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 with traverse of species of a) a method of treating a patient with MS and b) diroximel fumarate in the reply filed on 12/16/2025 is acknowledged. The traversal is on the grounds that there is no undue burden. This is not found persuasive because the instant applicant is being examiner under 371 and undue burden is not one of the consideration but rather lack of unit which was established in the restriction. It is noted that the species requirement towards drug treatments is withdrawn upon further consideration.
The requirement is still deemed proper and is therefore made FINAL.
Claims 6-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 12/16/2026.
Claims 1-5 are under consideration in the instant Office Action.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Objections
Claim 1 is objected to because of the following informalities: Claim 1 calls for “…an long-term stable…” at the end of the claim. It should read “…a long-term stable…”. Appropriate correction is 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 1-5 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural correlation without significantly more. The claims recite a method treating MS by obtaining a hematopoietic cell sample from a patient with relapsing MS, determining the number of CD19+, CD24+ and CD38+ transitional B cells, expression level of neurofilament light (NFL) and inflammatory marker and then treating the subject with one of the listed treatments only when the patient has a decreased number of CD19⁺, CD24⁺, CD38⁺ transitional B cells, and an increase in NFL inflammatory marker relative to an untreated MS control sample, an unresponsive MS control
sample, or a long-term stable disease sample. This judicial exception is not integrated into a practical application because the method relies on the detection of the levels of naturally occurring biomarkers of MS. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because they rely on using the levels of naturally occurring and only apply the treatment if the levels are met, but the method still relies on the natural correlation to “apply it” since there is no narrow, specific treatment but all of the possible treatments for MS. The method is solely directed to performing the steps to determine the natural correlation in the patient population and then to “apply it.” Moreover, a claimed treatment step or agent must be “particular”, i.e., specifically identified, so that it does not encompass all applications of a judicial exception(s) in order to integrate it into a practical application. The instant treatment limitation is not considered a “particular” treatment and is instead considered merely instructions to apply the judicial exception or is merely indicating a field of use. See MPEP § 2106.05(h).
The subject matter eligibility under 35 U.S.C. 101 of natural products (i.e., whether the claimed product is a non-naturally occurring product of human ingenuity that is markedly different from naturally occurring products) was confirmed by the U.S. Supreme Court decisions including Association for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. _, 133 S. Ct. 2107, 2116, 106 USPQ2d 1972 (2013), and Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. _, 132 S. Ct. 1289, 101 USPQ2d 1961 (2012). "[L]aws of nature, natural phenomena, and abstract ideas" are not patentable. Diamond v. Diehr, 450 U. S. 175, 185 (1981); see also Bilski v. Kappos, 561 U. S. __, __ (2010) (slip op., at 5). "Phenomena 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." Gottschalkv. Benson, 409 U. S. 63, 67 (1972).
In Prometheus, the Court found that "[i]f a law of nature is not patentable, neither is a process reciting a law of nature, unless that process has additional features that provide practical assurance that the process is more than a drafting effort designed to monopolize the law of nature itself." Additionally, "conventional or obvious" "[pre]solution activity" is normally not sufficient to transform an unpatentable law of nature into a patent-eligible application of such a law". Flook, 437 U. S., at 590; see also Bilski, 561 U. S., at __ (slip op., at 14) ("[T]he prohibition against patenting abstract ideas 'cannot be circumvented by’..., adding 'insignificant post-solution activity'" (quoting Diehr, supra, at 191-192)).
The Court also summarized their holding by stating "[t]o put the matter more succinctly, the claims inform a relevant audience about certain laws of nature; any additional steps consist of well understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately."
Thus, if the claim recites or involves a judicial exception, such as a law of nature/natural principle or natural phenomenon (e.g., the law of gravity, F=ma, sunlight, barometric pressure, etc.), and/or something that appears to be a natural product (e.g., a citrus fruit, uranium metal, nucleic acid, protein, etc.), then the claim only qualifies as eligible subject matter if the claim as a whole recites something significantly different than the judicial exception itself.
In the instant case, based upon an analysis with respect to the claim as a whole, claims 1-5 are determined to be directed to judicial exception without significantly more. The rationale for this determination is explained below in view of controlling legal precedent set forth in 2019 Revised Patent Subject Matter Eligibility Guidance (84 FR 50) dated January 07, 2019.
The instant claims 1-5 encompass a process. (Step 1: Yes).
Next, Step 2, is the two-part analysis from Alice Corp. (also called the Mayo test) to determine whether the claim is directed to laws of nature, natural phenomena, and abstract ideas (the judicially recognized exceptions). (In Alice Corp. v. CLS Bank Int’l, 134 S. Ct. 2347, 2354 (2014) the Supreme Court sets forth a two-step test for determining patent eligibility. First, determine if the claims encompass a judicial exception (a natural phenomenon/law of nature/abstract idea). If so, then ask whether the remaining elements/steps, either in isolation or combination with the other non-patent-ineligible elements, are sufficient to ‘“transform the nature of the claim’ into a patent-eligible application.” Id. at 2355 (quoting Mayo, 132 S. Ct. at 1297). Put another way, there must be a further “inventive concept” to take the claim into the realm of patent eligibility. Id. at 2355. In the recent Myriad v Ambry case, the CAFC found claims (drawn to methods comprising obtaining tissue samples, analyzing sequences of cDNA and comparing germline sequences of a gene to wild-type sequences) to encompass the abstract mental processes of ‘comparing’ and ‘analyzing’. Recitation of specific techniques (in Myriad claims 7 and 8 further recited hybridization and PCR) were deemed not “enough” to make the claims patent-eligible since the claims contained no otherwise new process. The elements/steps recited in addition to the judicial exception did nothing more than spell out what practitioners already knew). The instant claims encompass the determination of the levels of biomarkers that are indicative of MS in a subject, the process that is governed by a law of nature, and thus is a judicial exception. While the claims do not explicitly call for a diagnosis it still reads on a diagnostic method since it requires the samples from subjects suspected of MS. Thus, the relation between the biomarker levels are indicative of MS in principle and is a consequence of the ways these factors are metabolized by the body, entirely natural process, a natural phenomenon, and thus a judicial exception (Step 2A/1: Yes).
Next, prong two of Step 2A requires identifying whether there are additional elements recited in the claim beyond the judicial exception(s) and evaluating those additional elements to determine whether they integrate the exception into a practical application of the exception. “Integration in to a practical application” requires an additional element or combination of additional elements in the claim to apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception, such as the claim is more than a drafting effort designed to monopolize the exception. In the instant case, the independent claims do not recite any additional elements to integrate the judicial exception into a practical application because all the steps of the claimed methods are limited to only those that measure naturally occurring biomarkers that are indicative of MS. Claim 1 sets forth the step of “treat it” or “apply it” since it call for a generic type of treatment for MS to be pulled from a wide range of possible genera of treatments without any guidance of when and how to apply in view of the biomarkers expect that if they are detected in the subject at an increased level that are detected in the instant method that requires the natural correlation. (Step 2A/2: No). The second step is determining if the claims recite or involve judicial exceptions, such as laws of nature, natural phenomena, or natural products. In this case, the claims involve a natural correlation: biomarker levels associated with MS subjects that are indicative MS which is based on a natural correlation. In the next step, it must be determined if the claim as a whole amounts to something significantly more than the judicial exception. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. Claims 1-5 fail to include any limitations which would distinguish the method because they do not recite any elements, or combinations of elements to ensure that the claim as a whole amounts to significantly more than the judicial exception because the active steps of the claims – collecting biological samples, determining the levels of the biomarkers in the samples and determining the difference in the levels of naturally occurring biomarkers − represent routine steps that are recited at a high level of generality and encompass well-understood and purely conventional routine techniques in the art, as shown by the prior art which show that the methods of monitoring MS are well known in the art. The instant claims only require the naturally occurring correlation to be observed by applying the known methods in the art. Claim 1 sets forth the step of “treat it” or “apply it” since it call for a generic type of treatment to be pulled from a wide range of possible genera of treatments without any guidance of when and how to apply in view of the biomarkers that are detected in the instant method that requires the natural correlation. For example, prior art shows that the methods of using flow cytometry to determine the levels of the CD19, CD24 and CD34 biomarkers that indicate MS as required in the instant claims was known in the prior art as evidenced by Schubert et al., US2016/0054320 (IDS 1/6/2023) and the NFL levels in MD as taught by Kuhle et al., 2019 (IDS 1/6/2023). The instantly rejected claims do not recite any elements in addition to the natural correlation that impose meaningful limits on the claim scope and would substantially foreclose others from using this natural correlation of the biomarkers that are indicative of MS without significantly more. The intended use of this method does not further limit or apply any significant action once the natural correlation has been observed using the claimed method. The natural correlation is found in nature whether it is observed or not and would be present and act quite independently of any effort of the patentee.
Note that the specific biomarkers that are indicative of MS do not add significantly more to satisfy step 2B (Step 2B: No).
Thus, for reasons fully explained above, claims 1-5 do not satisfy the requirement of 35 U.S.C. 101 and are therefore rejected.
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.
Claims 1-5 are rejected under 35 U.S.C. 103 as being unpatentable over Schubert et al., US2016/0054320 (IDS 1/6/2023) and Kuhle et al., 2019 (IDS 1/6/2023).
Schubert discloses a method of treating a patient with multiple sclerosis (MS) ([0007] [0008] and [0114]; relapsing-remitting multiple sclerosis (RRMS) patients), the method comprising: obtaining a hematopoietic cell sample, cells from bone marrow ([0023], [0053]), from a patient having MS, wherein the patient was in relapse for MS ( see [0007]) a sample comprising lymphocytes, which is drawn conveniently from the peripheral blood, and determining the number of CD19+, CD24+, CD38+ transitional B cells in the hematopoietic cell sample (see [0069] and claims 6-10) as in instant claims 1 and 3. Schubert teaches cytokines (inflammatory marker) of interest include IL-1b (see [0104]) and meets the requirements of instant claims 1-2 of an inflammatory biomarker. Schubert teaches that the treatments include copaxone, fingolimod, natalizumab, dimethyl fumarate, teriflunomoide and interferon beta (see [0007], [0015-16], [0044]) as required in instant claim 1. Schubert teaches cell count analysis using the makers CD19, CD24 and CD38 showing the distribution of B cell populations for a healthy control, and MS treated patients and teaches measuring these biomarkers in the context of determining the presence, absence, quantity, amount, or effective amount of a substance in a clinical or subject-derived sample, including the presence, absence, or concentration levels of such substances, and/or evaluating the values or categorization of a subjects clinical parameters based on a control. (see [0009], [0016], [0055]) as in instant claim 3. Schubert teaches the method of detection being flow cytometry (see [0007] and claim 11) as required in instant claim 4. Schubert teaches the subject as human (see [0024] and claim 12) as in instant claim 5. Schubert does not teach the required biomarker neurofilament light (NFL) of instant claim 1.
Kuhle teaches the NFL is a biomarker for MS disease. Kuhle teaches blood NFL levels are associated with clinical and MRI-related measures of disease activity and neuroaxonal damage and have prognostic value in MS patients (see abstract). Kuhle teaches NFL as a potential biomarker to monitor MS disease activity and treatment response using blood samples obtained in the course of 2 large, phase 3, randomized controlled clinical trials of fingolimod in relapsing-remitting MS (RRMS; see page e1008 first column) as in instant claim 1. Kuhle does not teach the other biomarkers of claim 1.
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of Schubert and Kuhle. The person of ordinary skill in the art would have been motivated to make and use the invention as claimed because the combination of multiple biomarkers improves the diagnostic potential of an assay. Both Schubert and Kuhle show that these biomarkers are effective biomarker in detecting RRMS which would motivate one of ordinary skill in the art to combine these known and effective biomarkers for the use in MS diagnosis. The person of ordinary skill in the art would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
Conclusion
No claims are allowed.
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/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675