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 .
Election/Restrictions
Applicant’s election without traverse of Group in the reply filed on 03/26/2026 and the species elections of the panel of lines 2-46 in claim 1, of the panel of lines 14-16 of claim 2, of beads in claim 5, of antibody in claim 6 & 16, of immunoassay in claim 17, and of post-menopausal status in claim 18 in the reply filed on 08/07/2026 is acknowledged. Group II, claims 9-12 & 14, Group III, claim 13, and Group IV, claims 19-21, are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
A first office action on the merits of claims 1-8, 15-18, & 22 is set forth herein and claims 9-14 & 19-21 are withdrawn from consideration.
Nucleotide and/or Amino Acid Sequence Disclosures
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings, in Figure 1, are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
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 4, 5, & 16 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 4, the claim recites the limitation “the capture reagents” in line 1 of the claim and there is insufficient antecedent basis for this limitation in the claim and it is unclear if it is meant to refer back to the singular form of “a separate capture reagent” in claim 3, from which claim 4 depends from.
Regarding claim 16, the claim recites the limitation “the capture reagent” in line 1 of the claim and there is insufficient antecedent basis for this limitation in the claim.
Claim 5 is rejected due to its dependence on claim 4.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-8, 15-18, & 22 are rejected under 35 U.S.C. 101 because the claimed invention is directed to product of nature without significantly more. This judicial exception is not integrated into a practical application and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons set forth below.
35 U.S.C. § 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. M.P.E.P. § 2106. Regarding judicial exceptions, “[p]henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972); see also M.P.E.P. § 2106, part II.
The unpatentability of natural products was confirmed by the U.S. Supreme Court in Association for Molecular Pathology v. Myriad Genetics, Inc., , 133 S. Ct. 2107, 2116, (2013).
Claims Analysis:
As set forth in MPEP 2106, the claims have been analyzed to determine whether they are directed to one of the four statutory categories (STEP 1). The claims were then analyzed to determine if they recite a judicial exception (JE) (STEP 2A, prong 1) [Mayo Collaborative Services v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012), Alice Corp. Pry. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014)]. The claims were then analyzed to determine whether they recite an element or step that integrates the JE into a practical application (STEP 2A, prong 2) [Vanda Pharmaceuticals Inc., v. West-Ward Pharmaceuticals, 887 F.3d 1117 (Fed. Cir. 2018)]. In the absence of a step(s) or element(s) that integrate the JE into a practical application, the additional elements/steps have been considered to determine whether they add significantly more to the JE (STEP 2B) [Mayo Collaborative Services v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012), Alice Corp. Pry. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014)]. It was found that the present claims fail to meet the elements required for patent eligibility.
The claims are directed to nucleic acid sequences and kits comprising them, and as such are directed to products. Accordingly, the claims are directed to one of the four statutory categories of invention.
The claims are drawn to nucleic acid sequences including DNA, which comprise a panel of gene markers comprising genes TT, ApoA1, β2M, Tfr, CA125, HE4, FSH, etc. A panel of gene markers comprising genes TT, ApoA1, β2M, Tfr, CA125, HE4, FSH, etc. are naturally occurring sequences. As such the claims are directed to a product of nature which is a judicial exception.
This judicial exception is not integrated into a practical application because the nucleic acid molecules encompassed by the claims convey the same genetic information as their naturally occurring counterparts. The Supreme Court has made clear "separating [DNA] from surrounding genetic material is not an act of invention" Myriad, 133 S. Ct. at 2117. In Myriad v. Ambry CAFC 2014-1361,1366, December 17, 2014, the CAFC further (regarding a claim directed to a pair of primers) stated “In fact, the naturally occurring genetic sequences at issue here do not perform a significantly new function. Rather, the naturally occurring material is used to form the first step in a chain reaction—a function that is performed because the primer maintains the exact same nucleotide sequence as the relevant portion of the naturally occurring sequence. One of the primary functions of DNA’s structure in nature is that complementary nucleotide sequences bind to each other. It is this same function that is exploited here—the primer binds to its complementary nucleotide sequence. Thus, just as in nature, primers utilize the innate ability of DNA to bind to itself.”
With regard to claim 22, although the claim recites a “kit” comprising the panel of marker nucleic acids as well as instructions, these elements do not add meaningful limitations to the claims as they are merely nominal or token extra solution activity and are nothing more than an attempt to generally link the product of nature into a particular technological environment. Furthermore, these limitations do not change the structures of the encompassed natural products.
The detection agents encompassed by the claims include nucleic acid sequences comprising a panel of gene markers comprising genes TT, ApoA1, β2M, Tfr, CA125, HE4, FSH, etc., as well as fragments of the naturally occurring genes. None of these molecules or cells are patent eligible, whether isolated or not, pursuant to the Supreme Court decision in Association for Molecular Pathology v. Myriad Genetics Inc., US (June 13, 2013). Accordingly, the claims are rejected as being directed to non patentable subject matter.
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) 1-8, 16-18, & 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Monroe (WO 2014/182806 A1, November 2014), as cited in the IDS dated 03/28/2024, in view of Mansfield (United States Patent Application Publication US 2016/0245818 A1, August 2016), as cited on the IDS dated 09/19/2022.
Regarding claim 1, Monroe teaches a panel of markers for pre-operatively assessment of ovarian tumors in a variety of subject’s having ovarian cancer types with a panel comprising Transthyretin (TT or prealbumin), Apolipoprotein A-1 (ApoA-1), beta 2-micorgobulin (beta 2M), transferrin (Tfr), cancer antigen 125 (CA125), HE4, and FSH (abstract lines 1-11; pg. 2 lines 4-11; pg. 4 lines 1-4; Fig. 1).
Monroe does not teach that the panel comprises one or more markers selected from a group comprising Breast Cancer 1 (BRCA1).
Mansfield teaches a biomarkers for ovarian cancer comprising panels of biomarkers comprising CA125, ApoA1, Beta2M, HE4, FSH, and BRCA-1 (paragraph [0027] lines 1-12; paragraph [0031] lines 1-21; paragraph [0044] lines 9-14; paragraph [0075] lines 1-33). Mansfield also teaches that these panels of biomarkers for ovarian cancer are highly accurate for determining presence and risk of ovarian cancer (paragraph [0040] lines 1-6).
Monroe and Mansfield are considered to be analogous to the claimed invention because they are all in the same field of panels of biomarkers for determining risk of ovarian cancer. 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 panel comprising Transthyretin (TT or prealbumin), Apolipoprotein A-1 (ApoA-1), beta 2-micorgobulin (beta 2M), transferrin (Tfr), cancer antigen 125 (CA125), HE4, and FSH in Monroe to incorporate the biomarker of BRCA-1 in the ovarian cancer panel as taught in Mansfield because Mansfield teaches that these panels of biomarkers for ovarian cancer are highly accurate for determining presence and risk of ovarian cancer.
Regarding claim 2, Monroe teaches a panel of markers for pre-operatively assessment of ovarian tumors in a variety of subject’s having ovarian cancer types with a panel comprising Apolipoprotein A-1 (ApoA-1), transferrin (Tfr), cancer antigen 125 (CA125), HE4, and FSH (abstract lines 1-11; pg. 2 lines 4-11; pg. 4 lines 1-4; Fig. 1).
Monroe does not teach that the panel comprises Breast Cancer 1 (BRCA1) and Breast Cancer 2 (BRCA2).
Mansfield teaches a biomarkers for ovarian cancer comprising panels of biomarkers comprising CA125, ApoA1, Beta2M, HE4, FSH, BRCA-1, and BRCA-2 (paragraph [0027] lines 1-12; paragraph [0031] lines 1-21; paragraph [0044] lines 9-14; paragraph [0075] lines 1-33). Mansfield also teaches that these panels of biomarkers for ovarian cancer are highly accurate for determining presence and risk of ovarian cancer (paragraph [0040] lines 1-6).
Monroe and Mansfield are considered to be analogous to the claimed invention because they are all in the same field of panels of biomarkers for determining risk of ovarian cancer. 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 panel comprising Apolipoprotein A-1 (ApoA-1), transferrin (Tfr), cancer antigen 125 (CA125), HE4, and FSH in Monroe to incorporate the biomarkers of BRCA-1 and BRCA-2 in the ovarian cancer panel as taught in Mansfield because Mansfield teaches that these panels of biomarkers for ovarian cancer are highly accurate for determining presence and risk of ovarian cancer.
Regarding claim 3, Monroe teaches the biomarkers are bound to a biospecific capture reagent (each of the markers are bound to a separate capture reagent) (pg. 28 lines 3-5).
Regarding claims 4 & 5, Monroe teaches the capture reagent is bound to a solid phase comprises a bead (pg. 28 lines 6-7).
Regarding claim 6, Monroe teaches the capture reagent is an antibody (pg. 28 lines 3-5).
Regarding claim 7, Monroe teaches the biomarkers are bound to a biospecific capture reagent (each capture reagent specifically binds to one of the markers) (pg. 28 lines 3-5).
Regarding claim 8, Monroe teaches the panel of markers for use in pre-operatively assessing a subject’s risk of having ovarian cancer (pg. 4 lines 1-4).
Regarding claim 16, Monroe teaches the capture reagent is an antibody (pg. 28 lines 3-5).
Regarding claim 17, Monroe teaches the markers in the panel are detected by (characterized by) immunoassay (pg. 28 lines 3 & 21-24).
Regarding claim 18, Monroe teaches assessing clinical markers of ovarian cancer comprising assessing post-menopausal status (pg. 67 claim 29 lines 1-3).
Regarding claim 22, Monroe teaches a kit for aiding in the diagnosis of ovarian cancer comprising the panel of biomarkers and instructions for use in pre-operatively assessing a subject’s risk of having ovarian cancer (pg. 45 lines 29-32; pg. 46 lines 16-20).
Claim(s) 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Monroe (WO 2014/182806 A1, November 2014), as cited in the IDS dated 03/28/2024, and Mansfield (United States Patent Application Publication US 2016/0245818 A1, August 2016), as cited on the IDS dated 09/19/2022, as applied to claims 1-8, 16-18, & 22 above, and further in view of Asante (Asante et al.; Cancer Letters, Vol. 468, pages 59-71, October 2019), as cited in the IDS dated 03/28/2024.
The teachings of Monroe and Mansfield with respect to claims 1 & 8 are discussed above.
Regarding claim 15, Monroe and Mansfield does not teach the one or more markers are characterized by detecting cell-free tumor DNA.
Asante teaches a method of assessing biomarkers, comprising CA125, for ovarian cancer through circulating cell-free tumor DNA enabling a minimally-invasive means for patient monitoring during clinical course of ovarian cancer in a patient (abstract lines 1-8; pg. 63-66 paragraph bridging pg. 63 & 66 lines 1-7; pg. 66 column 1 1st full paragraph lines 1-8).
Monroe, Mansfield, and Asante are considered to be analogous to the claimed invention because they are all in the same field of panels of biomarkers for determining risk of ovarian cancer. 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 panel of markers for ovarian cancer in Monroe to incorporate characterization of the markers by detecting cell-free tumor DNA as taught in Asante because Asante teaches that circulating cell-free tumor DNA assessment for markers of ovarian cancer is minimally-invasive and enables monitoring during the clinical course of ovarian cancer.
Conclusion
Claims 1-8, 15-18, & 22 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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Winston Shen can be reached at (571) 272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BAILEY BUCHANAN/Examiner, Art Unit 1682
/JEHANNE S SITTON/Primary Examiner, Art Unit 1682
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