Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
DETAILED ACTION
This action is in response to claim amendments filed 6/11/24. Claims 1-5, 7-10, 12-14, 16, and 18-24 are pending and under examination.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (p.15). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The use of the term RILUTEK®, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claim 18 is objected to because of the following informalities: abbreviations should be spelled out at their first use. Claim 18 uses the acronyms “LS” and “NPI”, which should be accompanied by their full name. Appropriate correction is required.
Claim 23 is objected to because of the following informalities: the claim recites “the treating” improves response in “a patient”. This is clearly “the patient” as it would be unreasonable to suggest that administering a drug to one patient would improve response in a different patient; however, the claim should read “the patient” to provide clear antecedent basis.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1-2, 4, 7-10, 12-14, 16, and 18-24 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.
The terms “mild-to-moderate severity”, “mild severity” and “moderate severity” are relative terms which renders the claim indefinite.
The specification uses the phrases “mild” and “moderate” throughout the specification. These terms are not provided a strict definition. Rather, the specification states that mild “may” have an MMSE (Mini-Mental State Examination) score of 20-24 (p.2), suggesting that other values or other characteristics might also define the term. The disclosure at page 20 states that mild-to-moderate is “including” an MMSE score of 14-24, again suggesting that other characteristics define this phrase or that other values might be included as well.
Example 4, however, does not use the “including” language but rather equates these states to these specific ranges of MMSE (p.37), suggesting that the MMSE is a definition of the terms.
Thus, the specification uses the same range of MMSE to exemplify these terms in some portions while using these ranges to define the terms in others. It is unclear if Applicant is explicitly defining these terms according to the MMSE score. Without definition by the MMSE, the terms are relative as, e.g., “mild” would depend on the particular score or characteristics one chooses to use in order to define that term, and different users may choose different values leading to differences in claim scope. While definition by the MMSE would render the terms definite, it is unclear that Applicant intended to do so. This is particularly true in light of, e.g., claims 3 and 5. Dependent claims must further limit a claim from which they depend. Claim 3 depends from claim 2, yet the only additional limitation is limiting “mild” to an MMSE score of 20-24, suggesting that claim 2 has a scope outside of these values though it is unclear what that scope might be. Note that the phrase “at screening” is not provided any special definition in the specification and so the broadest reasonable interpretation is that “at screening” is when the MMSE is established. The MMSE score is the result of testing, not an inherent value of the subject, and so all MMSE scores are necessarily “at screening” because the screening creates the score.
MPEP § 2173.02 (II) states that one of the purposes of examination under 35 USC § 112, second paragraph is to determine whether the claim apprises one of ordinary skill in the art of its scope and, therefore, serves the notice function required by 35 U.S.C. 112, second paragraph, by providing clear warning to others as to what constitutes infringement of the patent. See, e.g., Solomon v. Kimberly-Clark Corp., 216 F.3d 1372, 1379, 55 USPQ2d 1279, 1283 (Fed. Cir. 2000). See also In re Larsen, No. 01-1092 (Fed. Cir. May 9, 2001) (unpublished). If the language of the claim is such that a person of ordinary skill in the art could not interpret the metes and bounds of the claim so as to understand how to avoid infringement, a rejection of the claim under 35 U.S.C. 112, second paragraph, would be appropriate. See Morton Int’l, Inc. v. Cardinal Chem. Co., 5 F.3d 1464, 1470, 28 USPQ2d 1190, 1195 (Fed. Cir. 1993). In this case, it is unclear if the terms “mild” and “moderate” are defined by their MMSE scores—in which case the claims violate §112d—or if the terms “mild” and “moderate” are not defined solely by their MMSE scores—in which case the claims violate §112b.
Therefore, the claims are indefinite.
Claims 8 and 9 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.
The claims recite “about 100 to 400 mg per day” and similar language, such as administering a dosage of “about 110” or “280”. The terms such as “about 100”, “about 110”, “280” lack units to properly identify the dosage. In one interpretation, the values are meant to inherit the units of the latter “400 mg” or “350 mg”; however, this would be an assumption which does not find basis in the specification. There does not appear to be any special definition in the specification for these values nor does the specification disclose, e.g., “about 110 mg” or “280 mg”. It is equally possible that these are smaller units, such as 280µg.
Therefore, the claims are indefinite. For the purpose of examination, these values will be treated as milligrams.
Claims 18-22 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.
Claims 18-22 recites the limitation "the troriluzole treated patients". There is insufficient antecedent basis for this limitation in the claim. Claim 19 depends from claim 18, which also recites “the troriluzole”. The remaining claims all depend from claim 1, which does not recite “troriluzole treated patients”. Claim 1 recites patients treated with a riluzole prodrug of a certain formula. While the specification discloses that troriluzole is a species of this genus, there is no limitation or recitation in the claims to provide proper antecedent basis for “the troriluzole treated patients”. It is also noted that claim 1 is a method of treating “a patient” (singular); thus, there is insufficient antecedent basis for “the…patients” (plural).
Further, claim 18 refers to those administered the riluzole as “patients” but those administered a placebo as “participants”. Claims such as claim 20 refer to both groups as “participants”. It is unclear what the difference in terminology is meant to describe. The specification does not explicitly define these terms nor provide any guidance regarding the differences between a “patient” and a “participant” such that the two populations require different terms. Neither the claims nor specification define what a “participant” is participating in, and so this term is further unclear. It may be that anyone receiving a placebo for any reason is participating in receiving that placebo and so is a “participant”. The specification appears to disclose this term in the context of a clinical trial, so it may be that someone is a “participant” only if they were enrolled in NCT03605667 (p.16) or the term may include any person participating in any clinical trial.
Next, claims 18, 20, 21, and 22 provide claim limitations in the form of certain statistics that renders the claims indefinite. For example, claim 18 recites “the troriluzole treated patients (n=120)”. Setting aside that there are no troriluzole treated patients in the claim, it is unclear what limitations “n=120” is setting on the claim.
In one case, claim 18 is only infringed when a user administers the riluzole prodrug to exactly 120 patients; 119 patients and 121 patients would not infringe as that does not meet the limitation of n=120. Further, the claim is only infringed when the user administers a placebo to exactly 125 “participants” and the claim is not infringed if a different number of people are administered a placebo, including zero, i.e., omitting a placebo administration step.
In another interpretation, the claim requires at least 120 patients (119 would not infringe, but 121 patients would) for the drug and at least 125 participants for the placebo. Then, others are allowed to select a subset of, e.g., 120 patients to perform the data analysis.
Under this interpretation, there is further indefiniteness as the values obtained from such an analysis would necessarily depend on the particular subjects being selected. One of skill in the art could take 120 subjects from a cohort, perform the required analysis, and obtain the claimed results (e.g., a LS mean change from baseline of 2.3 points on the NPI score) while that same person could select a different set of 120 subjects from the same cohort and obtain results outside of those claimed (e.g., a LS mean change from baseline of 2.4 points or 2.2 points on the NPI score).
In one case, the claims are directed to these values obtained when performing the analysis across all possible combinations of subjects according to any accepted analysis method and if any combination returns the claimed results, the claim is infringed.
Alternately, the claim is only infringed when performing the specific analysis on the specific subpopulation and the claim would not be infringed if the practitioner obtained non-infringing results, irrespective of whether or not the claimed results could be obtained using a different set of subjects or a different analysis technique.
Finally, a third option for interpretation is that these claims are not setting forth an actual analysis step, but rather describing inherent results which flow from the administration step. Giving the same drug to the same subjects with the same disease will necessarily obtain the same results. Claims 18 and 20-22 may be describing those results without any analysis or subject minimum required. This is supported by the disclosure as well: the specification discloses a specific reduction to practice administering the drug and placebo to specific people. The claims are (potentially) not limited to administration to those specific, unidentified people. However, by putting these results in the claims, it is being suggested that any arbitrary 120 people who have mild-to-moderate AD who are administered this drug will result in the claimed outcome statistically. Under such an interpretation, it is unclear what the “versus” portion of the claim is meant to indicate as there would be no placebo administered and therefore no “result” inherent to the administration of the drug relevant to a placebo. It is not the case that all people with mild-to-moderate AD who go untreated (placebo) will necessarily have a LS mean change from baseline of 3.8 points on the NPI score after 48 weeks, which further confuses the scope of the claim; see for example claim 22 which establishes that if all 120 drug treated patients and all 125 placebo treated patients in claim 18 have mild AD—which is within the scope of claim 18—the change will be 2.1 and 4.2, which may or may not be within the scope of claim 18.
For the statistics reported, the claims are also unclear how the mean and the confidence interval are meant to define infringement. Claim 18 requires a LS mean change from baseline of exactly 2.3 points on the NPI score when evaluating 120 subjects vs exactly 3.8 points when evaluating 125 participants; however, the claim also sets forth a confidence interval of -4.08, 1.10, suggesting that these means fall within a range. While the person of skill in the art understands the statistical meaning behind these averages and CIs, it does not clearly and unequivocally set forth the metes and bounds of legal protection sought. The claim requires a specific mean change from baseline while simultaneously claiming that the change is within a range. It is possible that the CI is the statistical range (as understood by the skilled artisan) but is merely illustrative of a potential range of outcomes but does not contradict the strict requirement of the claim to have a baseline change of, e.g., 2.3 points. However, it may also be directly contradicting the earlier requirement of 2.3 points and instead establishing that the 95% CI variance is within the scope of the claim.
Overall, the statistics set forth in claims 18 and 20-22 are highly specific to the subjects chosen and the analysis performed. While one of skill in the art understands the values in the context of a statistical analysis, one is not fairly warned as to how these statistics are meant to define the boundaries of legal protection sought by the claims.
Finally, claims 20, 21, and 22 recite that the participants “may” have these statistical changes. Thus, it is further unclear if any of the claim text is a limitation at all. It is possible that these are just examples of potential outcomes (“may”) but are not meant to limit the claim. If this is the case, Applicant is reminded that “[d]escription of examples or preferences is properly set forth in the specification rather than the claims” (MPEP §2173.05(d)).
Therefore, claims 18-22 are indefinite.
Claim 19 is 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.
The claim recites the phrase “only”. It is unclear what meaning this term places on the scope of the claims. For example, the claim recites treating “only mild [AD] patients”. In one interpretation, this means that the patients do not have the other severity levels of AD, e.g., they do not have moderate AD. However, this is not clearly supported by the rest of the claim. Another choice is “only ApoE positive patients”; the ApoE status of a subject does not determine whether the subject has mild AD and so the term “only” might refer to the subject not having one of the other elements on the list. This would not be reasonable, however, because a subject must be either ApoE positive or ApoE negative. This is further undermined by “and any combinations thereof” as one cannot treat both “only mild AD” and “only moderate AD” because in treating the combination, one is no longer treating “only mild” or “only moderate”. It is also possible that “only” is not limited to AD but rather is a broader term indicating that the patients do not have any other potential disease, e.g., “only mild AD” means that not only do the subjects not have moderate AD, but they also have no other pathology or disease. This interpretation, however, fails to account for “only ApoE positive” or “only ApoE negative” as one cannot have “only” this one gene designation and no other genes (positive or negative).
Taken as a whole, it is entirely unclear what the scope of claim 19 is meant to be. It is unclear what is meant to be excluded by the term “only”, particularly as the element of the Markush list are unrelated (mild/moderate AD vs ApoE status) and including the “any combination thereof” which seems to contradict the “only” (see §112a rejection below).
Therefore, claim 19 is indefinite.
Claim 19 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of mild/moderate AD in the same list as ApoE +/- is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
A subject with either ApoE + or ApoE- status may still have either mild or moderate AD, while a subject with mild or moderate AD may be of either ApoE status. The two subgroups do not belong to the same art-recognized class. Mild or moderate AD refers to the severity of Alzheimer’s disease in a subject while ApoE status is a genotype. While ApoE status has been disclosed as correlated to AD, all humans have an ApoE status even if they are healthy and anyone with moderate AD did, at some point, pass through the mild AD stage. Thus, while the art recognizes some connection, they are not considered part of the same “class” as they describe two separate things (disease severity vs genotype). Further, there is no disclosure that they are functionally equivalent or have a common use. Selecting subjects by their ApoE type is not functionally equivalent to selecting a subject based on disease severity. As above, an ApoE + subject may have both mild or moderate AD, while a subject with moderate AD may be either ApoE+ or ApoE-.
These elements in the list do not describe alternative chemical compounds, so the second prong of the Markush analysis (substantial structural feature) does not apply.
Therefore, the grouping of mild/moderate AD is presented as an improper alternative to ApoE+/-, forming an improper Markush group.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claims 23 and 24 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.
Claim 23 requires the treatment to provide “an improved response in a patient”. It is unclear what the metes and bounds of “response” is for the claim. The specification uses “improved response” only twice (p.2 and 5) and both times only using the same language as in claims 23 and 24. While the species in claim 24 serve to support claim 23, these are clearly only examples of “response” (see. 2, “one or more areas including”, i.e., not limited to) and it is unclear what other responses are meant to be included in the claim scope. A “response” could include any number of possibilities: response to the drug, response to a co-administered therapy, response to any potential medical test, etc. There is insufficient guidance in the specification to fairly warn others what is included in this broad, open-ended term. This is further exacerbated in claim 24. While these “responses” serve to support the genus of “response”, several include the term itself. In determining what meets the limitations of “improved response”, one could evaluate “overall response rate” or “duration of response”. Without knowing what the response is, one could not evaluate the duration of that response. For example, in order to determine whether a subject has improved their overall response rate, one must answer the question “response to what?”. If a subject has improved response rate to one test but not another, or improves response rate in a motor skill evaluation but not a neurological evaluation, then one person could conclude the claim is infringed (a response rate was improved) while another could conclude the claim was not infringed (a response rate was not improved). It is unclear if claim 23 requires measuring and testing of any and all possible ways a patient may “respond” in order to determine if there is any improvement by any metric, or if infringement is only determined based on those responses chosen to evaluate. If one person does not evaluate a particular metric, is the claim infringed if that metric would have shown improvement had it been measured? While breadth is not the same as indefiniteness, in this case the breadth of the term coupled with the vague requirements for a “response” leads to confusion over the claim scope.
The same logic can be applied to other terms. The claim recites “delay of onset”, but does not specify “onset of what?”. The subject necessarily already has Alzheimer’s disease, so this is not onset of the disease. Thus, this may be referring to some outward symptom, physiological process, or any number of other possibilities. The phrase “quality of life” is a relative term; different patients and practitioners will evaluate this phrase based on different criteria. A medical practitioner may conclude some aspect of the quality of life of the patient has improved; if the patient disagrees, arguing that this aspect has not improved or that their overall quality of life has not improved, it would be unclear from the claim in light of the specification whether or not the claim was infringed.
Therefore, claims 23 and 24 are indefinite.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 3 and 5 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
As above, it is unclear if the terms “mild” and “moderate” are meant to be defined by the MMSE scores of 20-24 and 14-19, respectively. If this is the case, then claims 3 and 5 fail to further limit the claims because these claims simply reiterate those definitions. Further, as above, the phrase “at screening” does not offer a further limitation as it is the screening, i.e., the administration of the MMSE, which establishes the score.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 19 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for selecting patients according to the criteria set forth, does not reasonably provide enablement for “any combination thereof”. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Claim 19 requires selecting patients from elements listed in a Markush group. For example, the patients treated according to claim 18 are patients that only have mild AD or those patients that only have moderate AD. However, the claim also includes “any combination thereof”. These two are mutually exclusive and so there is no way to select patients that “only” have mild AD and also “only” have moderate AD, as having one (e.g., mild) necessarily means they do not have the other (e.g., moderate). The same is true of the binary ApoE4 positive vs negative. One cannot select patients that are both “only” ApoE4 positive as well as “only” ApoE4 negative, as being positive necessarily means the patients are not negative.
Further, a reasonable interpretation of the phrase does not include the patients having “either”, e.g., the claim cannot be interpreted to be that the patient is “either ApoE positive or ApoE negative”. This is because it would require ignoring the term “only” which is recited four times in the claim. Additionally, such an interpretation would cause the claim to violate §112(d), since this would fail to provide a further limitation. All subjects with AD are either ApoE positive or negative. Additionally, the scope of claim 1 is limited to those with mild-to-moderate AD and so the combination of “mild or moderate AD” would fail to further limit the claim.
Therefore, claim 19 is not enabled for the full scope.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-5, 7-10, 12-14, 16, and 18-24 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Coric ‘324 (WO 2020023324; IDS 6/20/24 foreign citation 1).
The applied reference has a common assignee (Biohaven therapeutics). While the document meets the criteria for §102(a)(2), it is excepted under §102(b)(2)(c) as this is evidence that the applications were commonly owned no later than the filing date of the instant application.
The applied reference has a common inventor with the instant application. The applied reference meets the criteria for §102(a)(1) as it was published on 1/30/2020, which is before the instant effective filing date of 1/18/2021. However, as this date is within 12 months, there is the potential to provide evidence to meet the exception criteria under §102(b)(1). There is no prima facie exception because there is insufficient evidence explaining the contributions of inventor Irfan Qureshi on the reference document, who is not listed as an inventor of the current application.
Applicant may rely on the exception under 35 U.S.C. 102(b)(1)(A) to overcome this rejection under 35 U.S.C. 102(a)(1) by a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application, and is therefore not prior art under 35 U.S.C. 102(a)(1). Alternatively, applicant may rely on the exception under 35 U.S.C. 102(b)(1)(B) by providing evidence of a prior public disclosure via an affidavit or declaration under 37 CFR 1.130(b).
Regarding claim 1, Coric ‘324 teaches a method of treating Alzheimer’s disease (AD) (claim 1) by administering an effective amount of a riluzole prodrug having the same formula as instant claim 1 (reference claim 2). Coric ‘324 teaches this administration is explicitly to “patients with mild to moderate Alzheimer’s disease” (see study beginning on page 17). This anticipates every limitation of claim 1.
Regarding claims 2 and 4, the teaching of “mild to moderate” allows the immediate envisaging of both “mild” and “moderate”.
Regarding claims 3 and 5, Coric ‘324 teaches “mild to moderate” is defined by MMSE scores of 14-24 (p.18) and p.26 defines these scores “at screening”. Page 19 defines these into two groups: MMSE 14-19 and MMSE 20-24. Coric ‘324 teaches that lower scores indicate more cognitive impairment (p.30), thereby teaching that the 20-24 is the “mild” group while 14-19 is the “moderate” group.
Regarding claim 7, Coric ‘324 teaches the same formula (p.4;8), referring to the prodrug as troriluzole, which is “especially preferred”, anticipating the claim.
Regarding claims 8-10 and 12-13, Coric ‘324 exemplifies “280 mg once per day” and “140 mg twice per day” (p.10 L11-12). This meets the limitations of “100[mg] to 400mg per day” (claim 8), 140[mg] (claim 9), 280[mg] (claim 9), and 280 mg once per day/140 mg twice per day (claim 10). This also meets the broader criteria of once per day (claim 12) and twice per day (claim 13).
Regarding claim 14, Coric ‘324 teaches the riluzole prodrug in a tablet (p.11 L9).
Regarding claim 16, Coric ‘324 teaches the duration of treatment is 48 weeks (line crossing p.13-14).
Regarding claims 18, 20, 21, and 22, these claims are indefinite as above. Given the extensive indefinite terms as described in detail above, there is no meaningful interpretation of the claims that can be made. The Examiner is using an interpretation that these claims are describing some result of administration rather than an active step of the method. In such a case, Coric ‘324 teaches administering the same drug to the same people for the same reason and so must achieve the same results. Applicant's attention is directed to MPEP § 2112 (II), which states, "there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003)." Furthermore, Integra Life Sciences I Ltd. v. Merck KGaA, 50 USPQ2d 1846 (DC SCalif, 1999) makes clear that a reference teaching a process may anticipate claims drawn to a method comprising the same process steps, despite the recitation of a different intended use in the preamble or the later discovery of a particular property of one of the starting materials or end products. Further, the court has noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003). See MPEP § 2111.04).
To the extent that these might be required, Coric ‘324 teaches evaluating NPI, ADAS-Cog11, and hippocampal volume (p.18) as well as mean change from baseline (p.19). As the specific outcome is a result of the subjects and the analysis, and since Coric ‘324 teaches the same subjects and same analysis, this further supports a conclusion that the instant claims are anticipated.
Regarding claim 19, Coric ‘324 teaches grouping the subjects into mild and moderate (p.19), thus teaching administration to a group that only has mild AD and another group that only has moderate AD.
Regarding claims 23-24, these claims are results of the treatment itself. Administering the same drug to the same people for the same reason will achieve the same results (see above). Further, Coric ‘324 teaches these results (reference claim 15).
Therefore, claims 1-5, 7-10, 12-14, 16, and 18-24 are anticipated.
Claim(s) 1, 2, 4, 7-10, 12, 14, 16, and 18-24 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by ClinicalTrials (herein CT667; form 892).
Note that Clinical Trials posting of NCT03605667 includes changes up to 11/14/2023, which is after the effective filing date of the instant application. The attached copy and reference document is referring to the posting on 11/5/2019, which is prior to the 1/18/2021 effective filing date.
Regarding claim 1, CT667 teaches administering BHV4157, also known as troriluzole (p.11), to treat patients with mild to moderate Alzheimer’s disease. BHV4157/troriluzole is the name of the riluzole prodrug in instant claim 7. This is every limitation of instant claim 1.
Regarding claims 2 and 4, the teaching of treatment of “mild to moderate” AD allows the artisan to immediately envisage treatment of mild AD and moderate AD.
Regarding claim 7, the claimed formula is troriluzole, which is anticipated as above.
Regarding claims 8, 9, 10, and 12, CT667 teaches administering the drug at 280 mg once per day (p.10).
Regarding claim 14, CT667 teaches administration in capsules (p.11).
Regarding claim 16, CT667 teaches administration for 48 weeks (p.10).
Regarding claims 18, 20, 21, and 22, these claims are indefinite as above. Given the extensive indefinite terms as described in detail above, there is no meaningful interpretation of the claims that can be made. The Examiner is using an interpretation that these claims are describing some result of administration rather than an active step of the method. In such a case, CT667 teaches administering the same drug to the same people for the same reason and so must achieve the same results.
Regarding claim 19, CT667 teaches excluding other diseases and disorders (p.13), anticipating the subjects having only mild or only moderate AD. Further, subjects with AD are either “only ApoE positive” or “only ApoE negative” as these are binary, mutually exclusive choices, i.e., a subject cannot be both positive and negative, nor can a subject be neither positive nor negative. As such, the individual subjects being treated must meet these criteria; see also “any combination thereof” and the §112(a) rejection above.
Regarding claims 23 and 24, CT667 teaches the therapy will be evaluated using ADAS-Cog11 and CDR-sum boxes (p.11-12). Improvement in these meets the limitations of improved response as well as an improved patient reported outcome and improved quality of life. For example, improved “everyday functioning” is a metric for an improved quality of life. Note that while CT667 does not explicitly state the treatment improves these endpoints, administering the same drug to the same population for the same reason must necessarily achieve the same outcome.
Therefore, claims 1, 2, 4, 7-10, 12, 14, 16, and 18-24 are anticipated.
Claim(s) 1-2, 4, 7-10, 12, 16, 18-24 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tirumalaraju (form 892).
Regarding claim 1, Tirumalaraju teaches a study wherein troriluzole is administered to treat mild-to-moderate Alzheimer’s disease (p.1). Tirumalaraju reports that after 26 weeks, troriluzole showed a better-than-placebo benefit when evaluating cognitive function via ADAS-cog and hippocampal volume (p2). Troriluzole is a prodrug of riluzole that meets the instant formula; troriluzole is the compound of instant claim 7. Thus, Tirumalaraju teaches administering troriluzole (a riluzole prodrug of the claimed formula) to treat a patient afflicted with mild or moderate Alzheimer’s disease in an amount that obtains an intended result (therapeutically effective amount; instant specification p.8).
Regarding claims 2 and 4, Tirumalaraju teaches treating those patients with “mild to moderate” AD. If a person of skill in the art reading a reference would “at once envisage” the claimed arrangement or combination, the species of that genus may be anticipated despite not being explicitly named (MPEP §2131.02(III)). Here, the teaching of administration to those with “mild to moderate AD” allows the skilled artisan to immediately envisage the only two members of that genus: mild AD and moderate AD. Thus, these populations are anticipated.
Regarding claim 7, the claimed compound is troriluzole as described and so is anticipated as above.
Regarding claims 8, 9, 10, and 12, Tirumalaraju teaches the study administered 280mg once per day (p.3). This meets the limitations of 100 [mg] to 400 mg per day (claim 8), 280 mg per day (claim 9), 280 mg once per day (claim 10), and once per day (claim 12).
Regarding claim 16, Tirumalaraju teaches the therapeutic efficacy was determined after 26 weeks, which meets the limitations of about 8 weeks to 48 weeks.
Regarding claims 18, 20, 21, and 22, these claims are indefinite as above. Given the extensive indefinite terms as described in detail above, there is no meaningful interpretation of the claims that can be made. The Examiner is using an interpretation that these claims are describing some result of administration rather than an active step of the method. In such a case, Tirumalaraju teaches administering the same drug to the same people for the same reason and so must achieve the same results. Tirumalaraju also teaches improvement in hippocampal volume and ADAS-Cog11 versus a placebo, further supporting the conclusion that the method of Tirumalaraju achieves these results.
Regarding claim 19, subjects with AD are either “only ApoE positive” or “only ApoE negative” as these are binary, mutually exclusive choices, i.e., a subject cannot be both positive and negative, nor can a subject be neither positive nor negative. As such, the individual subjects being treated must meet these criteria; see also “any combination thereof” and the §112(a) rejection above.
Regarding claims 23 and 24, Tirumalaraju teaches improvement as determined by ADAS-Cog11 (p.2). Improvement in this meets the limitations of improved response (the patient’s response to the ADAS-Cog11 test; patient’s response to the MRI evaluating hippocampal volume) as well as an improved patient reported outcome (patient reports an improved outcome in their ADAS-Cog11 test; improved overall response for hippocampal volume).
Therefore, claims 1-2, 4, 7-10, 12, 16, 18-24 are anticipated by Tirumalaraju.
Claim(s) 1, 2, 7, 12-14, and 18-24 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wrobel (WO2016140879; form 892).
Regarding claim 1, Wrobel teaches the compound of the same formula as instant claim 1 (reference claim 1), which is a prodrug of riluzole. Wrobel teaches riluzole as a treatment for Alzheimer’s disease, including mild cognitive impairment (MCI) due to Alzheimer’s disease (claims 11 and 15). The instant phrase “mild severity” in reference to AD is indefinite (see §112b above); as Wrobel teaches “mild cognitive impairment due to Alzheimer’s disease”, this is considered to meet the criteria of a patient afflicted with Alzheimer’s disease of “mild severity”, which is included in instant claim 1’s recitation of “mild-to-moderate severity”. Thus, Wrobel teaches every limitation of the claim.
Regarding claim 2, Wrobel teaches mild severity as above.
Regarding claim 7, the only variance in the formula of Wrobel in reference claim 1 is the R23 position. This group is limited to a few, specific moieties where the first option is “H”, arriving at the instant formula. Effectively, the reference formula is the explicit naming of 23 species. As noted in MPEP §2131.02(II), a reference anticipates a species no matter how many other species are named. Further, even arguendo if the formula is considered a genus, a genus will anticipate a species when the species can be “at once envisaged” (MPEP §2131.02(III)). Given there is only a single variance with a limited number of options, this meets the criteria of “sufficiently limited or well delineated” because one could draw the structure of each of the 23 options as it would simply be appending the structural formula in the Markush group of R23 at the position designated R23 in the formula.
Regarding claims 12 and 13, Wrobel teaches the compound may be administered once per day or multiple times per day (p.214 L6-7). Note that “multiple times per day” is a minimum of two and any additional administrations, e.g., 3 or 4, would still require the drug to be administered twice in a day.
Regarding claim 14, Wrobel teaches tablet and capsule formulations for oral administration (p.214 L27).
Regarding claims 18, 20, 21, and 22, these claims are indefinite as above. Given the extensive indefinite terms as described in detail above, there is no meaningful interpretation of the claims that can be made. The Examiner is using an interpretation that these claims are describing some result of administration rather than an active step of the method. In such a case, Wrobel teaches administering the same drug to the same people for the same reason and so must achieve the same results.
Regarding claim 19, subjects with AD are either “only ApoE positive” or “only ApoE negative” as these are binary, mutually exclusive choices, i.e., a subject cannot be both positive and negative, nor can a subject be neither positive nor negative. As such, the individual subjects being treated must meet these criteria; see also “any combination thereof” and the §112(a) rejection above.
Regarding claims 23-24, these claims are results of the treatment itself. Administering the same drug to the same people for the same reason will achieve the same results (see above).
Therefore, claims 1, 2, 7, 12-14, and 18-24 are anticipated.
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.
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.
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.
Claim(s) 13-14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tirumalaraju as applied to claims 1-2, 4, 7-10, 12, 16, 18-24 above, and further in view of Coric ‘851 (WO2019094851; IDS 6/20/24 foreign citation 2).
Tirumalaraju is discussed above and incorporated herein. As above, Tirumalaraju teaches the administering 280mg once per day (p.3), but does not teach administration twice per day and is silent regarding the delivery form, e.g., capsule or tablet.
Regarding claim 13, provided with teachings of administering riluzole prodrugs including troriluzole to treat Alzheimer’s disease, one of ordinary skill in the art would have found other known dosing regimens of riluzole prodrugs obvious. One such regimen is taking the “per day” dose and splitting it into two doses of half that amount administered twice per day. Coric ‘851 teaches administration of riluzole prodrugs for the treatment of ataxia. Coric ‘851 teaches that the preferred dose is 200 mg once per day (p.5 L10-11) but that this may also be administered as 100 mg twice per day (p.5 L12-13). Coric ‘851 also exemplifies 140 mg/day or 70 mg twice per day (p.5; p.11 L24-25). In other words, Coric ‘851 teaches that riluzole prodrugs may be administered at a certain amount once per day or that same total can be split in two for twice/day administrations.
Since Tirumalaraju teaches a therapeutic dose is 280 mg administered once per day, it would have been obvious in light of the teachings of Coric ‘851 that this could also be 140 mg twice per day. There is no evidence that splitting the dose into two administrations is particular to the treatment of ataxia and so the person of ordinary skill in the art would reasonably expect this strategy to be similarly effective in AD as ultimately the same effective amount is administered.
Regarding claim 14, Tirumalaraju teaches the administration is oral (p.3) but is silent regarding the form. Coric ‘851 teaches the same drug (riluzole prodrug; troriluzole) formulated as a capsule or tablet (p.44). Coric ‘851 notes that the “typical” route of riluzole administration is “oral, e.g., by capsule or tablet”, clearly suggesting to the ordinary artisan that either the formulation of Tirumalaraju was a capsule/tablet or suggesting that the formulation should be a capsule or tablet as these are “typical”.
Therefore, claims 1-2, 4, 7-10, 12-14, 16, 18-24 would have been obvious.
Claim(s) 3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tirumalaraju as applied to claims 1-2, 4, 7-10, 12, 16, and 18-24 above, and further in view of Ray (US 20090181008; form 892).
Regarding claim 3, Tirumalaraju is discussed above and incorporated herein. While Tirumalaraju teaches the efficacy of troriluzole in treating “mild-to-moderate” AD, Tirumalaraju is silent as to how “mild” AD is assessed.
Thus, one of ordinary skill in the art finding it obvious to treat mild AD with troriluzole would seek to determine a means for establishing a subject as having mild AD.
Ray uses the MMSE score of a patient to categorize the severity of AD, teaching the same range for mild (20-24) (table 5).
Thus, it would have been obvious at the time of filing to administer riluzole prodrugs including troriluzole to AD patients with an MMSE score of 20-24 (mild) because Tirumalaraju teaches the drug is effective in treating mild AD subgroups and Ray teaches mild AD may be identified by an MMSE score of 20-24.
Therefore, claims 1-3, 4, 7-10, 12, 16, and 18-24 would have been obvious.
Claim(s) 5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tirumalaraju as applied to claims 1-2, 4, 7-10, 12, 16, and 18-24 above, and further in view of Wischik (US20200016165; form 892).
Regarding claim 5, Tirumalaraju is discussed above and incorporated herein. While Tirumalaraju teaches the efficacy of troriluzole in treating “mild-to-moderate” AD, Tirumalaraju is silent as to how “moderate” AD is assessed.
Thus, one of ordinary skill in the art finding it obvious to treat moderate AD with troriluzole would seek to determine a means for establishing a subject as having moderate AD.
Wischik uses the MMSE score of a patient to categorize the severity of AD, teaching the same range for moderate (14-19) (paragraph 392).
Thus, it would have been obvious at the time of filing to administer riluzole prodrugs including troriluzole to AD patients with an MMSE score of 14-19 (moderate) because Tirumalaraju teaches the drug is effective in treating moderate AD subgroups and Wischik teaches moderate AD may be identified by an MMSE score of 14-19.
Therefore, claims 1-2, 4-5, 7-10, 12, 16, and 18-24 would have been obvious.
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.
Claims 1-5, 7-10, 12-14, 16, and 18-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 12161633 in view of Tirumalaraju, Wischik (US20200016165), and Ray (US 20090181008). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding claim 1, reference claim 1 claims treating Alzheimer’s disease by administering troriluzole, which is a riluzole prodrug and the same compound as in instant claim 7. The difference is that reference claim 1 is directed to the genus of “Alzheimer’s disease” while the instant claims are to “mild-to-moderate” Alzheimer’s disease.
First, those portions of the specification which provide support for the patent claims may be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the patent. In re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970). The court in Vogel recognized ‘that it is most difficult, if not meaningless, to try to say what is or is not an obvious variation of a claim,’ but that one can judge whether or not the invention claimed in an application is an obvious variation of an embodiment disclosed in the patent which provides support for the patent claim. According to the court, one must first ‘determine how much of the patent disclosure pertains to the invention claimed in the patent’ because only ‘[t]his portion of the specification supports the patent claims and may be considered.’ The court pointed out that ‘this use of the disclosure is not in contravention of the cases forbidding its use as prior art, nor is it applying the patent as a reference under 35 U.S.C. 103, since only the disclosure of the invention claimed in the patent may be examined.’’’ MPEP §804(II)(B)(1).
Thus, the portions of the specification supporting the claimed treatment of Alzheimer’s disease may be inspected. The specification discloses data in support of the enablement requirement in example 1, where mild and moderate AD is treated with troriluzole. This is sufficient to conclude that the instant claims—while more specific—are an obvious variation of the reference claims. However, in addition, Tirumalaraju teaches the efficacy of troriluzole in treating mild-to-moderate AD, further supporting the conclusion that one of ordinary skill in the art at the time of filing would have found the instant claimed method an obvious variation of the reference claims.
Regarding claims 2-3, treatment of mild AD would have been obvious as above. The teachings of Ray are above and incorporated herein, rendering obvious the treatment of mild AD with an MMSE score of 20-24.
Regarding claims 4-5, treatment of moderate AD would have been obvious as above. The teachings of Wischik are above and incorporated herein, rendering obvious the treatment of moderate AD with an MMSE score of 14-19.
Regarding claim 7, this claim is directed to the structure of troriluzole, which would have been obvious as above.
Regarding claims 8-10 and 12-13, the reference document claims the same administration regimens in claims 1, 2, 3, 5, and 6, respectively.
Regarding claim 14, these limitations are in reference claims 7 and 8.
Regarding claim 16, the reference document claims the same duration (claim 9).
Regarding claims 18-22, these claims are interpreted as results of the administration step. Since the reference claims the same drug administered in the same amounts to AD, and where treatment of specifically mild and moderate AD would have been obvious, these results must flow from reference method.
Regarding claims 23-24, these are found in reference claims 11 and 12.
Claims 1-5, 7-10, 12-14, 16, and 18-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 12201618 in view of Wischik (US20200016165), Ray (US 20090181008), and Cho (US20180356397; form 892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding claims 1, 2, and 4, reference claim 1 claims treating mild-to-moderate Alzheimer’s disease by administering troriluzole, which is a riluzole prodrug and the same compound as in instant claim 7. This anticipates instant claim 1.
Regarding claim 3, the reference claims treating mild AD (mild-to-moderate). The teachings of Ray are above and incorporated herein, rendering obvious the treatment of mild AD with an MMSE score of 20-24.
Regarding claims 5, the reference claims treating moderate AD (mild-to-moderate). The teachings of Wischik are above and incorporated herein, rendering obvious the treatment of moderate AD with an MMSE score of 14-19.
Regarding claim 7, this claim is directed to the structure of troriluzole, which is part of reference claim 1.
Regarding claims 8-10 and 12-13, the reference document claim 1 recites 280 mg once per day or 140 mg twice per day, anticipating all of claims 8-10 and 12-13.
Regarding claim 14, these limitations are in reference claim 2.
Regarding claim 16, the reference document claims administration from onset of AD to the end of the patient’s life. Cho teaches the average clinical duration of AD is 8-10 years. Administration once or twice per day for 8 years necessarily includes treatment for a duration of about 8 weeks and 48 weeks. Note that the claim language does not require administration stop after 48 weeks, only that administration includes this duration.
Regarding claims 18-22, these claims are interpreted as results of the administration step. Since the reference claims the same drug administered in the same amounts to treat mild and moderate AD, these results must flow from reference method.
Regarding claims 23-24, these are found in reference claims 4 and 5.
Claims 1-5, 7-10, 12, 14, and 18-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 12121609 in view of Tirumalaraju, Wischik (US20200016165), and Ray (US 20090181008). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding claim 1, reference claim 1 and 4 claims treating Alzheimer’s disease, including mild cognitive impairment caused by AD, by administering riluzole; mild cognitive impairment caused by AD meets the broadest reasonable interpretation of “AD of mild severity” as instantly claimed. The difference is that reference claim 1 is directed to riluzole and not riluzole prodrugs.
However, Tirumalaraju teaches the efficacy of troriluzole in treating mild-to-moderate AD. One of ordinary skill in the art would have found it obvious that a prodrug of riluzole could be predictably substituted into the method claimed by the reference document with predictable results, particularly as the art teaches the efficacy of that prodrug in treating the same disease.
Regarding claims 2-3, treatment of mild AD would have been obvious as above. The teachings of Ray are above and incorporated herein, rendering obvious the treatment of mild AD with an MMSE score of 20-24.
Regarding claims 4-5, reference claim 4 claims treatment of AD, while Tirumalaraju teaches the efficacy of troriluzole in treating mild-to-moderate AD. This would have made obvious the treatment of specifically moderate AD within the genus claimed by the reference. The teachings of Wischik are above and incorporated herein, rendering obvious the treatment of moderate AD with an MMSE score of 14-19.
Regarding claim 7, this claim is directed to the structure of troriluzole, which would have been obvious as above.
Regarding claims 8-10 and 12, Tirumalaraju teaches the study administered 280mg once per day (p.3). As such, this would have been an obvious administration schedule and meets the limitations of 100 [mg] to 400 mg per day (claim 8), 280 mg per day (claim 9), 280 mg once per day (claim 10), and once per day (claim 12).
Regarding claim 14, reference claim 9 recites a tablet formulation. One could have predictably formulated a prodrug of riluzole in the same manner.
Regarding claims 18-22, these claims are interpreted as results of the administration step. Since the above makes obvious the same drug administered in the same amounts to AD, and where treatment of specifically mild and moderate AD would have been obvious, these results must flow from reference method.
Regarding claims 23-24, these are also results which flow from the method itself.
Claims 1-5, 7-10, 12, 16, and 18-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 11052070 in view of Tirumalaraju, Wischik (US20200016165), and Ray (US 20090181008). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding claim 1, reference claims 1 and 3 claim treating Alzheimer’s disease as well as mild cognitive impairment caused by Alzheimer’s disease by administering troriluzole, which is a riluzole prodrug and the same compound as in instant claim 7. Mild cognitive impairment caused by AD meets the broadest reasonable interpretation of “AD of mild severity” as instantly claimed.
Regarding claims 2-3, treatment of mild AD would have been obvious as above. The teachings of Ray are above and incorporated herein, rendering obvious the treatment of mild AD with an MMSE score of 20-24.
Regarding claims 4-5, reference claim 3 claims treatment of AD, while Tirumalaraju teaches the efficacy of troriluzole in treating mild-to-moderate AD. This would have made obvious the treatment of specifically moderate AD within the genus claimed by the reference. The teachings of Wischik are above and incorporated herein, rendering obvious the treatment of moderate AD with an MMSE score of 14-19.
Regarding claim 7, this claim is directed to the structure of troriluzole, which would have been obvious as above.
Regarding claims 8-10 and 12, Tirumalaraju teaches the study administered 280mg once per day (p.3). As such, this would have been an obvious administration schedule and meets the limitations of 100 [mg] to 400 mg per day (claim 8), 280 mg per day (claim 9), 280 mg once per day (claim 10), and once per day (claim 12).
Regarding claim 16, Tirumalaraju teaches the same duration.
Regarding claims 18-22, these claims are interpreted as results of the administration step. Since the reference claims the same drug administered in the same amounts to AD, and where treatment of specifically mild and moderate AD would have been obvious, these results must flow from reference method.
Regarding claims 23-24, these are also results which flow from the method itself.
Claims 1-5, 7-10, 12, 16, and 18-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 10639298 in view of Tirumalaraju, Wischik (US20200016165), and Ray (US 20090181008). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The reference claims riluzole prodrugs for the treatment of AD and mild cognitive impairment caused by Alzheimer’s disease. Thus, the instant claims would have been obvious for the same reasons as articulated above with respect to US 11052070.
Claims 1-5, 7-10, 12, 16, and 18-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 11911369 in view of Tirumalaraju, Wischik (US20200016165), and Ray (US 20090181008). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding claim 1, the reference claim is directed to a prodrug of riluzole (claim 1) in tablet form (claim 3). See the decisions in Sun Pharmaceuticals v Eli Lily Fed Cir July 28, 2010; Geneva v GlaxoSmithKline 349, F.3d 1373; and Pfizer v Teva 518 F3d 1353 supporting the Office’s use of disclosed utilities of compositions when applying double patenting rejections to method claims. As the reference claims are a composition of matter, the specification may be inspected for the disclosed utilities. In the reference specification, the claimed composition is used to treat Alzheimer’s disease and MCI caused by AD at the same dosages and timing as instantly claimed. The remaining claim limitations are addressed by the cited art in the same way as above with respect to US 11052070.
Claims 1-5, 7-10, 12, 16, and 18-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of copending Application No. 19/196629 in view of Tirumalaraju, Wischik (US20200016165), and Ray (US 20090181008).
The reference claims troriluzole prodrugs (R23=H) for the treatment of AD and mild cognitive impairment caused by Alzheimer’s disease (claim 11). Thus, the instant claims would have been obvious for the same reasons as articulated above with respect to US 11052070.
This is a provisional nonstatutory double patenting rejection.
Conclusion
The art made of record and not relied upon is considered pertinent to applicant's disclosure:
US 20210290599 (form 892) would constitute anticipation of the instant claims; however, the document does not qualify as prior art. The document was published on 9/23/21, which is after the effective filing date of the instant application. While the priority date is valid under §102(a)(2), the documents are both assigned to Biohaven Therapeutics and so are excepted under §102(b)(2)(c).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ADAM M WEIDNER whose telephone number is (571)272-3045. The examiner can normally be reached M-T 9-18; W-R 9-15.
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/Adam Weidner/Primary Examiner, Art Unit 1675