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 Claims
Claims 1-11 and 15-20 are pending in the instant application.
Claims 12-14 have been canceled.
Election/Restriction
This action is in response to an election from a restriction requirement filed on July 30th, 2026. There are 17 claims pending and 17 claims under consideration. This is the first action on the merits. The present invention relates to a synthetic glycerophospholipid of formula (I).
Applicant’s election with traverse of Group I, Claims 1-5, and species election of Compound Ie as recited at instant Claim 5 in the reply received September 21st, 2026 is acknowledged.
Applicant’s traversal is on the grounds that the cited compound taught by Smith et. al. (“Modular synthesis of biologically active phosphatidic acid probes using click chemistry”, Molecular BioSystems, 2009; cited in restriction requirement mailed July 30th, 2026; hereinafter referred to as Smith) does not correspond to the formula (I) of Claim 1 because Claim 1 limits R2 to mono- or polyunsaturated aliphatic chain comprising at least 14 carbon atoms.
The Examiner finds this argument persuasive. To this end, the requirement for restriction is hereby withdrawn.
Priority
Acknowledgement is made of Applicant’s claim for foreign priority based on the FR2202640 application filed in the French Republic on March 24th, 2022.
Information Disclosure Statement
The Information Disclosure Statement received September 24th, 2024 has been fully considered by the examiner, except where marked with a strikethrough.
Specification
The disclosure is objected to because of the following informalities:
Several of the structures and/or reaction schemes in the instant specification are blurred such that they are illegible. This includes all structures on Page 3-4, the reaction schemes on Pages 10-13, structure VII’ on Page 16, the reaction schemes on Pages 20-21, formula (XIV) on Page 21, the reaction scheme on Page 29, the reaction scheme on Page 34, the reaction scheme on Page 43, and the reaction scheme on Page 45 of the instant specification.
Appropriate correction is required.
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any of the errors of which Applicant may become aware of in the specification.
Drawings
Acknowledgement is made of the drawings received September 24th, 2024. These drawings are acceptable.
Claim Objections
Claims 1, 5-7, 16, 18, and 20 are objected to because of the following informalities:
Claim 1 recites “the group OR1 is chosen from…” “OR1” is shown in the structure of formula (I) with a bond drawn between O and R1. For consistency, this moiety should be referred to as “O-R1”.
Claim 5 does not end with a period. Per MPEP 608.01(m), “Each claim begins with a capital letter and ends with a period.”
Claim 6 recites “in which OR1 = OH”. In the formulae presented in the claim, “OR1” is presented with a bond drawn between “O” and “R1”. For consistency, “OR1” should be presented as “O-R1”.
Claim 7 recites “OR’1 represent a group OR1 …”. “OR’1” and “OR1” are presented in the relevant structures with a bond drawn between O and R’1 or R1. For consistency, “OR’1” and “OR1” should be presented as “O-R’1” and “O-R1”.
Claims 16, 18, and 20 recite “formula (X1V)”. For consistency with Claim 9, from which these claims depend, this should be presented as “formula (XIV)”.
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 1-4, 6-8, 15, 17, and 19 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 a glycerophospholipid of formula (I) wherein the group O-R1 is hydroxy, a choline residue, a serine residue, or an inositol monophosphate residue, R2 is a mono-, di-, or tr-unsaturated aliphatic chain comprising 14-20 carbon atoms, and R3 is a saturated aliphatic chain comprising 10-20 carbon atoms, does not reasonably provide enablement for glycerophospholipids of formula (I) in which O-R1, R2, or R3 are otherwise defined. 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 and use the invention commensurate in scope with these claims.
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (1) The breadth of the claims, (2) The nature of the invention, (3) The state of the prior art, (4) The level of one of ordinary skill, (5) The level of predictability in the art, (6) The amount of direction provided by the inventor, (7) The existence of working examples and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Nature of the invention:
The invention is drawn to a synthetic glycerophospholipid of formula (I) as recited at instant Claim 1.
Breadth of the invention:
The scope of the claimed invention is very broad, as it is drawn to any glycerophospholipid corresponding to formula (I), which is:
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This allows for myriad combination of the variables as recited at instant Claim 1. Further, the group “OR1” as recited at instant Claim 1 includes the recitation “a residue of any hydroxylated compound that is capable of forming a phosphodiester group in the sn-3 position belonging to a subclass of natural GPLs”. This is a very broad limitation that can include moieties that are presently known, but also moieties that are later discovered that are capable of forming a phosphodiester group in the sn-3 position belonging to a subclass of natural GPLs. Can Applicant “reach through” and obtain patent protection over the inclusion of chemical moieties that are either yet unknown, or those that are presently known, but later are discovered to be operable in this manner?
State of the prior art and predictability in the art:
The invention is directed toward medicine and is therefore physiological in nature. 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 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 ordinary skill in the art:
An ordinary artisan in the area of drug development would have experience in synthesizing chemical compounds for particular activities. The synthesis 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 be employed, developing a therapeutic method, as claimed, prior to synthesizing and testing compounds is generally not well-known or routine, given the complexity of certain biological systems.
The amount of direction provided and working examples:
The compound core depicted with specific substituents represents a narrow subgenus for which applicant has provided sufficient guidance to make and use; however, this disclosure is not sufficient to allow extrapolation of the limited examples to enable the scope of the compounds instantly claimed. Applicant has provided no working examples of any synthetic glycerophospholipids in which OR1, R2, and R3 were defined other than as specifically noted above.
Within the specification, “specific operative embodiments or examples of the invention must be set forth. Examples and description should be of sufficient scope as to justify the scope of the claims. Markush claims must be provided with support in the disclosure for each member of the Markush group. Where the constitution and formula of a compound is stated only as a probability or speculation, the disclosure is not sufficient to support claims identifying the compound by such composition or formula.” See MPEP 608.01(p).
MPEP § 2164.01(a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F. 2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here that Applicant is not enabled for making these compounds.
Claims 9-11, 16, 18, and 20 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 a modified glycerophospholipid corresponding to formula (XIV) as recited at Claim 9 in which O-R’1 is a residue of ethanolamine, hydroxyl, or 2-nitrobenzyl, , R2 is a mono-, di-, or tr-unsaturated aliphatic chain comprising 14-20 carbon atoms, R3 is a saturated aliphatic chain comprising 10-20 carbon atoms, R8 or R9 are a residue of 7-(prop-2-yn-1-yloxy)-2H-chromen-2-one, or R8 and R9 together form a residue of ADIBO-NBD (taught as formula XVa, for example, at Page 45 of the instant specification) or a residue of formula XVa-2 as recited at Page 50 of the instant specification does not reasonably provide enablement for modified glycerophospholipids corresponding to formula (XIV) in which OR’1, R2, R3, R8, and R9 are otherwise defined. 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 and use the invention commensurate in scope with these claims.
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (1) The breadth of the claims, (2) The nature of the invention, (3) The state of the prior art, (4) The level of one of ordinary skill, (5) The level of predictability in the art, (6) The amount of direction provided by the inventor, (7) The existence of working examples and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Nature of the invention:
The invention is drawn to a modified glycerophospholipid corresponding to formula (XIV) as recited at instant Claim 9.
Breadth of the invention:
The scope of the invention is very broad, as it is drawn to any compound of the formula:
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allowing for myriad combinations of the variables recited thereof. Further, the terms “photoactivatable group”, “fluorophoric group”, “photocrosslinkable group”, and “radiolabeling group” encompass a range of diverse chemical moieties, both presently known, and moieties that have yet to be discovered. Can Applicant simply “reach through” and obtain patent protection for residues of chemical moieties that are yet to be discovered, or those that have been discovered, but are later classified as one of the aforementioned groups?
State of the prior art and predictability in the art:
The invention is directed toward medicine and is therefore physiological in nature. 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 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 ordinary skill in the art:
An ordinary artisan in the area of drug development would have experience in synthesizing chemical compounds for particular activities. The synthesis 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 be employed, developing a therapeutic method, as claimed, prior to synthesizing and testing compounds is generally not well-known or routine, given the complexity of certain biological systems.
The amount of direction provided and working examples:
The compound core depicted with specific substituents represents a narrow subgenus for which applicant has provided sufficient guidance to make and use; however, this disclosure is not sufficient to allow extrapolation of the limited examples to enable the scope of the compounds instantly claimed. Applicant has provided no working examples of any modified glycerophospholipids in which OR’1, R2, R3, R8, and R9 were defined other than as specifically noted above.
Within the specification, “specific operative embodiments or examples of the invention must be set forth. Examples and description should be of sufficient scope as to justify the scope of the claims. Markush claims must be provided with support in the disclosure for each member of the Markush group. Where the constitution and formula of a compound is stated only as a probability or speculation, the disclosure is not sufficient to support claims identifying the compound by such composition or formula.” See MPEP 608.01(p).
MPEP § 2164.01(a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F. 2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here that Applicant is not enabled for making these compounds.
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 and 15-20 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 1 is rendered indefinite, as it is drawn to glycerophospholipids of formula (I), wherein formula (I) has a negatively charged oxygen. Many of the OR1 groups recited in the claim do not require a positively charged moiety, and therefore, the result is a group of glycerophospholipids that are not charge-balanced. Reaction conditions exemplified in the instant specification suggest the presence of a counterion, such as sodium or potassium cations. Such a counterion, however, is not recited as part of formula (I), and therefore the formula is rendered indefinite. Dependent Claims 2-4, 6-8, 15, 17, and 19 do not resolve this indefiniteness, and therefore are included in the rejection.
Claim 5 recites the limitation "wherein the glycophospholipid" in the second line of the claim. There is insufficient antecedent basis for this limitation in the claim, as Claim 1, from which Claim 5 depends, does not recite glycophospholipid.
Additionally, Claim 5 is drawn to Compounds Ia, Ib, Ic, and Id. The structures shown, however, are drawn to moieties with a negatively charged oxygen, and therefore are not charge-neutral compounds. Appropriate clarification is required.
Claim 9 is rendered indefinite, as it is drawn to modified glycerophospholipids of formula (XIV), wherein formula (XIV) has a negatively charged oxygen. Many of the OR’1 groups recited in the claim do not require a positively charged moiety, and therefore, the result is a group of glycerophospholipids that are not charge-balanced. Reaction conditions exemplified in the instant specification suggest the presence of a counterion, such as sodium or potassium cations. Such a counterion, however, is not recited as part of formula (XIV), and therefore the formula is rendered indefinite. Dependent Claims 10-11, 16, 18, and 20 do not resolve this indefiniteness, and therefore are included in the rejection.
Claims 15-20 are rendered indefinite, as they are drawn to a method of using either a glycerophospholipid of formula (I) or formula (XIV), but do not positively recite any steps thereof. Per MPEP 2173.05(q), “Attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. For example, a claim which read: "[a] process for using monoclonal antibodies of claim 4 to isolate and purify human fibroblast interferon" was held to be indefinite because it merely recites a use without any active, positive steps delimiting how this use is actually practiced. Ex parte Erlich, 3 USPQ2d 1011 (Bd. Pat. App. & Inter. 1986).”
Conclusion
Claims 1-11 and 15-20 are rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANIEL JOHN BURKETT whose telephone number is (703)756-5390. The examiner can normally be reached Monday - Friday.
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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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/D.J.B./Examiner, Art Unit 1624
/BRENDA L COLEMAN/Primary Examiner, Art Unit 1624
