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 .
Priority
This application 17/714,778 filed on 04/06/2022 claims the benefit of provisional U.S. Patent Application No. 63/171,547, filed on 04/06/2021.
The priority date of claim 28 and its dependent claims 29, 31, and 33 is determined to be 04/06/2021, the filing date of provisional U.S. Patent Application No. 63/171,547.
Status of Claims
Applicant’s amendments to claims filed 02/18/2026 in response to the Non-Final Rejection mailed 10/21/2025 are acknowledged.
Claims 1, 9, 26, 28, 33, 44, 47, 97, 98, 102 and 103 are amended.
Claims 1-2, 7, 9, 23, 26, 28-29, 31, 33, 44-45, 47, 97-98 and 102-103 are pending and claims 28-29, 31, 33 are under examination.
Response to Remarks filed 02/18/2026
The amendments and arguments presented in the papers filed 02/18/2026 ("Remarks”) have been thoroughly considered. The issues raised in the Office action dated 10/21/2025 listed below have been reconsidered as indicated.
a) The objections to the specification regarding the presence of hyperlinks and the use of trade names or marks are withdrawn in view of the amendments to the specification.
b) The has been withdrawn in view of the amendments to the claims.
c) The 35 USC 112(b) indefiniteness rejections of claims 28, 29, 31, and 33 have been withdrawn in view of the amendments to the claims.
d) The rejection of claims 28, 29, 31, and 33 under 35 U.S.C. 102 as being anticipated by Lindeman et al. (WO 2010/127399) are withdrawn in view of the amendments to the claims.
e) The provisional rejection on the ground of non-statutory obviousness-type double patenting over co-pending Applications 18/286,073 and 18/286,075 are withdrawn in view of the amendments to the claims.
New and modified grounds of rejection necessitated by amendment are detailed below and this action is made FINAL.
Claim Objections
Claim 28 is objected to because of the following informalities: The claim recites the limitation “SLC21A”. It assumed this is a typographical error intended to be “SLC2A1”. Appropriate correction is required.
Claim Rejections - 35 USC § 101 - updated
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 28, 29, 31, and 33 remain/are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
These are modified rejections necessitated by claim amendments.
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.
Based upon consideration of the claims as a whole, as well as consideration of elements/steps recited in addition to the judicial exception, the present claims fail to meet the elements required for patent eligibility.
Step 1
The claimed invention is directed to the statutory category of a process.
Step 2A, Prong One
The claim is taken to be directed to an abstract idea, a judicial exception.
Claim 28 is directed to a method comprising “(b) comparing the level of the breast cancer marker in the biological sample with a predetermined threshold value ---”. This limitation is an abstract mental process (see MPEP 2106.04(a)(2)(III)). As written, the comparing step encompasses the mental step of looking at data and making mental judgements.
Claims 29, 31, and 33 depend from claim 28 , and require the same step of “comparing the level of the breast cancer marker in the biological sample with a predetermined threshold value” and requires the same correlation.
Regarding Step 2A, prong one, the claims further recite the judicial exception of a law of nature. Claim 28 recites “wherein an increased level of SLC21A when compared to the predetermined threshold value indicates that the subject has an ER-negative-like molecular subtype of ER-positive breast cancer”. Claim 33 recites “ (a) -- wherein a decreased level of the one or more markers selected from the group consisting of AGR3, ADIRF, REEP6, STARD1O, MLPH, ABAT, THSD4, ACADSB, NME3, CIRBP, SSH3, PHPT1, GMPR2, PREX1, FIS1, HAGH, HSD17B8, AHCYL1, NT5C, and MDP1 -- indicates that the subject has ER- negative-like molecular subtype of ER-positive breast cancer; (b) wherein an increased level of the one or more markers selected from the group consisting of ANKS1A, GART, SRPK1, NCBP1, TJP2, PNP, TIA1, MTHFD2, PLOD1, KPNA2, ASNS, MTHFD1L, and FSCN1 -- indicates that the subject has ER-negative-like molecular subtype of ER-positive breast cancer —" The claims recite the judicial exception of a law of nature. The claims recite the correlation between molecular subtypes of ER-positive breast cancer in a subject and an alteration in the expression of the SLC2A1 gene (claim 28); AGR3, ADIRF, REEP6, STARD1O, MLPH, ABAT, THSD4, ACADSB, NME3, CIRBP, SSH3, PHPT1, GMPR2, PREX1, FIS1, HAGH, HSD17B8, AHCYL1, NT5C, and MDP1 genes (claim 33 part a), and ANKS1A, GART, SRPK1, NCBP1, TJP2, PNP, TIA1, MTHFD2, PLOD1, KPNA2, ASNS, MTHFD1L, and FSCN1 genes (claim 33 part b). These relationships is a natural phenomenon that exists apart from any human action and constitutes a law of nature. A correlation that preexists in the human is an unpatentable phenomenon.
Step 2A, Prong Two
The exception is not integrated into a practical application of the exception. The claims do not recite any additional elements that integrate the exception into a practical
While claim 28 recites ” (a) detecting the level of a breast cancer marker in a biological sample from the subject”, this is not an integration of the exception into a practical application. Instead, this element is data gathering required to perform the method.
Claim 28 further recites “(c) administering a treatment regimen to the subject, wherein the treatment regimen is selected from the group consisting of radiation therapy, hormone therapy, chemotherapy, immunotherapy, surgery, or any combination thereof.” The recited treatment is at such a high level of generality that it is a mere invitation to "apply" the judicial exceptions and does not constitute a particular treatment. Further, the limitation as written is directed to any subject and encompasses all subjects in which the level of SCL2A1 was detected at any level.
Claim 33 further recites “(c) wherein the level of the breast cancer marker is detected by one or more of HPLC/UV-Vis spectroscopy, enzymatic analysis, mass spectrometry, NMR, immunoassay, ELISA, chromatography, or any combination thereof, or by determining the level of its corresponding mRNA in the biological sample”. This limitation is mere data gathering required to perform the method. Further it is noted that, as written, this limitation is presented in the alternate and is not required.
Step 2B
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception. The claim does not add a specific limitation other than what is well-understood, routine, and conventional in the field. Steps directed to detecting the levels of markers in a biological sample are techniques that are routine, conventional, and well-known in the art as demonstrated in the 102 rejection documented below. Additionally, the administration of a treatment is required at ahigh level of generality that does not amount to significantly more than the judicial exception.
Response to Arguments against Claim Rejection - 35 U.S. C § 101
The response asserts that the claimed methods include an additional element that applies or uses a judicial exception to effect a particular treatment for an ER-negative-like molecular subtype of an ER-positive breast cancer (p. 16) In support of this assertion, the response cites the specification :” -- Monitoring and/or treatment decisions
can be made by a physician based on the further classification of the breast cancer as having an ER-positive-like or ER-negative-like molecular subtype”(p. 17).
Applicant's arguments have been fully considered but are not persuasive.
The claims as amended add administering a treatment at a high level of generality and do not recite an action directed towards a particular treatment or prophylaxis for a disease or medical condition. As such it is merely an intended use or invitation to "apply" the judicial exception. Further, the added treatment steps are not directed to a particular subject, but to any subject.
The response further asserts that the elements of detecting the level of a breast cancer
marker in a biological sample from the subject, wherein the breast cancer marker comprises SLC2A1 and wherein an increased level of SLC21A [sic] when compared to the predetermined threshold value indicates that the subject has an ER-negative-like molecular subtype of an ER-positive breast cancer, are novel and inventive, and are not routine, conventional, and well-known in the art (p. 17).
Applicant's arguments have been fully considered but are not persuasive.
As described in the rejection above, detecting the level of a breast cancer
marker in a biological sample from the subject, is a routine and conventional method well known in the art. The additional limitation regarding “wherein an increased level of SLC21A --- indicates that the subject has an ER-negative-like molecular subtype of an ER-positive breast cancer” is a natural phenomenon that is unpatentable.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 28, 29, 31, and 33 are rejected under 35 U.S.C. 103 as being unpatentable over Pinheiro et al. (GLUT1 and CAIX expression profiles in breast cancer correlate with adverse prognostic factors and MCT1 overexpression. 2011. Histol Histopathol (2011) 26: 1279-1286).
These are new rejections necessitated by claim amendments filed on xxREM.
Regarding claim 28 part (a), Pinheiro teaches the evaluation of GLUT1 (SLC2A1) expression in breast cancer, which is associated with a basal-like subtype (Abstract). Pinheiro teaches performing immunohistochemistry on breast carcinoma tissues (p. 1280, col. 2), which reads on detecting the level of a breast cancer marker in a biological sample from a subject. Regarding part (b), Pinheiro teaches scoring immunohistochemical reactions for number of stained cells and intensity of staining (p. 1281, col. 1-2) and grouping samples with scores of 0-2 as negative and 3-6 as positive, which reads on comparing the level of the breast cancer marker with a predetermined threshold value. Pinheiro further teaches GLUT1 positive samples (samples with an increased level of SLC21A when compared to the predetermined threshold value) that are ER-negative and GLUT1 positive samples that are ER-positive (i.e. an ER-negative-like molecular subtype of ER-positive breast cancer) (Table 2).
Regarding part (c), Pinheiro teaches strengthening the clinicopathological value using GLUT1 expression in breast cancer, i.e. using the GLUT1 marker to improve diagnoses and determine treatments (p. 1280, col. 1). Pinheiro further teaches that the development of therapeutic approaches targeting these particular metabolic features (including GLUT1 expression) could be a promising strategy to be explored in the treatment of basal-like breast tumors (p. 1284, col. 2).
Pinheiro does not teach specifically administering a treatment regimen to the subject, wherein the treatment regimen is selected from the recited group of the claim.
It would have been prima facie obvious to a person of ordinary skill in the art to arrive at the instantly claimed invention before the effective filing date of the claimed invention from the teachings of Pinheiro. The modification would have entailed selecting a therapy for aggressive breast cancer. One of skill in the art would have known standard treatment options of radiation therapy, hormone therapy, chemotherapy, immunotherapy, and surgery, each of which was well-known and conventional at the time of filing. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 29, Pinheiro teaches tumors positive for ER were classified as luminal, including luminal B (p. 1280, col. 2).
Regarding claim 31, Pinheiro teaches the biological sample is breast carcinoma tissue (p. 1280, col. 2).
Regarding claim 33, Pinheiro teaches detecting the level of the breast cancer marker by immunohistochemistry, which reads on part (e), detecting by immunoassay.
Double Patenting - New
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.
(I). Claims 28, 29, 31, and 33 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-3, 6, 19, 22, 24, 25, 28, 28, 39, 42, 52, 53, 56, 66, 67, 70, 91, 92, 96, and 97 of copending Application No. 18/286,073 in view of Pinheiro et al. (GLUT1 and CAIX expression profiles in breast cancer correlate with adverse prognostic factors and MCT1 overexpression. 2011. Histol Histopathol (2011) 26: 1279-1286).
Although the claims at issue are not identical, they are not patentably distinct from each other because both are directed to methods of detecting breast cancer comprising detecting breast cancer markers levels and determining subtype by comparing marker levels to a threshold. .
Regarding instant claim 28, copending claims 1, 24, and 38 require (a) detecting the level of a breast cancer marker in a biological sample from the subject, wherein the breast cancer marker comprises one or more markers selected from Tables 1 and 2; and(b) comparing the level of the breast cancer marker in the biological sample with a predetermined threshold value; wherein the molecular subtype is determined based on the level of the breast cancer marker above or below the predetermined threshold value. Copending claim 22 requires selecting a treatment regimen based on the molecular subtype of breast cancer in the subject, including selecting the treatment from radiation, chemotherapy, and others.
Copending claims do not require wherein the breast cancer marker comprises SLC21A or wherein an increased level of SLC21A when compared to the predetermined threshold value indicates that the subject has an ER-negative-like molecular subtype of ER-positive breast cancer.
The teachings of Pinheiro as they relate to these claims are given previously in this office action and are fully incorporated here.
Regarding instant claim 29, copending claim 52 requires obtaining a sample from the subject having luminal A1-like breast cancer.
Regarding instant claim 31, copending claims 3, 25 and 39 require the biological sample comprises a breast tissue sample or a breast tumor tissue sample;
Regarding instant claim 33, copending claims 6, 28, 42, 56, and 70 require the level of the breast cancer marker is detected by one or more of HPLC/UV- Vis spectroscopy, enzymatic analysis, mass spectrometry, NMR, immunoassay, ELISA, chromatography, or any combination thereof, or by determining the level of its corresponding mRNA in the biological sample, satisfying the requirement of part (e) of instant claim 33.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
(II). Claims 28, 29, 31, and 33 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1,2,6,12, 15,20, 21,31, 32, 38,40,45,46,56-58,61,62,69, and 76 of copending Application No. 18/286,075 in view of Pinheiro et al. (GLUT1 and CAIX expression profiles in breast cancer correlate with adverse prognostic factors and MCT1 overexpression. 2011. Histol Histopathol (2011) 26: 1279-1286).
Although the claims at issue are not identical, they are not patentably distinct from each other because both are directed to assessing breast cancer markers and comparing levels to a threshold that indicate ER-positive breast cancer.
Regarding instant claim 28, copending claim 1 requires (a) detecting the level of a breast cancer marker in a biological sample from the subject, wherein the breast cancer marker comprises one or more markers selected from Tables 1 and 2; and (b) comparing the level of the breast cancer marker in the biological sample with a predetermined threshold value; wherein the level of the breast cancer marker above or below the predetermined threshold value indicates that the subject is at risk for progression of ER positive breast cancer. Copending claim 31 requires (a) diagnosing ER positive breast cancer in the subject;(b) detecting the level of a breast cancer marker in a biological sample from the subject, wherein the breast cancer comprises one or more markers selected from Tables 1 and 2; and(c) comparing the level of the breast cancer marker in the biological sample with a predetermined threshold value; wherein the level of the breast cancer marker above or below the predetermined threshold value indicates that the subject is at an increased risk for ER positive breast cancer progression. Regarding part (c) of the instant claim, copending claims 21 and 46 require selecting a treatment regimen based on the risk of progression of breast cancer in the subject; wherein the treatment regimen is selected from the group consisting of radiation therapy and chemotherapy among others.
Copending claims do not require wherein the breast cancer marker comprises SLC21A or wherein an increased level of SLC21A when compared to the predetermined threshold value indicates that the subject has an ER-negative-like molecular subtype of ER-positive breast cancer.
The teachings of Pinheiro as they relate to these claims are given previously in this office action and are fully incorporated here.
Regarding instant claim 29, copending claims 6 and 32 require the estrogen receptor (ER) positive breast cancer is luminal B1 breast cancer
Regarding instant claim 31, copending claim 12 and 38 require the biological sample comprises a breast tissue sample or a breast tumor tissue sample.
Regarding instant claim 33, copending claims 20 and 45 require the level of the breast cancer marker is detected by one or more of HPLC/UV-Vis spectroscopy, enzymatic analysis, mass spectrometry, NMR, immunoassay, ELISA, chromatography, or any combination thereof, or by determining the level of its corresponding mRNA in the biological sample, satisfying part (e) of instant claim 33.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/JESSICA GRAY/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
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