through empirical determination of general conditions known for a LAMP assay (incubation conditions, temperatures of the reaction, etc.) for the long-recognized need in the art to make assays more accurate and efficient.
Therefore, the invention as claimed is deemed prima facie obvious over the cited references.
Response to Arguments:
Applicants traverse the rejection.
Applicants contend that the Office has not met the burden of establishing a prima facie case of obviousness because the cited references do not teach or suggest a biological sample volume of less than 1 mL (page 6, Response).
Applicants state that the Office “conflates the biological sample volume obtained from a pregnant subject with the amplification reaction volume used in downstream processing” which are “fundamentally different parameters, and the prior art does no teach or suggest the claimed biological sample volume limitation” (page 6, Response).
Applicants state that the LAMP amplification reaction employed by Khamlor may employ 25 mL, but the reaction does not employ that 25 mL of biological sample obtained from a pregnant subject, but refers to an amplification reaction volume (page 7, Response).
Applicants discuss the obvious knowledge that pertain to the difference between a reaction volume and a collected sample volume (page 7, Response), which is not under dispute by the Office.
Applicants also state that the reference made by Horlitz et al. regarding the use of 0.4-1 ml as a sample was taken out of context as “this volume refers to a different kit (the QIAmp CAN kit) used as a reference comparison method, not the method of Horlitz (page 7, bottom to page 8, 1st paragraph, Response).
This argument has been considered but has not been found persuasive.
The rejection is based on a combination of references. The question to be answered is, is there a reasonable motivation to utilize lesser volume of the maternal sample and is there a reasonable expectation of success at doing so?
And while Applicants make much of the Horlitz’ reference made to QIAmp CNA kit not being the artisans’ teachings, what is clear is that Horlitz references that maternal plasma of less than 1 mL can be utilized to obtain cell-free fetal nucleic acid.
The presently rejected claims broadly captures a generalized step of collecting a biological sample from a subject who is pregnant or suspected of being pregnant, said amount of the collected sample collected being less than 1 mL, followed by the isothermal amplification of one of more target fetal nucleic acids in the sample and detecting the reporter molecule indicative of the presence/absence of the target fetal nucleic acid.
As discussed by Horlitz, the artisan teach that plasma sample collected can be less than 1 mL (as referenced to the successful usage of QIAmp CAN kit), and amplifying what is known to be successfully isolated via means such as isothermal amplification, would have been an obvious application.
The Office respectfully maintains that the prior art successfully demonstrates that cell-free fetal DNA can be isolated from less than 1 mL of maternal plasma sample and amplifying that which is successfully isolated via amplification means known in the art, such as PCR, isothermal amplification, linear amplification, would have presented one of ordinary skill in the art a reasonable expectation of success.
The legal standard for “reasonable expectation of success” is provided by case law and is summarized in MPEP 2144.08, which notes “obviousness does not require absolute predictability, only a reasonable expectation of success; i.e., a reasonable expectation of obtaining similar properties. See, e.g., In re O'Farrell, 853 F.2d 894, 903, 7 USPQ2d 1673, 1681 (Fed. Cir. 1988).”
Indeed, Repiska et al. (Clin. Chem. Lab Med., 2013, vol. 51, no. 6, pages 1185-1189) teach the use of QIAmpt CNA kit for isolating cell-free fetal DNA from maternal plasma sample at 500 ml (see page 1186) which are successfully amplified (see page 1186, 2nd column).
Therefore, Applicants’ arguments are not deemed persuasive and the rejection is maintained.
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 2, 7-11, 13-18, and 22-27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/607,329 (reference application) in view of Horlitz et al. (WO 2013/045432 A1, published April 2013).
In addition, claims 2, 7-11, 13-18, and 22-27 are rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,932,907 (herein, “the ‘907 patent”) in view of Horlitz et al. (WO 2013/045432 A1, published April 2013). The claims of the ‘907 patent is virtually identical in the scope as that of the claims of the reference application and therefore, the rationale for the rejection is the same and will not be reproduced. This rejection is not a provisional rejection.
The rejection of the instant claims over the reference application is explicitly discussed below.
Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
With regard to instant claim 2, claims of the reference application also claims a method comprising the steps:
obtaining a biological sample from a subject who is pregnant or suspected of being pregnant comprising fetal nucleic acids, wherein the sample volume is less than 1 ml (“obtaining a 100-750 ml capillary blood sample that was collected from the upper arm of the human subject”, claim 1(a);
performing an amplification on one or more target fetal nucleic acids in the sample to generate reporter molecules if the target nucleic acids are present in the sample (“isolating cell-free nucleic acids from the plasma … performing PCR on the cell-free nucleic acid to detect the presence or absence of fetal Y-chromosome nucleic acids in the capillary blood sample”, claims 1(b)(c)); and
detecting the reporter molecule, wherein detection of the reporter molecules indicates the presence of target fetal nucleic acids in the sample (“the PCR is a real-time quantitative PCR”, claim 10).
With regard to instant claim 7, the sex of the fetus is determined (“presence or absence of fetal Y-chromosome”, claim 1(d)).
With regard to instant claim 8, the target fetal nucleic acid is cell-free fetal DNA (“isolating cell-free nucleic acids from the plasma”, claim 1(c)).
With regard to instant claim 11, the sample is blood/plasma (see above).
With regard to instant claim 16, the biological sample is contacted with a preservative composition and/or a protectant composition (“capillary blood is contacted with a preservative present in the tube”, claim 11).
With regard to instant claim 18, the protectant composition comprises EDTA (see claim 14).
With regard to instant claims 22-25, the plasma is separated (see above) and fetal nucleic acid is isolated therefrom.
With regard to instant claim 26, the sex is determined with at least 90% accuracy (“sex of the fetus is determined with at last 99.5% accuracy”, claim 5).
With regard to instant claim 27, the gestational age of the fetus is between 4-20 weeks (“gestational age of the fetus is 6 weeks to 12 weeks”, claim 9).
Claims of the reference application involves PCR, not isothermal amplification.
Claims of the reference application do not explicitly claim that the target nucleic acid is a single copy or a multi copy target sequence (claim 9), on Y-chromosome (claim 10).
Claims of the reference application do not explicitly teach that the reporter is detectable in less than 60 minutes (claim 13), or the detection is carried out with means of claim 14, or the isothermal amplification means recited in claim 15.
Horlitz et al. teach a well-known means of analyzing extracellular fetal nucleic acids from a variety of sample types and detecting such nucleic acids by a variety of analysis methods known in the art:
“[c]irculating cell-free nucleic acid was isolated from maternal blood samples…”)
“The isolated extracellular nucleic acids and/or a specific target extracellular nucleic acid comprised or suspected of being comprised therein can be identified, quantified, modified, contacted with at least one enzyme, amplified, reverse transcribed, …” (page 32, lines 26-28)
“the isolated extracellular nucleic acids are analyzed to identify and/or characterize a disease or a fetal characteristic … may further comprise a step c) of nucleic acid analysis and/or processing … analysis further processing of the nucleic acids can be performed using any nucleic acid analysis/processing method including, but not limited to amplification technologies, polymerase chain reaction (PCR), isothermal amplification … NASBA … HDA … ” (page 33, lines 5-8)
“detecting the target molecule wherein the detection indicates the presence of target fetal nucleic acids in the sample (“The isolated extracellular nucleic acids and/or a specific target extracellular nucleic acid comprised or suspected of being comprised therein can be identified, quantified, modified, contacted with at least one enzyme, amplified, reverse transcribed, …” (page 32, lines 26-28).
As well, Horlitz et al. teach a known target DYS14 which is located on the Y-chromosome (“triplex qPCR assay for detection of 18S rDNA … DYS14 … and RhD …), wherein DSY14 a Y-chromosome marker and thus can be used as sex typing3), a known mutli-copy marker.
The target fetal nucleic acid is cell-free fetal DNA (“The term ‘extracellular nucleic acids’ or ‘extracellular nucleic acid4’ as used herein, in particular refers to nucleic acids …such as fetal DNA and/or RNA …”, page 10, line 33 to page 11, line 2).
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 combine the teachings of the reference application with the teachings of Horlitz et al., thereby arriving at the invention as claimed because combining prior art known and well-established alternative amplification techniques, such as isothermal amplification, in place of the PCR amplification of the cell-free fetal nucleic acids (of reference application) would have yielded a predictable outcome of amplifying the fetal DNA present in the sample to a level of detection when present.
Therefore, the invention as claimed is deemed prima facie obvious over the cited references.
Conclusion
No claims are allowed.
The instant Office Action contains at least one rejection not necessitated by Amendment and is therefore made, Non-Final.
Inquiries
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Young J. Kim whose telephone number is (571) 272-0785. The Examiner can best be reached from 7:30 a.m. to 4:00 p.m (M-F). The Examiner can also be reached via e-mail to Young.Kim@uspto.gov. However, the office cannot guarantee security through the e-mail system nor should official papers be transmitted through this route.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Gary Benzion, can be reached at (571) 272-0782.
Papers related to this application may be submitted to Art Unit 1681 by facsimile transmission. The faxing of such papers must conform with the notice published in the Official Gazette, 1156 OG 61 (November 16, 1993) and 1157 OG 94 (December 28, 1993) (see 37 CFR 1.6(d)). NOTE: If applicant does submit a paper by FAX, the original copy should be retained by applicant or applicant’s representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED, so as to avoid the processing of duplicate papers in the Office. All official documents must be sent to the Official Tech Center Fax number: (571) 273-8300. Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-1600.
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/YOUNG J KIM/Primary Examiner
Art Unit 1637 June 16, 2026
/YJK/
1 See Blagodatskikh et al. (Mol. Biol. (Mosk), 2010, vol. 44, no. 4, Abstract only).
2 “[r]espective extracellular nucleic acids are also often referred to as cell-free nucleic acids. These terms are used as synonyms herein” (Horlitz, page 10, lines 33-35)
3 See Blagodatskikh et al. (Mol. Biol. (Mosk), 2010, vol. 44, no. 4, Abstract only).
4 “[r]espective extracellular nucleic acids are also often referred to as cell-free nucleic acids. These terms are used as synonyms herein” (Horlitz, page 10, lines 33-35)
Prosecution Insights