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, 28-32, and 34 are pending. Acknowledgment is made of the amendment of claims 1, 2, and 4-15, and the addition of new claim 34, in the reply filed 08/28/2026.
Election/Restriction Requirement
Applicant elected Group I, claims 1, 2, 4-15, and 34 in the reply filed 04/13/2026.
Claims 19 and 28-32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 04/13/2026.
Withdrawn Objections/Rejections
Applicant’s amendment to the claims, filed 08/28/2026, overcomes the objection to claims 1, 2, and 4-15 for minor informalities. The objection to claims 1, 2, and 4-15 has been withdrawn.
Applicant’s amendment to the claims, filed 08/28/2026, overcomes the rejection of claims 4 and 10-15 under 35 U.S.C. 112(b) for indefiniteness. The rejection of claims 4 and 10-15 has been withdrawn.
Maintained/Modified Rejections
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, 4-15, and 34 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.
Applicant Argues:
Applicant states that to expedite prosecution, the definitions of X, X1, X2, and Z have been amended.
Examiner Responds:
Applicant's arguments have been fully considered but they are not persuasive. These amendments do not address the rejection above, specifically regarding variables R1, R2, M, c, B, Ra, m, and n. The amendments to variable X do not overcome the enablement rejection.
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, 5-7, 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.
Regarding formula (i) in claim 1, when e is 1 and n is 1, 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, claim 1 is a reach-through claim which attempts 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 2, 5-7, and 9 are rejected as being dependent upon a rejected claim and failing to give structure to the “linking group” of “X”.
Applicant Argues:
Applicant states that the claims have been amended to recite specific groups for the variable X.
Examiner Responds:
The amendment to the claims recites that “X is a linking group containing at least one member selected from…”, followed by a broad recitation of possible portions of the linker. However, the “linking group” is still indefinite, since it must only contain one of the listed members, which are also structurally undefined, and the rest of the linking group remains undefined.
New Rejections
Necessitated by Claim Amendment
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 12, 13, and 34 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 12 and 13 recite the limitation "formulas (19) to (21)". There is insufficient antecedent basis for this limitation in these claims. Formulas (19) to (21) are defined in claim 11, from which these claims do not depend.
Claim 34 recites the limitation “a pH-responsive polymer chain”. This moiety is not defined or given any structure in the claim or the specification. Therefore, the term “pH-responsive polymer chain” is rendered 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.
Claim 34 is 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.
Claim 34 states that variable X is
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, wherein “…two bonding sites of Q are each connected to a pH-responsive polymer chain”. However, claim 1, from which claim 34 depends, states that X is a trivalent group with the following connection:
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Claim 1 shows that the trivalent group is bound to a specific moiety in formula (i), and not “a pH-responsive polymer chain”, which is undefined in claim 34. Therefore, claim 34 fails to include all the limitations of the claim upon which it depends.
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.
Conclusion
Claims 1, 2, 4-15, and 34 are rejected.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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
