DETAILED ACTION
Notice of Pre-AIA or AIA Status
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. Please note that the examiner for this application has changed. Please address future correspondence to Robert T. Crow (Art Unit 1683) whose telephone number is (571) 272-1113.
Continued Examination Under 37 CFR 1.114
3. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 13 November 2025 has been entered.
Non-Compliant Amendments and Status of the Claims
4. This action is in response to papers filed 13 November 2025 in which claims 1, 10, and 21 were amended, claim 3 was canceled, and no new claims were added.
However, Applicant’s amendments fail to comply with 37 CFR 1.121 for the following reason(s): claims 10 and 21 are marked as “currently amended,” but the amendments were already present in the previous version of the claims filed 6 June 2025.
5. It is emphasized that Applicant’s response filed 13 November 2025 has been considered in the interest of customer service and compact prosecution. However, for the response to this Office Action to be complete, Applicant is REQUIRED to file amendments that are compliant with 37 CFR 1.121. Failure to comply with this requirement will be considered nonresponsive.
All previous rejections not reiterated below are withdrawn in view of the amendments.
6. Claims 1-2, 4-7, 10-21, and 23 are under prosecution.
Claim Interpretation
7. The claims are subject to the following interpretation:
A. It is noted that the courts have held that when a claim recites using an old composition or structure and the “use” is directed to a result or property of
that composition or structure, then the claim is anticipated (In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978)). The phrase “for the stabilization of a cell-free nucleic acid (cfNA) population in a blood sample” clearly defines a use of the composition, and thus does not further distinguish the composition over the prior art. See MPEP 2112.02.
B. The preamble of claim 23 recites a “kit.” The specification, however, does not define this term, and so it is being interpreted to encompass any collection of reagents that includes all of the elements of the claims. Any further interpretation of the word is considered an “intended use” and does not impart any further structural limitation of on the claimed subject matter.
Claim Rejections - 35 USC § 112
8. 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.
9. Claim 21 is 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.
Claim 21 is indefinite in the recitation “between about.” The word “between” typically indicates a minimum and/or maximum point; however, the word “between” is controverted by the term “about,” which implies that values above and below the indicated amount are permitted. Therefore, the juxtaposition of these two terms makes it unclear what minimum and/or maximum values are encompassed by the claim.
In Amgen, Inc. v. Chugai Pharmaceutical co., 927 F.2d 1200 (CAFC 1991), the CAFC stated, “[t]he district court held claims 4 and 6 of the patent invalid because their specific activity of “at least about 160,000” was indefinite.” After review, the CAFC states “[w]e therefore affirm the district court’s determination on this issue.” Thus, the CAFC found the phrase “at least about” indefinite where the metes and bounds of the term were not defined in the specification. The phrase “between about” is therefore also deemed indefinite. See MPEP 2173.05(b) III.
Claim Rejections - 35 USC § 103
10. 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.
11. 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.
12. Claims 1-2, 14-16, 19-20, and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Andreasen et al (U.S. Patent Application Publication No. US 2015/0320031 A1, published 12 November 2015) and Doebbler et al (Transfusion 6.2, pages 104/111, published 1966) and, as applied to claims 15-16, as evidenced by Tselepis et al (U.S. Patent Application Publication No. US 2012/0276163 A1, published 1 November 2012) and Dessen et al (U.S. Patent Application Publication No. US 2016/0331777 A1, published 17 November 2016).
Regarding claim 1, Andreasen et al teach an aqueous (i.e., water) solution (paragraph 0132) for use with blood samples (paragraph 0037) comprising polyvinylpyrrolidone and urea (paragraph 0128); it is noted that Andreasen et al teach “at least one additional” of the cryoprotectants polyvinylpyrrolidone and urea; thus, it would have been obvious to include both of the claimed compounds.
In addition, with respect to a mixture of the claimed reagents, the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art (In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).” See MPEP2144.06. It is therefore obvious to provide any mixture of the reagents of the cited prior art.
Andreasen et al further teach the composition comprises apoptosis inhibitors (paragraph 0130). Andreasen et al also teach the composition has the added advantage of having a low toxicity (paragraph 0008). Thus, Andreasen et alt each the known techniques discussed above.
It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to “prove that subject matter shown to be in the prior art does not possess the characteristic relied on” (205 USPQ 594, second column, first full paragraph).
Specifically, Andreasen et al teach the polyvinylpyrrolidone (i.e., a cryoprotectant) is present in 6-20% w/w (paragraph 0138; see also paragraph 0139), which is believed to overlap the claimed range of about 5% to about 30% w/v.
In addition, Doebbler et al teach 7% w/v polyvinylpyrrolidone allows rapid freezing of samples (Abstract). Thus, Doebbler et al teach the known techniques discussed above.
It is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05.01).
The courts have also found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II.
Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Applicant is advised that MPEP 716.01(c) makes clear that “[t]he arguments of counsel cannot take the place of evidence in the record” (In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965)). Thus, Applicant should not merely rely upon counsel’s arguments in place of evidence in the record.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of the cited prior art to arrive at the instantly claimed composition with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in a composition having the added advantage of having a low toxicity as explicitly taught by Andreasen et al (paragraph 0008) and the added advantage of allowing rapid freezing of samples as explicitly taught by Doebbler et al (Abstract). In addition, it would have been obvious to the ordinary artisan that the known techniques of the cited prior art could have been combined with predictable results because the known techniques of the cited prior art predictably result in useful preservation solutions.
Regarding claim 2, the compsition of claim 1 is discussed above. Doebbler e tal tach the PVP has a molecular weight of 20000 Daltons (i.e., 20000; Abstract).
It is reiterated that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists, and that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.
Therefore, the claimed range merely represents an obvious variant and/or routine optimization of the values of the cited prior art.
Applicant is again cautioned against merely relying upon counsel’s arguments in place of evidence in the record.
Regarding claim 14, the composition of claim 1 is discussed above. Andreasen et al teach addition of sodium chloride (paragraph 0128); thus, the solution is a saline solution. Doebbler et al also teach aqueous sodium chloride solutions (page 105).
Regarding claims 15-16, the composition of claim 1 is discussed above. Andreasen et al teach addition of alginate (paragraph 0128), which is a chelator as evidenced by Tselepis et al (i.e., claim 16; paragraph 0028) and an anticoagulant as evidenced by Dessen et al (i.e., claim 15; paragraph 0001).
Regarding claims 19-20, the composition of claim 1 is discussed above. Andreasen et al teach glucose and lactose (paragraph 0128).
Regarding claim 23, the composition of claim 1 is discussed above. As previously noted, the claimed “kit” is merely interpreted as a collection of the claimed structural elements. Doebbler et al also teach blood collection containers (“Containers,” page 105).
It is noted that the courts have found that “the content of the printed matter will not distinguish the claimed product from the prior art (In re Ngai, 367 F.3d 1336, 1339, 70 USPQ2d 1862, 1864 (Fed. Cir. 2004)).” See MPEP 2112.01 III. Therefore, inclusion of any instructions are obvious.
13. Claims 4-7, 15-21, and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Andreasen et al (U.S. Patent Application Publication No. US 2015/0320031 A1, published 12 November 2015) and Doebbler et al (Transfusion 6.2, pages 104/111, published 1966) as applied to claims 1 and 19 above, and further in view of Horlitz et al (PCT International Publication No. WO 2013/045457 A1, published 4 April 2013).
It is noted that while claims 15-16, 19-20, and 23 have been rejected as described above, the claims are also obvious using the interpretation outlined below.
Regarding claims 4-7, 15-21, and 23, the compositions of claims 1 and 19 are discussed above in Section 11.
Neither Andreasen et al nor Doebbler et al teach the claimed apoptosis inhibitors, chelators, glucose concentrations, or kits.
However, Horlitz et al teach compositions for stabilizing blood samples (page 1) comprising a caspase inhibitor (i.e., claim 4; Abstract), including Q-VD-OPh as a caspase inhibitor (i.e., claims 5-6; page 15, line 20) at a concentration of about 50 uM (i.e., claim 7; page 16).
Horlitz et al also teach the anticoagulant chelator K2EDTA (i.e., claims 15-17) having a concentration of about 10 mM (i.e., claim 18 page 26) and a glucose concentration of about 10 mM (i.e., claims 19-21; page 63).
Horlitz et al also teach a blood collection container (page 4) as well as kits (page 32) and instructions (i.e., claim 23; page 56).
It is also reiterated that the courts have found that the content of the printed matter will not distinguish the claimed product from the prior art. Therefore, any instructions are obvious.
Horlitz et al also teach the compositions have the added advantage of being surprisingly effective at stabilizing blood samples (page 4). Thus, Horlitz et al teach the known techniques discussed above.
It is reiterated that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists, and that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.
Therefore, the claimed range merely represents an obvious variant and/or routine optimization of the values of the cited prior art.
Applicant is again cautioned against merely relying upon counsel’s arguments in place of evidence in the record.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Horlitz et al with the previously cited prior art to arrive at the instantly claimed composition with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in a composition having the added advantage having a composition that is surprisingly effective at stabilizing blood samples as explicitly taught by Horlitz et al (page 4). In addition, it would have been obvious to the ordinary artisan that the known techniques of Horlitz et al could have been combined with the previously cited prior art with predictable results because the known techniques of Horlitz et al predictably result in useful preservation solutions.
14. Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Andreasen et al (U.S. Patent Application Publication No. US 2015/0320031 A1, published 12 November 2015) and Doebbler et al (Transfusion 6.2, pages 104/111, published 1966) as applied to claim 1 above, and further in view of Jackson et al (PCT International Publication No. WO 2017/214338 A1, published 14 December 2017).
Regarding claim 10, the composition of claim 1 is discussed above in Section 11.
While Andreasen et al teach an aqueous (i.e., water) solution (paragraph 0132) for use with blood samples (paragraph 0037) comprising polyvinylpyrrolidone and urea (paragraph 0128), neither Andreasen et al nor Doebbler et al teach the claimed urea concentration.
However, Jackson et al teach compositions for stabilizing blood samples (paragraph 0004) comprising urea in a concentration of 100 mM (paragraph 0298), and that the compositions have the added advantage of minimizing nuclease activity (paragraph 01404). Thus, Jackson et al teach the known techniques discussed above.
It is reiterated that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists, and that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.
Therefore, the claimed range merely represents an obvious variant and/or routine optimization of the values of the cited prior art.
Applicant is again cautioned against merely relying upon counsel’s arguments in place of evidence in the record.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Jackson et al with the previously cited prior art to arrive at the instantly claimed composition with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in a composition having the added advantage minimizing nuclease activity as explicitly taught by Jackson et al (paragraph 0104). In addition, it would have been obvious to the ordinary artisan that the known techniques of Jackson et al could have been combined with the previously cited prior art with predictable results because the known techniques of Jackson et al predictably result in useful preservation solutions.
15. Claims 11-14 are rejected under 35 U.S.C. 103 as being unpatentable over Andreasen et al (U.S. Patent Application Publication No. US 2015/0320031 A1, published 12 November 2015) and Doebbler et al (Transfusion 6.2, pages 104/111, published 1966) as applied to claim 1 above, and further in view of Schoenhammer et al (Pharm. Res., vol. 26, pages 2568-2577, published December 2009).
It is noted that while claim 14 has been rejected as described above, the claim is also obvious using the interpretation outlined below.
Regarding claims 11-14, the composition of claim 1 is discussed above in Section 11.
While Andreasen et al teach multimers of ethylene glycol (e.g., di- and tri-ethylene glycol; paragraph 0128), neither Andreasen et al nor Doebbler et al teach the claimed dimethyl ether.
However, Schoenhammer et al teach the use of 500 Dalton dmPEG (i.e., claims 11-12; Title) including 20% w/w (i.e., claim 13; “Viscosity of Polymer Solutions”), as well as 0.9% sodium chloride solutions (i.e., the saline solution of claim 14; “Hemolysis Test of Solvents”). Schoenhammer et al also teach the solutions have the added advantage low hemolytic activity (“Conclusion”). Thus, Schoenhammer et al teach the known techniques discussed above.
It is reiterated that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists, and that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.
Therefore, the claimed range merely represents an obvious variant and/or routine optimization of the values of the cited prior art.
Applicant is again cautioned against merely relying upon counsel’s arguments in place of evidence in the record.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Schoenhammer et al with the previously cited prior art to arrive at the instantly claimed composition with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in a composition having the added advantage low hemolytic activity as explicitly taught by Schoenhammer et al (“Conclusion”). In addition, it would have been obvious to the ordinary artisan that the known techniques of Schoenhammer et al could have been combined with the previously cited prior art with predictable results because the known techniques of Schoenhammer et al predictably result in useful preservation solutions.
Response to Arguments
16. Applicant’s arguments with respect to the previous prior art rejections of the claims have been considered but are moot in view of the new grounds of rejection necessitated by the amendments.
Conclusion
17. No claim is allowed.
18. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Robert T. Crow whose telephone number is (571)272-1113. The examiner can normally be reached M-F 8:00-4:30.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Gussow can be reached at 571-272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Robert T. Crow
Primary Examiner
Art Unit 1683
/Robert T. Crow/Primary Examiner, Art Unit 1683