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 .
Status of the Claims
Claims 1-14 are pending.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. Instant application is a U.S. National Stage Entry of PCT/EP2022/060742, filed 04/22/2022. PCT/EP2022/060742 claims priority of foreign application EP21170274.1, filed 04/23/2021. Therefore, the effective filing date is 04/23/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/20/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Election/Restriction Requirement
Applicant's election with traverse of Group I, directed to compounds of formula (I), claims 1-11, in the reply filed on 04/03/2026 is acknowledged. Applicant further elected the species Example 6, shown below, directed to claims 1-11.
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Applicant’s elected species appears allowable. Therefore, according to MPEP 803.02: should the elected species be found allowable, the examination of the Markush-type claim will be extended. If the examination is extended and a non-elected species found not allowable, the Markush-type claim shall be rejected and claims to the nonelected invention held withdrawn from further consideration. The examination of the Markush-type claims has been extended to include the structural species shown below.
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Since a nonelected species has been found not allowable, examination has been expanded to include claims directed to both the elected and nonelected species, which are presently claims 1-11, to the extent that they are readable on the elected embodiment and the above identified nonelected species. Since the nonelected species has been found not allowable, subject matter not embraced by the elected embodiment or the above identified nonelected species is therefore withdrawn from further consideration.
Claims 12-14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 04/03/2026.
Objections – Drawings
37 C.F.R. 1.84:
(u) Numbering of views.
(1) The different views must be numbered in consecutive Arabic numerals, starting with 1, independent of the numbering of the sheets and, if possible, in the order in which they appear on the drawing sheet(s). Partial views intended to form one complete view, on one or several sheets, must be identified by the same number followed by a capital letter. View numbers must be preceded by the abbreviation "FIG." Where only a single view is used in an application to illustrate the claimed invention, it must not be numbered and the abbreviation "FIG." must not appear.
The drawings are objected to because the single view should not be numbered or labeled.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112
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.
Claims 1-9 and 11 are 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 compounds of formula (I) where R4 is H, C1-6 alkyl, C1-6 haloalkyl, C1-3 alkyl-C6-10- aryl, C1-3 alkyl-(5- to 10-membered- heteroaryl), or C1-3 alkyl-(5- to 10- membered heterocycloalkyl), wherein these substituents are optionally substituted with one or more C1-5 alkyl or halogen; and R6 is C1-3 alkyl, 5- to 10-membered heteroaryl, and 5- to 10- membered heterocycloalkyl; does not reasonably provide enablement for compounds of formula (I) or prodrugs 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 make the invention commensurate in scope with these claims.
To be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fd. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996). As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is "undue", not "experimentation".
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
1- the quantity of experimentation necessary,
2- the amount of direction or guidance provided,
3- the presence or absence of working examples,
4- the nature of the invention,
5- the state of the prior art,
6- the relative skill of those in the art,
7- the predictability of the art, and
8- the breadth of the claims
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
The nature of the invention
The nature of the invention relates to compounds of formula (I) and prodrugs thereof in claim 1. Such compounds are useful for modulating sortilin activity. This invention is also directed to compositions comprising said compounds.
Predictability of the art
The hypothetical compounds in claim 1 would be unpredictable in terms of one skilled in the art being able to synthesize every possible compound claimed in instant claim 1. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
In terms of the law, MPEP 2107.03 states “evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is a reasonable correlation between the activity in question and the asserted utility. Cross v. Iizuka, 753 F.2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F.2d 1322, 206 USPQ 885 (CCPA 1980); Nelson v. Bowler, 626 F.2d 853, 206 USPQ 881 (CCPA 1980).” If correlation is lacking, it cannot be relied upon, Ex parte Powers, 220 USPQ 924; Rey-Bellet and Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ 688. Indeed, the correlation must have been established “at the time the tests were performed”, Hoffman v. Klaus, 9 USPQ2d 1657.
Level of skill in the art
An ordinary artisan in the area of drug development would have experience in synthesizing and screening chemical compounds for particular activities, such as a medical doctor or chemist. Screening of new drug candidates, while complex, is routine in the art. The process of finding new drugs that have in vitro activity against a particular biological target, (i.e., receptor, enzyme, etc.) is well known. Additionally, while high throughput screening assays can often be employed, developing a therapeutic method, as claimed, is generally not well-known or routine, given the complexity of certain biological systems.
4. The breadth of the claims
The scope of the claims involves compounds of formula (I), shown below.
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Claim 1 is very broad in the number of variables and the options of substituents for each variable. There is an extremely large amount of hypothetical compounds included in claim 1 when considering all possible variables and prodrugs.
5. The amount of direction provided, the presence or absence of working examples, and the quantity of experimentation necessary
The specification only provides the synthesis of about 20 compounds. In all of the compounds synthesized, R4 is H, C1-5 alkyl, benzyl, CH3-(5- to 9-membered- heteroaryl), or CH3-(6- membered heterocycloalkyl), wherein these substituents are optionally substituted with one or more C1-4 alkyl or halogen; and R6 is C1-3 alkyl, 6-membered heteroaryl, and 6-membered heterocycloalkyl. However, it would be assumed that the inventors are also enabled for R4 being C6 alkyl or C1-6 haloalkyl; R6 being C2-3 alkyl; R4 being C1-3-(6- to 10- membered aryl), C1-3-(5- to 10- membered heteroaryl), or C1-3-(5- to 10- membered heterocycloalkyl); and R6 being 5- to 10-membered heteroaryl or 5- to 10-membered heterocycloalkyl, since these substituents are similar in size and reactivity.
Synthesis methods are not taught in the specification to provide for the aforementioned variables to include all of the possible substituents listed in the claims. It would be expected that the varying ring sizes (e.g., C3-20 aryl and heteroaryl groups) and heteroatoms in the rings (e.g., R4 and R6 heteroaryl or heterocycloalkyl rings) would change the reactivity of the compounds, and therefore may require alternate synthesis methods. It could also be possible that some combinations of compounds may not be able to be synthesized due to their instability (e.g., where R4 and R6 are both C20-aryl or heteroaryl groups). It would require one skilled in the art, such as a chemist, to perform thousands of reactions to determine which compounds of formula (I), and prodrugs thereof, can be prepared and would require synthesis methods other than those provided in the specification. This is undue experimentation given the limited guidance and direction provided by Applicants.
Accordingly, the instant claims do not comply with the enablement requirement of 35 U.S.C. 112(a), since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
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 1-11 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.
Regarding claim 1, the phrase "prodrug" renders the claims indefinite because the claim includes elements not actually disclosed (those encompassed by "prodrug"), thereby rendering the scope of the claims unascertainable. There are no example compounds of prodrugs provided in the specification or the claims, and the specification uses open language such as “include, but are not limited to” when listing possible changes that are needed to be made to synthesize prodrugs of the instant compounds (specification, page 15). Therefore, the term “prodrug” renders the scope of the claims indefinite, because an indefinite number of compounds are included in claim 1. This rejection would be overcome if the term “prodrug” was removed.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1 and 4-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by the compound N-[N-(3-methyl-1-oxobutyl)-L-phenylalanyl]-L-Norleucine (STN Registry, RN 119626-09-4, 17 March 1989).
The compound N-[N-(3-methyl-1-oxobutyl)-L-phenylalanyl]-L-Norleucine, shown below, reads on claims 1, 2, and 4-8, where R1, R2, and R5 are -H; R3 is -CH3, R4 is -CH3-phenyl; and R6 is -i-butyl.
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Claims 1, 4, 6-9, and 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ganellin et al. (Inhibitors of Tripeptidyl Peptidase II. 2. Generation of the First Novel Lead Inhibitor of Cholecystokinin-8-Inactivating Peptidase: A Strategy for the Design of Peptidase Inhibitors, J. Med. Chem., 2000, Vol. 43(4), pages 664-674).
Ganellin et al. teaches, on page 672, the compound N-Acetyl-L-valyl-L-norvaline in an aqueous composition. The compound, shown below, reads on instant claims 1, 4, 6-9, and 11, where R1, R2, R3, and R5 are -H; R4 is -i-propyl; and R6 is -CH3.
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Advisory Notice
Some additional prior art references reading on the instant claims, but not reading on the elected or non-elected species, that Applicant should be aware of include: EP 0315574 A2, EP 0371179 A1, EP 0578978 A1, and WO 9721663 A1, and WO 2004037159 A2.
Conclusion
Claims 1-11 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RILLA M SAMSELL whose telephone number is (703)756-5841. The examiner can normally be reached Monday-Friday, 7-3.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Murray can be reached at (571) 272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/R.M.S./Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624
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