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 .
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.
Status of Claims
Claims 1 and 3-18 pending.
Response to Arguments/Amendments
Acknowledgement is made of Applicant’s intention for claims to be interpreted under “Interpretation 1” as outlined in Non-final Office Action mailed 03 July 2025 (see pg. 6, last paragraph of Remarks) and therefore Applicant’s remarks are fully responsive. Therefore, the response to arguments outlined below are in response to Applicant’s arguments under “Interpretation 1”, however, note that both interpretations of the claims are still included in this office action in the event Applicant chooses to change their intended interpretation in future correspondence.
Claim Interpretation 2:
In view of Applicant’s amendments filed 05 January 2026, rejection of claims 9 and 11-16 under 35 U.S.C. 102(a)(1) is hereby maintained.
In view of Applicant’s amendments filed 05 January 2026, rejection of claims 1, 3-8, 10 and 17-18 under 35 U.S.C. 103 is hereby maintained.
Claim Interpretation 1:
In view of Applicant’s amendments filed 05 January 2026, rejection of claims 1 and 3-18 under 35 U.S.C. 101 is hereby maintained.
Applicant's arguments filed 05 January 2026 have been fully considered but they are not persuasive in regards to the rejection of claims 1 and 3-18 under 35 U.S.C. 101. Applicant argues that the recited judicial exception of the instant claims effect a particular treatment for cancer that has more than a nominal or insignificant relationship to the exception and therefore integrates the recited judicial exception into a practical application thus overcoming the rejection under 35 U.S.C. 101 (see pgs. 7-8 of Remarks). However, “radiation therapy” is a very well-known type of cancer treatment and thus extremely generalized. Secondly, there is nothing in the instant claims that recites how administering radiation therapy is particular to identifying a subject is “not at an increased risk of tumor recurrence” or “not at increased risk of one more late effects” as recited in the instant claims. Thus, administering radiation therapy does not apply or use the exception in a meaningful way. In other words, while radiation therapy is a known treatment for cancer, there is no specific link or particular reason why not having an increased risk of tumor recurrence or one or more late effects in a cancer patient would be related to administering radiation therapy (see MPEP 2106.04(d)(2)).
Applicant’s arguments, see pgs. 8-12 of Remarks, filed 05 January 2026, with respect to the rejection of claims 1, 3, 5, 7, 9-11, 17, and 18 under 35 U.S.C. 103 have been fully considered and are persuasive. The rejection has been withdrawn.
CLAIM INTERPRETATION 1:
Novel over Prior Art
Claims 1 and 3-18 appear to be novel over the prior art. The closest prior art to the instant application is United States Patent Application Publication US 2016/0160287 to Lambin et al. (herein Lambin); United States Patent US 11,686,731 to Mills et al. (herein Mills) with a priority date PCT date 05 Jan 2016; “Geranylgeranyl diphosphate synthase as a novel cancer therapeutic target” to Dudakovic; “Metabolic profiling reveals key metabolic features of renal cell carcinoma” to Catchpole et al. (herein Catchpole); United States Patent Application Publication US 2018/0246112 to Lane et al. (herein Lane); “Sphingolipids in cancer” to Furuya et al. (herein Furuya); “The autotaxin-lysophosphatidic acid-lysophosphatidic acid receptor cascade: proposal of a novel potential therapeutic target for treating glioblastoma multiforme” to Tabuchi; United States Patent Application Publication US 2017/0343567 to Bitenc et al. (herein Bitenc); International Publication WO 2017/079763 to Alexander et al. (herein Alexander); United States Patent Application Publication to Sugimoto et al. (herein Sugimoto); and United States Patent Application Publication US 2017/0199978 to Landis.
Lambin discloses using mitochondrial DNA variation (i.e., component profile) in cancer patients to successfully predict whether a subject will develop radiation-induced toxicity (i.e., adverse reaction) after ionizing radiotherapy. Incorporation of the mtDNA information in personalized radiation therapy planning might eventually allow for escalating doses in patients predicted to be at low risk for radiation induced toxicity, improving their chance of disease free survival (see [0008-0013]). In other words, Lambin discloses determining a cancer patient’s risk of an adverse reaction to radiation therapy and administering radiation therapy if said patient’s risk is considered low. Radiation-induced toxicity after ionizing radiotherapy reads on “one or more late effects” as recited in the instant claim.
Mills discloses a method for providing prognosis for a subject with prostate cancer, or selecting a subject with prostate cancer for treatment with a particular therapy, comprising: (a) detecting the level of LRG1 polypeptide in a sample from a subject using an in vitro assay and (b) comparing the level of LRG1 polypeptide to a reference level of LRG1 polypeptide wherein an altered amount is an indication that a subject is likely to respond favorably to a particular treatment. In some cases elevated amounts of LGR1 polypeptide in the biological sample compared to the reference level are indicative of an increased risk of disease recurrence (i.e., tumor recurrence) in the subject following treatment with surgery or radiotherapy (see Cols. 2-3, Summary of Invention & Col. 8, lines 34-52)).
Dudakovic discloses GGPP plays a role in cancer cell development (see pg. 14, 2nd paragraph) and that 3-hydroxy-3-methylglutaryl-coenzyme A and geranyl diphosphate (i.e., geranyl pyrophosphate) are intermediates in the pathway for the production of geranylgeranyl diphosphate (GGPP) (see pg. 1, 2nd paragraph – pg. 2, 1st paragraph)
Catchpole discloses that metabolic changes play a pivotal role in the biology of cancer including metabolites of glucose (see abstract) and that renal cell carcinoma (RCC) tends to be characterized by metabolites associated with glucose metabolism, such as glucose-1-phosphate (see pg. 113).
Lane discloses detecting lipids in humans suspected of having cancer (see abstract), wherein the lipids can include LPI 16:1.
Furuya discloses ceramide pathways have been implicated in cancer development and progression (see abstract). Furuya discloses that Cer 24:0 is shown to be significantly raised in malignant tumors as compared to normal tissue (see pg. 571, 1st paragraph).
Tabuchi discloses that lysophosphatidic acid is well recognized to be involved in tumorigenesis of cancers (see abstract) and that specifically both LPA 16:0 and LPA 18:0 expressions vary with the progression of glioblastoma multiforme (GBM) (see pg. 5, 2nd Col., 2nd paragraph).
Bitenc discloses sets of metabolite and lipid markers that can be used in the detection of early stage colorectal cancer and/or early development of adenomatous polyps (see abstract), wherein the markers include LPC 20:2 (see Table 2).
Alexander discloses that metanephrines are a known tumor marker (see pg. 20-21, line 18 - line 10; pg. 78-79, line 25 – line 18; pg. 83, line 17 – line 32; pg. 87-88, line 20 – line 17; pg. 108 lines 9 – 26; pg. 136-139, line 25 – line 2; pg. 211, lines 13-26; pg. 311, claim 136; pg. 313, claim 143; and pg. 317, claim 166).
Sugimoto discloses using metabolites for detecting cancer (see abstract). Sugimoto discloses comparing metabolite levels in patients with breast cancer to healthy subjects, wherein one of the metabolites is Pantothenate (see [0143], Table 7-4, [0147]; Table 8-4).
Landis discloses a plurality of analytes, including tryptophan and xanthurenic acid (see [0009]) determining if the analyte is above or below a specified normal limit (see [0005]) wherein the analyte is used to assess a biomarker for a physiological state including cancer. (see [0010]).
However, none of the cited prior art, alone or in combination, teaches nor fairly suggests the specific component profiles of (a), (b), or (c) of claim 1 or claim 9. Tables 7, 11, and 15 of the disclosure show that the component profiles of (a), (b), and (c) of independent claim 1 have a high accuracy for predicting tumor recurrence and tables 9, 13, and 17 of the disclosure show that the component profiles (a), (b), and (c) of independent claim 9 have a high accuracy for predicting one or more late effects. In other words, while the recited components of the profiles are known in the art of monitoring cancer patients, none of the cited prior art discloses the specific component panels recited in the instant claims or could predict the success of these component panels at predicting increased risk of tumor recurrence or one more late effects (see MPEP 716.02).
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 1-18 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more.
Independent claim 1 is directed toward a process which is one of the four statutory categories of invention. See MPEP 2106.03 I.
Claim 1 recites the limitation “wherein the subject’s level of each component in a component profile from a sample of the subject is not altered compared to a normal level of each component” or, in other words, comparing the subject’s level of particular components to reference levels, which under its broadest reasonable interpretation can be performed in the mind. Therefore, this limitation of the claim falls under the Mental processes grouping of abstract ideas as the claim recites obtaining data and thinking about the results (see MPEP 2106.04(a)(2)(III) and therefore recites a judicial exception. The specific biomarkers themselves fall under the natural phenomena category of abstract ideas and thus recites a judicial exception. These judicial exceptions are not integrated into a practical application because, although radiation therapy is being applied, in this context radiation therapy is extremely generalized and would generally be linking the abstract idea to the field of endeavor. See MPEP 2106.05(h). Furthermore, there is nothing particular about this treatment to the identified “not at an increased risk of tumor recurrence” (see MPEP 2106.04(d)(2)). Claims 3-8 and 17-18 fail to provide additional steps that would integrate the judicial exception into a practical application. The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the step of administering radiation therapy is considered well-understood, routine, and conventional in the art as evidenced by primary reference Mills (see rejection below). See MPEP 2106.05 I. A.
Claims 3-8 and 17-18 are directed toward naturally occurring components (i.e., natural phenomena or products of nature) and therefore, recite a judicial exception. See MPEP 2106.04. These claims fail to integrate the judicial exceptions into a practical application. These claims are merely qualifying the judicial exceptions and fail to recite additional steps that would integrate the judicial exceptions into a practical application. In other words, nothing is being done to the judicial exceptions themselves in a meaningful way beyond generally linking the judicial exceptions to radiation therapy. See MPEP 2106.04(d). These claims do not include additional elements that amount to significantly more because the claims fail the “machine or transformation” test. In other words, the judicial exceptions, the components of the component profile, are neither being used in a specific machine or transformed in some meaningful way. See MPEP 2106.05(b).
Therefore, claims 1, 3-8, and 17-18 are not patent eligible.
Independent claim 9 is directed toward a process which is one of the four statutory categories of invention. See MPEP 2106.03 I.
Claim 9 recites the limitation “wherein the subject’s level of each component in a component profile from a sample of the subject is not altered compared to a normal level of each component” or, in other words, comparing the subject’s level of particular components to reference levels, which under its broadest reasonable interpretation can be performed in the mind. Therefore, this limitation of the claim falls under the Mental processes grouping of abstract ideas as the claim recites obtaining data and thinking about the results (see MPEP 2106.04(a)(2)(III) and therefore recites a judicial exception. The specific biomarkers themselves fall under the natural phenomena category of abstract ideas and thus recites a judicial exception. These judicial exceptions are not integrated into a practical application because, although radiation therapy is being applied, in this context radiation therapy is extremely generalized and would generally be linking the abstract idea to the field of endeavor. See MPEP 2106.05(h). Furthermore, there is nothing particular about this treatment to the identified “not at an increased risk of one or more late effects” (see MPEP 2106.04(d)(2)). Claims 10-18 fail to provide additional steps that would integrate the judicial exception into a practical application. The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the step of administering radiation therapy is considered well-understood, routine, and conventional in the art as evidenced by primary reference Mills (see rejection below). See MPEP 2106.05 I. A.
Claims 12-16 are directed toward naturally occurring components (i.e., natural phenomena or products of nature) and therefore, recite a judicial exception. See MPEP 2106.04. These claims fail to integrate the judicial exceptions into a practical application. Claims 12-16 are merely qualifying the judicial exceptions and fail to recite additional steps that would integrate the judicial exceptions into a practical application because the invention is based on merely correlating the judicial exceptions to radiation therapy in a patient without adverse reaction risk. In other words, nothing is being done to the judicial exceptions themselves in a meaningful way beyond generally linking the judicial exceptions to radiation therapy adverse reaction risk. See MPEP 2106.04(d). These claims do not include additional elements that amount to significantly more because the claims fail the “machine or transformation” test. In other words, the judicial exceptions, the components of the component profile, are neither being used in a specific machine or transformed in some meaningful way. See MPEP 2106.05(b).
Therefore, claims 9-16 are not patent eligible.
CLAIM INTERPRETATION 2:
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 9 and 11-16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by United States Patent Application Publication US 2016/0160287 to Lambin et al. (herein Lambin).
Regarding claim 9, Lambin discloses using mitochondrial DNA variation (i.e., component profile) in cancer patients to successfully predict whether a subject will develop radiation-induced toxicity (i.e., adverse reaction) after ionizing radiotherapy. Incorporation of the mtDNA information in personalized radiation therapy planning might eventually allow for escalating doses in patients predicted to be at low risk for radiation induced toxicity, improving their chance of disease free survival (see [0008-0013]). In other words, Lambin discloses determining a cancer patient’s risk of an adverse reaction to radiation therapy and administering radiation therapy if said patient’s risk is considered low which reads on the limitations of the claim. Radiation-induced toxicity after ionizing radiotherapy reads on “one or more late effects” as recited in the instant claim. In regards to the limitation, “wherein the subject’s level of each component in a component profile from a sample of the subject is not altered as compared to a normal level of each component, wherein the component profile is selected from the following: (a) metanephrine, tryptophan, xanthurenic acid, and pantothenate; or (b) LPA 18:0, DAG 16:0/18:1, LPA 16:0, and DAG 18:1/18:1; or (c) metanephrine, tryptophan, xanthurenic acid, pantothenate, LPA 18:0, DAG 16:0/18:1, LPA 16:0, and DAG 18:1/18:1”, the MPEP states “the broadest reasonable interpretation of a method (or process) claim having contingent limitations requires only those steps that must be performed and does not include steps that are not required to be performed because the condition(s) precedent are not met” (see MPEP 2111.04). In other words, because the claimed invention (i.e., administering radiation therapy to a subject who has cancer and who is not at an increased risk of one or more late effects) can be practiced without the condition happening (i.e., the subject’s level of each component in a component profile, as outlined above, not being altered as compared to a normal level of each component), then the contingent wherein clause is not required under the broadest reasonable interpretation. Therefore Lambin discloses all the limitations of claim 9 above as it teaches administering radiation therapy to a subject with cancer who is not at increased risk of one or more late effects.
Regarding claims 11-16, the limitations of these claims are directed toward further qualifiers for the wherein clause claiming a condition of the subject to be treated with radiation therapy as discussed in regards to claim 9 and therefore fail to further limit the scope of independent claim 9.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 1, 3-8, and 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over United States Patent Application Publication US 2016/0160287 to Lambin et al. (herein Lambin) in view of United States Patent US 11,686,731 to Mills et al. (herein Mills) with a priority date PCT date 05 Jan 2016.
Regarding claim 1, Lambin discloses using mitochondrial DNA variation (i.e., component profile) in cancer patients to successfully predict whether a subject will develop radiation-induced toxicity (i.e., adverse reaction) after ionizing radiotherapy. Incorporation of the mtDNA information in personalized radiation therapy planning might eventually allow for escalating doses in patients predicted to be at low risk for radiation induced toxicity, improving their chance of disease free survival (see [0008-0013]). In other words, Lambin discloses determining a cancer patient’s risk of an adverse reaction to radiation therapy and administering radiation therapy if said patient’s risk is considered low which reads on the limitations of the claim. In regards to the limitation “wherein the subject’s level of each component in a component profile from a sample of the subject is not altered as compared to a normal level of each component, wherein the component profile is selected from the following: (a) geranyl pyrophosphate, glucose-1-phosphate, and 3 hydroxy-3-methylglutaryl-CoA; or (b) LPA 18:0, LPA 16:0, LPC 20:2, CER 24:0, and LPI 16:1; or (c) geranyl pyrophosphate, glucose-1-phosphate, 3 hydroxy-3-methylglutaryl-CoA, LPA 18:0, LPA 16:0, LPC 20:2, CER 24:0, and LPI 16:1”, the MPEP states “the broadest reasonable interpretation of a method (or process) claim having contingent limitations requires only those steps that must be performed and does not include steps that are not required to be performed because the condition(s) precedent are not met” (see MPEP 2111.04). In other words, because the claimed invention (i.e., administering radiation therapy to a subject who has cancer and who is not at an increased risk of tumor recurrence) can be practiced without the condition happening (i.e., the subject’s level of each component in a component profile, as outlined above, not being altered as compared to a normal level of each component), then the contingent wherein clause is not required under the broadest reasonable interpretation. Therefore Lambin discloses all the limitations of claim 1 above, except for “wherein the adverse reaction is tumor recurrence” as it teaches administering radiation therapy to a subject who is not at increased risk of an adverse reaction.
Mills discloses a method for providing prognosis for a subject with prostate cancer, or selecting a subject with prostate cancer for treatment with a particular therapy, comprising: (a) detecting the level of LRG1 polypeptide in a sample from a subject using an in vitro assay and (b) comparing the level of LRG1 polypeptide to a reference level of LRG1 polypeptide wherein an altered amount is an indication that a subject is likely to respond favorably to a particular treatment. In some cases elevated amounts of LGR1 polypeptide in the biological sample compared to the reference level are indicative of an increased risk of disease recurrence (i.e., tumor recurrence) in the subject following treatment with surgery or radiotherapy (see Cols. 2-3, Summary of Invention & Col. 8, lines 34-52)).
Mills and Lambin are analogous in the field of treating cancer patients with radiation. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date for the adverse reaction of the method of Lambin to be tumor recurrence for the benefit of adjusting therapy to combat increased risk of tumor recurrence (see Col. 3 lines 1-30 of Mills).
Regarding claims 3-8, the limitations of these claims are directed toward further qualifiers for the claimed component profile of a patient who does not have an increased risk of an adverse event and therefore fail to further limit the scope of independent claim 1.
Regarding claim 17, Lambin discloses all the limitations of claim 1. Lambin discloses wherein the normal level (number of variants) of the component, in this case mtDNA, comprises the subject’s level (number of variants) of the component prior to receiving radiation treatment for cancer (see [0008-0010]).
Regarding claim 18, Lambin discloses all the limitations of claim 1. Lambin discloses wherein the normal level of the component comprises a level generated from a population of individuals that did not have an adverse reaction after receiving radiation treatment for cancer (see [0027-0030]).
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over United States Patent Application Publication US 2016/0160287 to Lambin et al. (herein Lambin) in view of International Publication WO 2011/006214 to Sprung et al. (herein Sprung).
Regarding claim 10, Lambin discloses all the limitations of claim 9 above.
Lambin fails to disclose “wherein the late effects comprise rectal toxicity, urinary toxicity, or a combination thereof” as recited in the instant claim.
Sprung discloses that rectal and bladder (i.e., urine) toxicity are common side effects to radiation therapy (see pg. 4, lines 15-19).
Sprung and Lambin are analogous in the field of treating cancer patients with radiation. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date to determine if a patient is at increased risk for rectal or urinary toxicity for the benefit of recommending an alternative treatment regime (see pg. 1, lines 12-16 of Sprung).
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHRYN E LIMBAUGH whose telephone number is (571)272-0787. The examiner can normally be reached Monday-Thursday 7:00-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander can be reached at (571) 272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KATHRYN ELIZABETH LIMBAUGH/Primary Examiner, Art Unit 1797