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 .
Claim Status
Claim listing filed on November 12, 2025 is pending. Claims 3-4, 6, 21-22, and 24 are canceled. Claims 1 and 19 are amended. Claims 8-15, 17-18, and 26-33 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected species in the election made without traverse in the reply filed on October 23, 2024. Claims 1-2, 5, 7, 16, 19-20, 23, 25, and 34 are examined upon their merits.
Claim Rejections - 35 USC § 103 (Maintained)
The rejection of Claims 1-2, 5, 7, 16, 19-20, 23, 25, and 34 under 35 U.S.C. 103 as being unpatentable over Chou et al. PGPub US 2020/0155536 A1 (of record) in view of Ranganathan et al. Am J Pathol. 2003 (of record) is maintained.
Applicant's arguments filed November 12, 2025 have been fully considered but they are not persuasive.
Applicant argues that there is no guidance in the cited art that would lead the skilled artisan to combine and integrate the cited references to arrive at the claimed invention with an expectation of success. As of record in the non-final office action filed 08/12/2025, overexpression of CDK4 is taught by Ranganathan to be characteristic of ALS and there is motivation to incorporate differential CDK4 gene expression into the method of treatment taught by Chou to better identify patients with ALS who could benefit from treatment (motivation emphasized). It would be obvious to the skilled artisan to identify ALS patients by R155H p97 mutation and differential CDK4 expression as they were both known ALS biomarkers prior to the effective filing date. Further, it would be obvious to treat the identified ALS patients with p97 inhibitor CB-5083 as this inhibitor was a known treatment in this disease context prior to the effective filing date.
Applicant argues that Ranganathan fails to provide any teaching or guidance on identification of subjects having a motor neuron disease or symptom thereof. As of record in the non-final office action filed 08/12/2025, Ranganathan teaches that expression levels from samples across 10 ALS patients were compared to expression levels across 5 age-matched control patients and cyclin D1, CDK4, ppRb, and E2F1 were all overexpressed in the ALS patients as compared to the control patients (Table 2; of record). The data supports a model in which the RB1/E2F1 pathway is upregulated in ALS which stimulates motor neuron cell death (Figure 6 and page 833, paragraph 3; of record). It would be obvious to one of ordinary skill that these teachings define upregulated CDK4 as a biomarker of ALS, and identifying patients with a known biomarker of disease is standard practice in the art.
Applicant argues that neither Chou or Ranganathan teach or suggest the linkage of p97 mutation and differential expression of one or more genes in the RB1/E2F1 pathway as described in the amended claims. Specifically, Claim 1 recites “wherein the subject having at least one mutation in p97 expresses one or more genes involved in the RB1/E2F1 pathway differently than in a normal subject caused by at least one mutation in p97.” Claim 19 similarly recites “wherein the subject in need has a mutant p97 and expresses one or more genes involved in the RB1/E2F1 pathway differently than in a normal subject caused by the mutant p97.” It is of record in the non-final office action filed 08/12/2025 that if the differential gene expression were interpreted to be caused by the mutation in p97, the differential gene expression limitation would be considered an inherent functional property of mutant p97 (see MPEP § 2112). Examiner maintains this interpretation because, as stated by Applicant in the remarks filed 11/12/25 (page 7, last paragraph), the alteration of the RB1/E2F1 pathway is a natural result of at least one mutation in p97. A rejection under 35 U.S.C. 103 can be made when the prior art seems to be identical except that the prior art is silent as to an inherent characteristic (MPEP § 2112.III). For example, MPEP § 2112.02.I recites “In re King, 801 F.2d 1324, 231 USPQ 136 (Fed. Cir. 1986) (The claims were directed to a method of enhancing color effects produced by ambient light through a process of absorption and reflection of the light off a coated substrate. A prior art reference to Donley disclosed a glass substrate coated with silver and metal oxide 200-800 angstroms thick. While Donley disclosed using the coated substrate to produce architectural colors, the absorption and reflection mechanisms of the claimed process were not disclosed. However, King’s specification disclosed using a coated substrate of Donley’s structure for use in his process. The Federal Circuit upheld the Board’s finding that ‘Donley inherently performs the function disclosed in the method claims on appeal when that device is used in ‘normal and usual operation’’ and found that a prima facie case of anticipation was made out. Id. at 138, 801 F.2d at 1326” (emphasis added). In the instant scenario, Chou teaches administering CB-5083 to ALS patients comprising a p97 mutation. Although Chou does not disclose that a p97 mutation mechanistically causes differential RB1/E2F1 gene expression, the ALS patients taught by Chou inherently have this characteristic because they possess the causal p97 gene mutation. MPEP § 2112.02.I teaches a second applicable example: “The Board rejected a claim directed to a method for protecting a plant from plant pathogenic nematodes by inoculating the plant with a nematode inhibiting strain of P. cepacia. A U.S. patent to Dart disclosed inoculation using P. cepacia type Wisconsin 526 bacteria for protecting the plant from fungal disease. Dart was silent as to nematode inhibition but the Board concluded that nematode inhibition was an inherent property of the bacteria” (emphasis added). Thus, based on the examples of inherency taught by MPEP § 2112, Examiner maintains that the differential gene expression limitation is an inherent functional property of mutant p97 and is obvious over the cited art.
Applicant argues that the non-final office action has not met its burden to show by evidence or technical reasoning that alteration of RB1/E2F1 pathway in a subject having a motor neuron disease or symptom thereof naturally flows from a result of at least one mutation in p97. Examiner maintains that the RB1/E2F1 differential gene expression caused by at least one mutation in p97 does not change the methodological steps of a method of improving, ameliorating, or relieving a motor neuron disease that are obvious over Chou in view of Ranganathan. Regardless of whether or not the RB1/E2F1 differential gene expression is caused by a p97 mutation, the method still comprises identifying patients with a p97 mutation and RB1/E2F1 differential gene expression and administering a p97 inhibitor. MPEP § 2112.I states “’[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.’ Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable” (emphasis added). In the instant scenario, a p97 mutation causing RB1/E2F1 differential gene expression is a scientific explanation for the prior art’s functioning that was inherently present in the prior art. Chou teaches administering CB-5083 to patients comprising a p97 mutation, and if the p97 mutation causes RB1/E2F1 differential gene expression, then these patients also had this characteristic even though it was not explicitly stated. The mechanistic explanation that a p97 mutation causes RB1/E2F1 differential gene expression does not change the fact that identifying ALS patients by a p97 mutation and RB1/E2F1 differential gene expression and treating them with a p97 inhibitor was obvious over the cited art prior to the time of filing. Applicant’s arguments have been considered but are not persuasive.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. 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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/SARAH COOPER PATTERSON/Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675