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
The present Application, filed March 10, 2022, is a national stage entry of International Patent Application No. PCT/EP2021/055622, filed March 5, 2021, which claims priority to U.S. Provisional Patent Application No. 62/986,171, filed March 6, 2020.
Status of the Claims
In the amendment filed November 16, 2025, claims 4, 7, 15-17, 49, 52, 53, 57, and 60 are canceled, and new claims 65-72 are added. Claims 1-3, 5, 8, 50, 58, and 61. Claims 18-48 were previously canceled. Claims 1-3, 5-6, 8-14, 50-51, 54-56, 58-59, and 61-72 are currently pending, with claims 65-72 being withdrawn, as described below.
Election/Restrictions
Newly submitted claims 65-72 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: the method of claim 65 overlaps with the method of claim 1, but includes an additional step that is not present in the method of claim 1. Accordingly, the inventions claims 1 and 65 are related as combination and subcombination. Inventions in this relationship are distinct if it can be shown that (1) the combination as claimed does not require the particulars of the subcombination as claimed for patentability, and (2) that the subcombination has utility by itself or in other combinations (MPEP § 806.05(c)). In the instant case, the combination as claimed does not require the particulars of the subcombination as claimed because the method of claim 1 can be performed, as a complete method, without the additional step of discontinuing a previous standard of care treatment that does not include ponesimod. The subcombination has separate utility such as treating patients who have previously been subject to other treatments, as opposed to patients who are receiving ponesimod as their first treatment.
The examiner has required restriction between combination and subcombination inventions. Where applicant elects a subcombination, and claims thereto are subsequently found allowable, any claim(s) depending from or otherwise requiring all the limitations of the allowable subcombination will be examined for patentability in accordance with 37 CFR 1.104. See MPEP § 821.04(a). Applicant is advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 65-72 withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Previous Rejections and/or Objections
Any objections and/or rejections raised in the previous Office Action but not reiterated below are considered to have been withdrawn.
Claim Rejections - 35 USC § 112 – Necessitated by Amendment
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.
The following is a quotation of 35 U.S.C. § 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-3, 5-6, 8-14, 50-51, 54-56, 58-59, and 61-64 are indefinite:
Claims 1-3, 5-6, 8-14, 50-51, 54-56, 58-59, and 61-64 are rejected under 35 U.S.C. § 112(b) or 35 U.S.C. § 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Applicant arguments:
With respect to amended claims, Applicant argues that the phrase, “a standard of care treatment that does not include ponesimod is defined in the specification and thus one would have no difficulty understanding the metes and bounds of this limitation. This misunderstands the reasons for rejection for indefiniteness. As discussed below, and similar to the previous rejection of claim 1 for indefiniteness, this rejection results from the fact that, regardless of the clarity of what constitutes “a standard of care treatment that does not include ponesimod,” but relates moreso to the phrase, “is effective to.” In particular, it is not clear whether the recited efficacy outcome must be observed in the specific subject patient being treated, or whether it instead requires that the treatment be shown to typically, frequently, or at least occasionally be effective to achieve the recited outcome, such as by a clinical trial comparing a population of ponesimod-treated subjects to a population of non-ponesimod, standard-of-care-treated subjects. At least because of this uncertainty, claims 1 is indefinite.
Modified rejections:
Claim 1 is indefinite for reciting, “using a regimen that is effective to slow brain volume loss relative to a patient population having substantially similar baseline disease characteristics and receiving a standard of care treatment that does not comprise ponesimod,” because a person of ordinary skill in the art could not reasonably determine the metes and bounds of this limitation.
It would be unclear, for example, how it is to be determined whether the method “is effective to” slow brain loss relative to the recited patient population. In particular, it would be unclear whether it must be shown that the specific patient being treated For example, the limitation might require that a clinical study be performed that demonstrates some statistical diminishment in brain volume loss in a clinical treatment population, relative to an untreated population. If so, the claim fails to recite any study parameters or statistical certainty required to make such a characterization. Furthermore, the claim fails to indicate a magnitude of slowing, or a time frame in which it must be observed (according to the hypothetical study demonstrating such slowing). For at least these reasons, claim 1 is indefinite. Claims 2-3, 5-6, 8-14, 50-51, 54-56, 58-59, and 61 are indefinite for depending directly or indirectly from claim 1 without completely curing this indefiniteness.
Claim 3 is further indefinite for reciting, “wherein the standard of care treatment that does not comprise ponesimod is 14 mg of teriflunomide once daily,” because a person of ordinary skill in the art could not reasonably determine the metes and bounds of this limitation. This limitation is indefinite for essentially the same reasons as described with respect to claim 1, above. It is unclear how one would determine whether the regimen is effective to slow brain volume loss relative to a patient receiving 14 mg of teriflunomide once daily. For example, it would be unclear whether one would have to test this proposition in the specific subject being treated, to refer to a clinical trial showing that this is the case as a probabilistic matter, with some unstated threshold of frequency, or whether satisfaction of this element would be determined by some other means.
Claim Rejections - 35 USC § 103 – Modified in View of Amendment, Substantially Reiterated
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, 3, 5-6, 9, 14, and 58-59, and 62 are obvious over Olsson and Hoch:
Claim 1, 3, 5-6, 9, 14, and 57-62 are is rejected under 35 U.S.C. § 103 as being unpatentable over the non-patent publication, Oral ponesimod in relapsing–remitting multiple sclerosis: a randomised phase II trial, J. Neurol. Neurosurg. Psychiatry, 85, pgs. 1198-1208 (2014) by Olsson et al. (hereinafter, “Olsson”), in view of the non-patent publication, A Novel Gradual Up-Titration Regimen Mitigates The First-Dose Effects Of Ponesimod, A Selective S1p1 Receptor Modulator, Clinical Therapeutics, 37, pgs. e36-e37 (2015) by Hoch et al. (hereinafter, “Hoch”), a summary of a poster presentation.
Claim 1 is amended to incorporate the features of original claim 8. With respect to the previous rejections of claim 8 for obviousness, Applicant asserts that the previous Office Action suggests that Olsson does not describe an up-titration method (pg. 8 of Applicant’s Remarks of November 16, 2025, final paragraph). The Office Action makes no such suggestion. Regardless the point of Applicant’s assertion in this respect is that the fact that Olsson utilizes its own up-titration method would preclude one from utilizing the up-titration method of Hoch in combination with the ponesimod administration method of Olsson. This argument has been fully considered, but is not found persuasive.
This is an instance in which the combination of known elements according to known methods is obvious because it does no more than yield predictable results (KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398 (2007). As the court noted in KSR, “a patent for a combination which only unites old elements with no change in their respective functions…is obvious.” While the specific facts of KSR pertain to a mechanical product, the reasoning is equally applicable to the elements of a method. In the present case, the ponesimod administration operates to treat multiple sclerosis, as known from Olsson; and the up-titration operates to mitigate first-dose effects, as known from Hoch. The fact that Olsson was also aware of first-dose effects and utilized a somewhat different up-titration to combat them is irrelevant.
Further to that point, Applicant has asserted that, to set for a prima facie rejection over Olsson and Hoch, the Examiner must provide evidence that there was a recognized problem or need in the art (pg. 10 of Applicant’s Remarks, third full paragraph). By “problem,” Applicant appears to mean a recognition or belief that the up-titration of Olsson is ineffective. As a first matter, evidence that there was a recognized problem or need in the art is not a general requirement of a prima facie case of obviousness, it is one factor that can provide a reason for combining the elements in the manner claimed (KSR). Further, in the present case, the problem addressed by the up-titration of Hoch is simply the problem of first-dose effects. The fact that Olsson utilized a somewhat different solution to this problem does not render it nonobvious to combine the known solution of Hoch to first dose-effects with the known solution of Olsson to multiple sclerosis treatment.
Applicant further argues the previous Office Action mischaracterizes Hoch’s up-titration as “behind” Applicant’s up-titration, when in fact it is “ahead” (paragraph spanning the bottom of pg. 9 to the top of pg. 10 of Applicant’s Remarks). While this semantic argument is not germane to the question of obviousness, Applicant leads it to the argument that the combination of Olsson and Hoch fails to teach the method of previous claim 8 (present claim 1) because the presently claimed up-titration dosing regimen differs in some details from that of the Hoch. To that point, Applicant asserts that one of skill in the art would not have seen any defect in the up-titration of Hoch and thus would not have found it obvious to modify Hoch’s up-titration method. This argument has been fully considered, but is not found persuasive.
It is well-established that a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985) See, for example, In re Aller, 220 F.2d 454 (CCPA 1955), where a claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%. While many examples of this reasoning deal with factors like concentration and temperature, it is also applicable to a dosing regimen dealing with the analogous factors of dose amount and timing/schedule. In the present case, the claimed up-titration schedule is substantially the same as that of Hoch, differing only in modest alterations of dose amount and timing, as described in the rejection. Furthermore, there is no showing of criticality, or even outcome significance of these changes. Absent any showing of functional significance, the modest changes to the known up-titration method of Hoch are obvious variations.
Finally, Applicant argues that the showing in Olsson that ponesimod caused a slight increase in brain volume in multiple sclerosis (MS) patients would not render it obvious that ponesimod could be effective to slow MS-related brain volume loss. Tangentially related to this point, Applicant appears to have been confused by a typographical error in the Office Action, which was meant to state that “Olsson further teaches that those receiving ponesimod exhibited, on average, a 0.02%, 0.05%, and 0.23% increase in brain volume while those receiving placebo exhibited, on average a 0.26% decrease in brain volume after 24 weeks.” Applicant then asserts that “increasing brain volume is not the same as slowing a decrease in brain volume” (pg. 11, of Applicant’s Remarks, first full paragraph). The Office disagrees, and notes that Olsson shows a brain volume decrease with placebo, but a brain volume increase with ponesimod. The Office regards a reversal of brain volume loss (an increase in brain volume) to constitute a decrease in brain volume loss in the context of claim 1.
Applicant further asserts (pg. 11 of Applicant’s Remarks, second and third full paragraphs) that the results of Olsson do not support an understanding that ponesimod promotes retention/increase of brain volume. To this point, Applicant appears to argue that, in considering the data in which over 100 subjects in each group (placebo, or, 10, 20, or 40 mg ponesimod) were evaluated, one should ignore the mean outcome for those 100+ subjects and only look at a single, outlier subject in each group (either the single largest brain volume increase subject or the single largest volume decrease subject). This manner of evaluating the data appears to be mere attorney argument, that is unsupported by any rationale. Furthermore, Olsson itself disagrees with Applicant’s data analysis, and agrees with the analysis applied in the rejection, relying on the mean values (“At week 24, a small mean increase in brain volume was observed with ponesimod (0.02%, 0.05% and 0.23% in the 10, 20 and 40 mg groups, respectively) compared with a mean decrease (–0.26%) with placebo.” Olsson, pg. 1203, sentence spanning the bottom of the left paragraph to the top of the right paragraph).
For the aforementioned reasons, the rejections, as modified in view of the amendments, are maintained.
Reiterated, albeit modified, rejections:
Claim 1 recites a method of slowing brain volume loss in a patient in need thereof, comprising administering ponesimod to the patient using a regimen that is effective to slow brain volume loss relative to a patient population having substantially similar baseline disease characteristics and receiving a standard of care treatment that does not include ponesimod. Amended claim 1 further recites that the administration is performed with a specified up-titration regimen.
Olsson teaches a phase IIb study on the efficacy and safety of ponesimod for the treatment of patients with relapsing-remitting multiple sclerosis (Abstract, Objective). Olsson teaches the study include oral administration of 10 mg, 20 mg, or 40 mg of ponesimod or placebo once daily to randomized subgroups of a 464 patient group (Abstract, Methods). Olsson further teaches that those receiving ponesimod exhibited, on average, a 0.02%, 0.05%, and 0.23% increase in brain volume while those receiving placebo exhibited, on average a 0.26% decrease in brain volume after 24 weeks (Table 2, and paragraph spanning the bottom of the left column to the top of the right column of pg. 1203).
PNG
media_image1.png
44
671
media_image1.png
Greyscale
PNG
media_image2.png
48
670
media_image2.png
Greyscale
Above, Modified Table 2 of Olsson.
Olsson thus teaches a method of slowing brain volume loss in a patient in need thereof (a patient having relapsing-remitting multiple sclerosis) comprising administering to the patient ponesimod in a regimen effective to slow brain volume loss (10, 20, or 40 mg daily).
With respect to further limitation that the ponesimod is effective to slow brain loss relative to a patient population receiving standard-of-care treatment, the 20 mg dosage of Olsson is inherently a regimen that is effective to slow brain volume loss relative to a patient population having substantially similar baseline disease characteristics and receiving a standard of care treatment (teriflunomide) that does not comprise ponesimod, as demonstrated by the instant specification. Inherency is of limited applicability in obviousness rejections, but is appropriate when the inherent property is necessarily present in the cited combination, and does not require any hindsight knowledge to be implemented.
Instant Example 1 is a double-blind superiority study (drug comparison) in which patients with a confirmed multiple sclerosis diagnosis are administered daily oral ponesimod (20 mg) or teriflunomide (14 mg) for up to 108 weeks, after which various effectiveness-of-treatment observations, including change in brain volume, are made. The results in instant Example 1 demonstrate that ponesimod 20 mg reduced brain volume loss of by about 27% compared to teriflunomide 14 mg (paragraph [00126]), and the instant specification (e.g. paragraph [0033]) describes Example 1 as a demonstrated example of a ponesimod regimen that is effective to slow brain volume loss relative to a patient population having substantially similar baseline disease characteristics and receiving a standard of care treatment that does not comprise ponesimod. Other than the duration of the study, the regimen of ponesimod administration in instant Example 1 is identical that in Olson: 20 mg of oral ponesimod administered daily to patients having relapsing-remitting multiple sclerosis. Therefore, the method of Olsson, comprising 20 mg ponesimod orally administered daily to patients with relapsing-remitting multiple sclerosis involves an administration regimen that inherently has the feature recited in claim 3 (is effective to slow brain volume loss relative to a patient population having substantially similar baseline disease characteristic and receiving a standard of care treatment that does not comprise ponesimod), regardless whether this characteristic had been proven at the time of publication of Olsson. Because this property is inherently present in the method of Olsson, and therefore in the method of Olsson/Hoch, instant claim 3 is obvious over Olsson and Hoch.
Finally, Olsson does not explicitly describe an up-titration such as that of amended claim 1 (Olsson employs a different up-titration), but it would have been obvious, to employ the up-titration of claim 1, because this was well-known in the art as a useful dosing approach to slowly acclimate a patient to an S1P1 receptor agonist like ponesimod and thereby avoid side effects like heart rate diminishment. See, for example, Hoch.
Hoch teaches an up-titration for administration of ponesimod, regimen A, that mitigates cardiodynamic first-dose effects (Introduction, and Conclusions). In particular, initial administration of ponesimod was known to cause a substantial decrease in heart-rate, and the novel up-titration, upon initiation of treatment, reported by Hoch substantially diminished this effect (Results). The up-titration of Hoch is substantially identical to that of instant claim 1, being only one day shifted relative to that of claim 1, with only a minor difference of having a first day of placebo and two days instead of three days at 10 mg before reaching 20 mg at day 15. It would have been obvious to initiate the method of Olsson with an up-titration of Hoch, in order to mitigate cardiodynamic first-dose effects of ponesimod. The minimal difference between the up-titration of Hoch and that of claim 1 would have been bridged by routine experimentation, especially where, as here, there is no evidence that this minor difference yields a critical difference in outcome, or any difference in outcome for that matter.
With respect to claim 3, similar to the analysis applied to claim 1, instant Example 1 demonstrates that the 20 mg ponesimod administration of Olsson or Hoch is inherently effective to slow loss of brain volume relative to a patient population receiving 14 mg daily teriflunomide.
With respect to claims 5-6 (depending from claim 1), as noted, the patients of Olsson have relapsing-remitting multiple sclerosis. With respect to claim 7, as noted, one of the treatment groups in the study of Olsson received 20 mg oral administration of ponesimod daily.
With respect to claim 9, this element is presumably exhibited by the ponesimod treatment method of instant Example 1 (and therefore inherent to the method of Olsson), or else the instant disclosure would fail to satisfy the written description requirement for this claim. Therefore, because slowing loss of white matter or grey matter is inherent to the method of Olsson, claim 9 is obvious.
With respect to claim 14-17 (depending from claim 3), as noted with respect to claims 1 and 3, the method of Olsson inherently possesses the properties of the ponesimod treatment method disclosed in instant Example 1. With respect to claim 14, this includes the relative slowing of brain volume loss relative to teriflunomide of greater than 20%.
With respect to claim 58, as noted above with respect to claim 5, the patients of Olsson have relapsing-remitting multiple sclerosis. Furthermore, with respect to claim 59, this constitutes a relapsing-remitting disease. Claim 62 combines the elements of claims 3 and 9 and is therefore obvious for the same reasons as discussed above with respect to claims 3 and 9.
Claims 2, 12-13, 50-51, and 54 are obvious over Olsson, Hoch, and Calabresi:
Claims 2, 12-13, and 50-51 are rejected under 35 U.S.C. § 103 as being unpatentable over Olsson, in view of Hoch, and further in view of the non-patent publication, Diagnosis and Management of Multiple Sclerosis, American Family Physician, 70, pgs. 1935-1940 (2004) by Calabresi (hereinafter, “Calabresi”).
Claim 2 recites a method of slowing brain volume loss in a patient in need thereof, comprising assessing cognitive deficiencies or physical deficiencies in the patient; and administering ponesimod to the patient using a regimen that is effective to slow brain volume loss. While written as an independent claim, claim 2, in effect, recites the method of claim 1, further comprising the step of assessing cognitive deficiencies or physical deficiencies in the patient.
Olsson and Hoch are applied to claim 1, above, but does not explicitly teach assess cognitive deficiencies or physical deficiencies in the multiple sclerosis patient or a prospective multiple sclerosis patient. It would have been obvious to perform such an assessment, however, because assessing cognitive or physical deficiencies in a patient were well-known at the time as useful in diagnosing multiple sclerosis. See, for example, Calabresi.
Calabresi factors in diagnosing multiple sclerosis, including common symptoms indicative of a possible MS affliction (Abstract). Calabresi teaches that common presenting symptoms include numbness, weakness, visual impairment, loss of balance, dizziness, urinary bladder urgency, fatigue (i.e. various physical deficiencies), and depression. It would have been obvious to assess the presence of such symptoms, indicative of a possible multiple sclerosis affliction, in identifying a patient suitable for the treatment method of Olsson.
With respect to claim 12, claim 12 specifies cognitive deficiencies but does not require that such cognitive deficiencies be assessed, i.e. as a claim depending from claim 2, the method requires assessing cognitive deficiencies or physical deficiencies. As such, claim 12 is obvious for the same reasons as is claim 2, based on the assessment of physical deficiencies taught by Calabresi. With respect to claim 13, Calabresi teaches symptoms include weakness (muscle weakness) and visual impairment (deficiencies associated with vision).
With respect to claims 50-51 (depending from claim 2), as noted, the patients of Olsson have relapsing-remitting multiple sclerosis. Claim 54 combines the elements of claims 2 and 9, and is therefore obvious for the reasons applied to claims 2 and 9.
Claims 8 and 61 are obvious over Olsson, Hoch, and Pouzol:
Claims 8 and 61 are rejected under 35 U.S.C. § 103 as being unpatentable over Olsson, in view of Hoch, and further in view of the non-patent publication, Statistical Analysis Plan For Clinical Study Report AC-058B301, a clinical study report published at the Centers for Disease Control website and sponsored by Actelion Pharma., pgs. 1-183, dated June 2019 and obtained online at the url: cdn.clinicaltrials.gov/large-docs/44/NCT02425644/SAP_001.pdf (referred to hereinafter, as “Actelion”).
Claims 8 and 61, depending from claim 1 and 3 respectively, recite that the method further comprises an up-titration step upon reinitiation of treatment after a discontinuation, the additional up-titration being identical to the up-titration performed at treatment onset.
Olsson and Hoch are applied to claims 8 and 61 as to claims 1 and 3, but do not expressly disclose re-initiation after discontinuation. Performance of the same up-titration at re-initiation would have been obvious, however, because this was known in the art. See, for example, Actelion.
Actelion provides extensive detail of a clinical study comparing ponesimod to teriflunomide (pg. 1). Actelion states that the same 2-week titration is implemented on Day 1 of treatment as on re-initiation following a treatment interruption of more than 3 days (pg. 17). It thus would have been obvious to repeat the up-titration of Olsson/Hoch upon re-initiation of treatment if treatment were interrupted for more than 3 days, as taught by Actelion.
Claims 10-11 and 63-64 are obvious over Olsson, Hoch, and Pouzol:
Claims 10-11 and 63-64 are rejected under 35 U.S.C. § 103 as being unpatentable over Olsson, in view of Hoch, and further in view of the non-patent publication, Therapeutic Potential of Ponesimod Alone and in Combination with Dimethyl Fumarate in Experimental Models of Multiple Sclerosis, Innov. Clin. Neurosci., 16, pgs. 22-30 (2019) by Pouzol et al. (hereinafter, “Pouzol”).
Claim 10 recited the method of claim 1 comprising administering an additional therapeutic agent in combination with the ponesimod. Olsson and Hoch are applied to claim 10 as to claim 1, above, and is applied to claim 63 as to claim 3 above, but does not explicitly teach the administration of a second therapeutic agent in addition to ponesimod. It would have been obvious to one of ordinary skill in the art to administer a second therapeutic agent with ponesimod, however, because such combination therapy was well-known in the art to be beneficial in some instances. See, for example, Pouzol.
Pouzol teaches a study of ponesimod monotherapy and a comparison to ponesimod/dimethyl fumarate (DMF) combination therapy, to investigate possible additive or synergistic benefits of the combination (Abstract, Objective). In a rat multiple sclerosis model, ponesimod monotherapy showed significant efficacy, while DMF monotherapy showed modest efficacy in ameliorating symptoms; however the combination therapy synergistically reduced the severity and prevalence of disease, and was the only treatment to fully suppress clinical disease activity (Abstract, Results). Pouzol asserts that these results support the potential therapeutic benefits of ponesimod/DMF combination therapy, and suggest that combining ponesimod with other oral agents having different mechanisms of action from that of ponesimod may be therapeutically beneficial (Abstract, Conclusion). On the basis of these teachings of Pouzol, it would have been obvious to try administering different MS-targeted therapeutic agents in combination with ponesimod, and one would have had a reasonable expectation of success in combining DMF, in particular, with ponesimod, in the method of Olsson, thus rendering claims 10-11 and 63-64 obvious.
Claims 55-56 are obvious over Olsson, Hoch, Calabresi, and Pouzol:
Claims 55-56 are rejected under 35 U.S.C. § 103 as being unpatentable over Olsson, Hoch, Calabresi, and Pouzol.
Claims 55 and 56 combine the elements of claim 2 with the elements of claims 10 and 11, respectively. Claims 55 and 56 are therefore obvious for the reasons applied to these claims.
Double Patenting
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.
Applicant’s arguments:
In its Remarks, Applicant asserts first applies the arguments presented in the prior art rejections, specifically those related to the obviousness analysis over Hoch. Those arguments are addressed above and, for the reasons discussed above, Hoch is regarded as applicable in an obviousness-type analysis.
With respect to the ‘752 application, Applicant asserts that it is directed to methods of slowing an increase in brain ventricular volume, and states this is entirely unlike and distinct from slowing a decrease in brain volume. The Examiner disagrees, regards this as mere attorney argument, and further regards increasing brain ventricular volume to be so closely related to decreasing brain volume as to be substantially the same. See, for example, the Kalkers paper cited in the rejection.
Claims 1-17 and 49-64 are rejected for nonstatutory double patenting over the ’387 application:
Claims 1-17 and 49-64 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 12,502,379 (hereinafter, “the ’379 patent”). Although the claims at issue are not identical, they are not patentably distinct from each other because The claims of the ’379 patent n substantially overlap with the instant claims.
Claim 1 of the ’379 patent recites a method of avoiding worsening of fatigue-related symptoms in a human patient suffering from multiple sclerosis and fatigue, comprising assessing the fatigue-related symptoms of the patient; and administering ponesimod to the patient using a regimen that is effective to avoid worsening of the fatigue-related symptoms. There is plainly significant overlap between this method and the method of instant claim 1 since both claim sets recite the same exemplary method: administering about 20 mg of ponesimod to the patient once daily (claim 2 of the ’379 patent and instant claim 7). To the extent that instant claim 1 represents repurposing the method of the ’379 patent for slowing decrease in brain volume, such a repurposing is rendered obvious by the teachings of Olsson, and the up-titration of instant claim 1 is rendered obvious by the teachings of Hoch.
The method of claims 1 and 6 of the ’379 patent inherently possesses the functional limitation of the dosing regimen of instant claim 3, thus rendering instant claim 3 an obvious variant of the method claimed in the ’379 patent. The elements of claims 4-6, 9, 14-17, 57-60 and 62 are, at most, obvious variations on these methods claimed in the ’379 patent, as well.
The method of instant claim 2, and of instant claims 12-13, is an obvious variant of the method of claim 1 of the ’387 application, in view of Calabresi, as discussed above in reference to the rejection of claim 2 under 35 U.S.C. § 103; and the method of claim 1 (and claim 2) of the ’379 patent inherently possesses the functional limitation of the dosing regimen of instant claim 3, thus rendering instant claim 3. Notably, inherency is applicable in this context because the inherent functional property is necessarily present in the method of at least claim 2 of the ’379 patent.
The methods of instant claims 10-11 and 63-64 is an obvious variant of the method recited in the claims of the ’379 patent, in view of the teachings of Pouzol, as discussed above.
Claims 1-17 and 49-64 are rejected for nonstatutory double patenting over the ’836 application:
Claims 1-17 and 49-64 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 12,419,869 (hereinafter, “the ’869 patent”). Although the claims at issue are not identical, they are not patentably distinct from each other because The claims of the ’869 patent substantially overlap with the instant claims.
Claim 1 of the ’869 patent recites a method for reducing clinical management events before or during treatment of multiple sclerosis in a patient in need thereof, comprising administering ponesimod in an amount and manner that is described in a drug product label for an approved drug product. There is plainly significant overlap, if not complete identity, between this method and the method of instant claim 1 since both claim sets recite the same exemplary method: administering about 20 mg of ponesimod to the patient once daily (claim 2 of the ’869 patent and instant claim 7). To the extent that instant claim 1 represents repurposing the method of the 387 for slowing decrease in brain volume, such a repurposing is rendered obvious by the teachings of Olsson, and the up-titration of instant claim 1 is rendered obvious by the teachings of Hoch.
The elements of claims 4-6, 9, 14-17, 57-60 and 62 are, at most, obvious variations on these methods claimed in the ’869 patent, as well.
The method of instant claim 2, and of instant claims 12-13, is an obvious variant of the method of claim 1 of the ’869 patent, in view of Calabresi, as discussed above in reference to the rejection of claim 2 under 35 U.S.C. § 103; and the method of claim 1 (and claim 2) of the ’869 patent inherently possesses the functional limitation of the dosing regimen of instant claim 3, thus rendering instant claim 3. Notably, inherency is applicable in this context because the inherent functional property is necessarily present in the method of at least claim 2 of the ’869 patent.
The methods of instant claims 10-11 and 63-64 is an obvious variant of the method recited in the claims of the ’869 patent, in view of the teachings of Pouzol, as discussed above.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-17 and 49-64 are provisionally rejected for nonstatutory double patenting over the ’752 application:
Claims 1-17 and 49-64 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent Application No. 18/565,752 (hereinafter, “the ’752 application”). The corresponding U.S. Patent Application Publication No. 2024/0261268 is cited in the form 892 attached to this Office Action. Although the claims at issue are not identical, they are not patentably distinct from each other because The claims of the ’752 application substantially overlap with the instant claims.
Claim 1 of the ’752 application recites a method of slowing an increase in brain ventricular volume in a patient in need thereof, comprising administering ponesimod to the patient using a regimen that is effective to slow the increase in brain ventricular volume. This is substantially the same as the method of instant claim 1, at least because a loss in brain volume is largely the same as an increase in brain ventricular volume. See, for example, the non-patent publication, Longitudinal Brain Volume Measurement in Multiple Sclerosis Rate of Brain Atrophy Is Independent of the Disease Subtype, Arch. Neurol., 59, pgs. 1572-1576 (2002) by Kalkers et al., which teaches that MS-associated losses in brain volume are typically associated with both decreases in the parenchymal fraction and increases in the ventricular fraction (Abstract, Results). This suggests that an MS treatment regimen that lessens losses in brain volume (as in instant claim 1) would also lessen increases in ventricular volume (as in claim 1 of the ’752 application). Furthermore, both claim sets recite the same exemplary method: oral administration of 20 mg ponesimod once daily (claim 6 of the ’752 application and instant claim 7).
The method of claims 1 and 6 of the ’752 application inherently possesses the functional limitation of the dosing regimen of instant claim 3, thus rendering instant claim 3 an obvious variant of the method claimed in the ’752 application. The elements of claims 4-6, 9, 14-17, 57-60 and 62 are, at most, obvious variations on these methods claimed in the ’752 application, as well.
The method of instant claim 2, and of instant claims 12-13, is an obvious variant of the method of claim 1 of the ’752 application, in view of Calabresi, as discussed above in reference to the rejection of claim 2 under 35 U.S.C. § 103; and the method of claim 1 (and claim 6) of the ’752 application inherently possesses the functional limitation of the dosing regimen of instant claim 3, thus rendering instant claim 3. Notably, inherency is applicable in this context because the inherent functional property is necessarily present in the method of at least claim 6 of the ’752 application.
The methods of instant claims 8 and 61 is an obvious variant of the method recited in the claims of the ’752 application, in view of the teachings of Hoch, as discussed above. The methods of instant claims 10-11 and 63-64 is an obvious variant of the method recited in the claims of the ’752 application, in view of the teachings of Pouzol, as discussed above. The methods of instant claim 53 is an obvious variant of the method recited in the claims of the ’752 application, in view of the teachings of Calabresi and Hoch, as discussed above.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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 extension fee 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 ALEXANDER K SHOWALTER whose telephone number is (571)270-0610. The examiner can normally be reached M-F 9:00 am to 5:00 pm, eastern time.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey S Lundgren can be reached on (571) 272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ALEXANDER K. SHOWALTER/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
Prosecution Insights