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 .
Response to Amendment
The preliminary amendment filed on May 22, 2025 is acknowledged. The application will be examined accordingly.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on March 14, 2024 is being considered by the examiner.
Claim Objections
Claims 1, 47 and 68 are objected to because of the following informalities:
In claim 1, a comma is missing after “(NF-L)”.
In claim 47, the limitation “therapy” should be changed to “a therapy”.
In claim 68, the limitation “the patent” is misspelled”.
Appropriate corrections are required.
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 15-18, 23, 47-49, 65, 68 and 86 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more.
With respect to independent claims 15 and 65, the claims recite a step of diagnosing a patient with a medical condition based on biomarkers present in the patient. This is dictated by laws of nature, which is considered a judicial exception. That said, the judicial exception is not integrated into a practical application so as to obviate a rejection under 35 U.S.C. 101. While claims 15 and 65 recite a step of administering ALS therapy to the patient based on the diagnosis, the nature of the therapy is too generic to constitute a practical application*. See MPEP 2106.04(d)(2). In addition, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception so as to obviate the rejection. Step b) constitutes an additional element apart from the judicial exception, but it is not “significantly more than the judicial exception” because generically administering ALS therapy to a patient is well-known in the art (see [0005] of Ajami et al. US 2018/0346577 A1).
The dependent claims identified in the heading are rejected because they do not cure the deficiencies of claims 15 and 65.
*Claims 21, 67, 82-85 are not rejected under 35 U.S.C. 101 because they recite particular treatments, which constitute a practical application of the judicial exception.
Likewise, independent claim 47 is rejected. Like claims 15 and 65, claim 47 recites a step of diagnosing a medical condition based on biomarkers present in the body, which is dictated by laws of nature. In addition, the judicial exception is not integrated into a practical application so as to obviate a rejection under 35 U.S.C. 101 because the claim terminates with the judicial exception (i.e. nothing is done with the judicial exception). While the claim further recites a step of administering the therapy prior to making the determination (i.e. step a), the administration of the therapy is considered an insignificant extra-solution activity relative to the judicial exception, and thus this step is not considered as a step that integrates the judicial exception into a practical application. Moreover, step a) does not constitute additional elements that are sufficient to amount to significantly more than the judicial exception so as to obviate the rejection because this step is well-known (see citation to Ajami above).
The dependent claims are rejected because they do not cure the deficiencies of claim 47. While claim 48 does do something with the judicial exception, as discussed above, a generic therapy does not constitute a practical application.
Claim Rejections - 35 USC § 112
In the event the determination of the status of the application as subject to AIA (or as subject to pre-AIA ) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the rationale supporting the rejection would be the same under either status.
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.
Claims 16, 17, 23, 29, 35, 47-49, 65, 67, 68, and 82-85 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 16 is indefinite because it recites a verb in passive voice (“is determined”). It is unclear whether the claim intends the verb to refer to a method step of the present claimed invention, or whether it intends to merely provide context. If the claim intends the verb to refer to a method step, then the verb should be recited in active voice (“further comprising determining”).
Likewise, claims 23 and 35 are indefinite. It is unclear whether the claim intends to recite a step of collecting the serum sample.
Claims 17 and 29 recite a single reference concentration value for at least two serum immune-based biomarkers. It is unclear whether the claims intend to recite the use of a single reference value for multiple biomarkers. Based on the recitation of “its reference concentration” in claim 17, it appears that each biomarker comprises its own reference concentration. If so, the claims should be amended accordingly.
Claims 47 and 65 recite a Markush group of biomarkers. A Markush group should be a closed list (e.g. see claim 15 reciting “is” rather than “comprises”). Consequently, a list reciting “comprises” renders the scope of the Markush group indefinite.
Relatedly, claim 86 expands the Markush group. Because a Markush group consists of a closed list, a dependent claim cannot expand the list.
Claims 83 and 85 recite “the first and/or second ALS therapy”. There is no antecedent basis for the limitation.
Claim 85 recites “e.g.” Such recitation renders the claim indefinite. See MPEP § 2173.05(d).
Claims not explicitly rejected are rejected due to dependency.
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 27, 29, 35 and 39 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Blennow et al. (“Blennow”) (US 2019/0277864 A1).
With respect to claim 27, the scope of the claim consists of administering an ALS therapy to a patient diagnosed with ALS. The claimed method does not include measuring the concentration of a biomarker, or even comparing biomarker concentration to a reference value. The limitations directed to the biomarker merely identify the bio-composition of the patient. In this case, the claimed biomarkers are present in a patient diagnosed with ALS, and the claim does not specify the reference concentration, meaning the concentration of the at least one biomarker can be any value. Consequently, prior art teaching a method of administering a therapy to any patient diagnosed with ALS is sufficient to anticipate the claim.
That said, Blennow discloses a method of administering an ALS therapy to a patient diagnosed with ALS (see [0158]).
With respect to claim 29, as discussed above (see rejection of claim 27), the claimed method consists of administering an ALS therapy to a patient diagnosed with ALS. It does not include a step of comparing the concentration(s) of biomarker(s) with reference concentration(s). That said, the disclosure of [0158] is sufficient to anticipate claim 29 as well.
With respect to claim 35, as discussed above, the claimed method consists of administering an ALS therapy to a patient diagnosed with ALS. It does not include a step of analyzing the serum sample, let alone collecting the serum sample. Consequently, prior art need not teach the claimed serum sample to reject claim 35. Nevertheless, Blennow teaches analyzing a serum sample from the patient prior to administering the therapy (see [0158]) and [0015]).
With respect to claim 39, as discussed above, the claimed method consists of administering an ALS therapy to a patient diagnosed with ALS. It does not include a step of comparing the concentration of the at least one biomarker to the reference concentration. Consequently, prior art need not teach the origin of the reference concentration to reject claim 39.
Claims 27, 29, 33, 35 and 39 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tang et al. (“Tang”) (WO 2020/223568 A1).
With respect to claim 27, Tang discloses a method of administering an ALS therapy to a patient diagnosed with ALS (see claims 12-13).
With respect to claims 29, 35 and 39, as discussed above (see rejection based on Blennow), the claimed method consists of administering an ALS therapy to a patient diagnosed with ALS. Consequently, prior art need not teach the claimed serum sample or the origin of the reference concentration to reject the claims
With respect to claim 33, the treatment/therapy comprises Treg infusion (see embodiments 12-14, p. 10-11).
Claims 47 and 49 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bowser (US 8,465,727 B2).
With respect to claim 47, Bowser discloses a method of monitoring efficacy of a therapy to treat ALS, the method comprising:
a) administering an ALS therapy to a patient diagnosed with ALS (see claim 18), and
b) determining whether a concentration of at least one serum immune-based biomarker in a serum sample (see lines 18-25, col. 6) collected from the patient after the therapy is less than, equal to, or greater than, a reference concentration (i.e. concentration of the at least one biomarker pre-therapy), wherein the at least one serum immune-based biomarker comprises C reactive protein (CRP) (see abstract),
wherein the ALS therapy is deemed to have poor efficacy if the concentration of the at least one serum immune-based biomarker is greater than its reference concentration (see [0088] disclosing that the therapy is intended to lower the biomarker concentration).
With respect to claim 49, the efficacy of the therapy is based on whether the concentration of the at least one biomarker decreases after the therapy (see claim 18). Naturally, the origin of the reference concentration is a serum sample obtained from the patient prior to the therapy.
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.
Claim 48 is rejected under 35 U.S.C. 103 as being unpatentable over Bowser.
With respect to claim 48, given that the concentration of the at least one biomarker is indicative of the progression of ALS (see abstract), and hence the efficacy of the treatment, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have continued a second round of the therapy if the concentration of the at least one biomarker is less than the reference concentration (i.e. the therapy is effective).
Claims 15, 16, 18 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Blennow in view of Bowser.
With respect to claim 15, Blennow discloses a method for selecting a patient for an ALS therapy (see [0099] and [0023), the method comprising:
comparing a concentration of at least one biomarker in a serum sample collected from a patient diagnosed with or suspected of having ALS with a reference concentration (see [0001]), wherein the at least one biomarker is neurofilament-light (NF-L) (see [0001]); and
administering the ALS therapy to the patient (see [0139]).
The method differs from the claimed invention in that Blennow does not disclose that the patient is selected for the therapy based on the concentration of the at least one biomarker being less than or equal to the reference concentration.
Bowser discloses a method of assessing the efficacy of an ALS treatment (see [0088]), the method comprising the steps of determining the concentration of a biomarker in a serum sample (see [0038]) of a patient, and comparing the concentration to the concentration of the biomarker from a sample obtained pre-treatment to see if the treatment is effective (see [0088]). In light of the disclosure of Bowser, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used the biomarker concentration from the patient’s serum obtained pre-treatment as the reference concentration in the Blennow method to determine whether the treatment is effective. If the modification is made, then step b) of Blennow’s method would comprise selecting the patient for treatment (i.e. continue treatment) if the concentration of the at least one biomarker is less than the reference concentration.
With respect to claim 16, to perform the method of claim 15, it is evident that the concentration of the at least one biomarker is determined.
With respect to claim 18, as discussed above (see rejection of claim 15), the reference concentration would be obtained from a serum sample obtained from the patient prior to the therapy.
With respect to claim 23, based on the language of claim 15 (the therapy is administered to the “selected” patient, which can only occur after conducting step a), it is evident that the serum sample is collected and analyzed prior to step b).
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Blennow in view of Bowser as applied to claims 15, 16, 18 and 23 above, and further in view of Axtell et al. (“Axtell”) (US 2011/0243893 A1).
The combination of Blennow and Bowser does not disclose determining the concentration of at least two biomarkers. However, there are biomarkers other than NF-L known to be useful for predicting the responsiveness of a patient to ALS treatment, for example IL-17F (see claim 4 of Axtell). In light of the disclosure of Axtell, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have also determined the concentration of IL-17F in the serum sample and compared that to its reference concentration to determine whether the treatment is effective. The modification would provide a more complete analysis of whether the treatment is effective.
Claim 21 are rejected under 35 U.S.C. 103 as being unpatentable over Blennow in view of Bowser as applied to claims 15, 16, 18 and 23 above, and further in view of Tang.
With respect to claim 33, because the disclosure of Blennow is broadly directed to neurodegenerative diseases (as opposed to specifically ALS), Blennow does not explicitly disclose the claimed ALS-specific treatments. Nevertheless, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used the modified method to determine the efficacy of any conventional ALS treatment/therapy, including Treg infusion (see embodiments 12-14, p. 10-11, of Tang disclosing that Treg infusion is a well-known ALS treatment).
Claims 65, 67, 68, 82 and 85 are rejected under 35 U.S.C. 103 as being unpatentable over Blennow in view of Bowser, Tang and Axtell.
With respect to claim 65, as discussed above, the combination of Blennow, Bowser, Tang and Axtell teaches a method of determining the efficacy of Treg therapy based on comparing the concentration of IL-17F post-therapy to the concentration of IL-17F pre-therapy (reference concentration). Naturally, if the concentration of IL-17F is lower than the reference concentration, signaling that the therapy is effective, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have continued the therapy.
With respect to claim 67, Bowser further discloses that CRP is a known biomarker for ALS (see line 29, col. 7). In light of the disclosure of Bowser, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have also determined the concentration of CRP in the serum sample and compared that to its reference concentration to determine whether the treatment is effective. The modification would provide a more complete analysis of whether the treatment is effective.
With respect to claim 68, as discussed above (see rejection of claim 65), the reference concentration would be obtained from a serum sample obtained from the patient prior to the therapy.
With respect to claim 82, as discussed above, step b) would comprise continuing the Treg therapy.
With respect to claim 85, via infusion of Treg, it is evident that Treg exosomes are also infused.
Claims 83 and 84 are rejected under 35 U.S.C. 103 as being unpatentable over Blennow in view of Bowser, Tang and Axtell as applied to claims 65, 67, 68, 82 and 85 above, and further in view of Perrin et al. (“Perrin”) (US 2011/0293612 A1).
With respect to claims 83 and 84, the combination of Blennow, Bowser, Tang and Axtell does not disclose abatacept as a treatment for ALS.
Perrin discloses a therapeutic cocktail comprising abatacept (see [0042]), and further discloses that abatacept can be administered with other therapeutic compounds (see [0042]). Based on the stage/progression of ALS, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have administered a combination of Treg and abatacept before step a). Naturally, step b), which constitutes continuation of the therapy, would comprise a step of administering abatacept to the patient.
Claim 86 is rejected under 35 U.S.C. 103 as being unpatentable over Blennow in view of Bowser, Tang and Axtell as applied to claims 65, 67, 68, 82 and 85 above, and further in view of Hosaka et al. (“Hosaka”) “Biomolecular Modifications Linked to Oxidative Stress in Amyotrophic Lateral Sclerosis: Determining Promising Biomarkers Related to Oxidative Stress”.
With respect to claim 86, the combination of Blennow, Bowser, Tang and Axtell does not disclose using ox-LDL or 4-HNE as a biomarker. However, as discussed above (see rejection of claim 67), it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have also determined the concentrations of additional biomarkers in the serum sample and compared them to their respective reference concentrations to determine whether the treatment is effective. That said, Hosaka discloses that 4-HNE is a biomarker for determining the progression of ALS (see section 4.1, p. 9).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL S HYUN whose telephone number is (571)272-8559. The examiner can normally be reached M-F 8:30-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Luan Van can be reached at 571-272-8521. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL S HYUN/Primary Examiner, Art Unit 1796
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