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, 2, 4-15, 19, and 28-32 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/JP2022/026863, filed 07/06/2022. PCT/JP2022/026863 claims priority of foreign application JP2021-113189, field 07/07/2021. Therefore, the effective filing date is 07/07/2021.
Information Disclosure Statement
The information disclosure statement filed 03/20/2024 fails to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because reference Doc. Nos. AO, AP, AQ, AR, AS, AU, and AV have no corresponding direct English translations provided. It has been placed in the application file, but the information referred to in these references only has not been considered as to the merits. Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a).
Election/Restriction Requirement
Applicant’s election without traverse of Group I, directed to pH-responsive lipid compounds, claims 1, 2, and 4-15, in the reply filed on 04/13/2026 is acknowledged. Applicant further elected the species compound 44, shown below, which reads on instant claims 1, 2, and 5-8. The elected species appears allowable. Therefore, examination has been expanded to include the entire scope of Group I. Claims 1, 2, and 4-15 are currently under examination.
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Claims 19 and 28-32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention or species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 04/13/2026.
Claim Objections
Claims 1, 2, and 4-15 are objected to because of the following informalities:
In claims 1 and 2, the phrase “…represented by a structure represented by…” should be changed to “…represented by…”, to remove repetition.
Claim 1 reads “…represented by>N-CH2-CH2- …” and should read “…represented by -N-CH2-CH2- …”.
In claims 1, 2, and 4, the ellipses should be removed from the formula labels.
In claims 4-15, the phrase “…in the aforementioned formula (i),…” should be removed for brevity. These claims are all dependent upon claim 1, which contains formula (i). Therefore, it is understood that the variables in the dependent claims are referring to formula (i).
Appropriate correction is required.
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, 2, and 4-15 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 R1 and R2 are independently C8-24 alkyl or acyl groups; M is C3 alkyl; c is 0; B is H; Ra is H or C(O)CH3; m is 5 to 40; n is 1; and X is
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or
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, does not reasonably provide enablement for all compounds of formula (i). 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) in claim 1. Such compounds are useful as pH-responsive lipids. This invention is also directed to compositions comprising said compounds.
Predictability of the art
The compounds synthesized in the instant specification appear novel. However, 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 indefinite amount of hypothetical compounds included in claim 1.
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 10 compounds that read on formula (i). In all of the compounds synthesized, where R1 and R2 are independently C17-18 alkyl or acyl groups; M is C3 alkyl; c is 0; B is H; Ra is H or C(O)CH3; m is 20 to 31; and n is 1. However, it would be assumed that the inventors are also enabled for R1 and R2 being independently C8-24 alkyl or acyl groups and for m being 5 to 40 since these substituents are similar in size and reactivity. Only four different X groups are included in synthesized compounds in the specification. However, variations of these four X groups with different numbers of repeating groups and alkyl chain sizes would not be expected to require alternate synthesis methods.
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 indefinite number of undefined structures included in the definition of X would change the reactivity of the compounds, and therefore would 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. It would require one skilled in the art, such as a chemist, to perform thousands of reactions to determine which compounds of formula (i) can be prepared and would likely 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, 2, and 4-15 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.
Claims 1, 2, and 4-15 recite a pH-responsive lipid “derivative” of formula (i). The term “derivative” renders the claims indefinite because it unclear whether the claims are referring a compound having formula (i), or rather a derivative of formula (i). This rejection would be overcome if the term “derivative” was changed to “compound”.
Regarding claims 1 and 2, the phrase "linking group" in the definition of “X” renders the claims indefinite because the claims include elements not actually disclosed (those encompassed by "linking group"), thereby rendering the scope of the claims unascertainable. The “linking group” is defined in the claim by how a bond is formed, and not by the structure of the linking group. Additionally, claims 1 and 2 reach-through claims which attempt to obtain protection for subject matter that is prophetic and/or has yet to be invented (“linking groups”). The metes and bounds of the “linking groups” are not defined by the claim, the specification does not provide an adequate standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the invention. Therefore, there are an indefinite number of “linking groups” falling under this definition.
Claims 5-15 are rejected as being dependent upon a rejected claim and failing to give structure to the “linking group” of “X”.
Claims 10-15 recite the limitation "the aforementioned formula (2)" when defining variable “X” and additionally and contain definitions for X1 and X2. There is insufficient antecedent basis for these limitations in the claim. Formula (2) and X1 and X2 are defined in claim 4, from which these claims are not dependent upon.
Conclusion
Claims 1, 2, and 4-15 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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/R.M.S./Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624
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