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 .
DETAILED ACTION
This Office action is responsive to restriction requirement, filed May 20, 2026. As filed, claims 1-30, 69-75 are pending in the instant application. Claims 31-74 are cancelled.
Priority
This application filed 05/23/2023 is a National Stage entry of PCT/US2021/060642 , International Filing Date: 11/23/2021; PCT/US2021/060642 Claims Priority from Provisional Application 63117629 , filed 11/24/2020.
Information Disclosure Statement
Applicants' information disclosure statements (IDS) have been considered except where lined through. Please refer to Applicants' copy of the 1449 submitted herewith.
Election/Restrictions
Applicant's election of Group I, claims 1-7, drawn to sphingomyelin-drug conjugates comprising formula (1) as recited in the claims in the reply filed on 5/20/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
In response to a further requirement for the election of a single disclosed species, Applicants further elected, the compound:
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and indicated that claims 1-7 read on the elected species.
The elected species corresponds to the claimed formula I in which DRUG is camptothecin (CPT).
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The instantly elected species was searched and examined. It was determined that the elected species was free of the prior art. For this reason, the search and examination was expanded within the Markush-type claim and to consider additional species and subgenera within the generic formula of instantly claimed compounds until the claims were searched entirely.
Claims 8-30 and 69-75 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-7 will be examined on the merits herein.
Claim Objections
1.Claim 4 is objected to for being written in improper Markush format. See MPEP 2173.05(h). "When materials recited in a claim are so related as to constitute a proper Markush group, they may be recited in the conventional manner, or alternatively Instant claim should be amended as following: DELETE” or combination thereof”.
2. Claim 6 is objected for reciting improper Markush language: the recitation in claim 6 “selected from” should be changed to “selected from the group consisting of”.
3. Claim 7 is objected for reciting improper Markush language: the recitation in claim “is” should be changed to “is selected from the group consisting of”.
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 1-6 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Examination of Patent Applications Under the 35 U.S.C. 112 ¶1 "Written Description" Requirement, Rev. 1, 2008; at http://www.uspto.gov/web/menu/written.pdf.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail such that the Artisan can reasonably conclude that the inventor(s) had possession of the claimed invention. Such possession may be demonstrated by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and/or formulae that fully set forth the claimed invention. Possession may be shown by an actual reduction to practice, showing that the invention was “ready for patenting”, or by describing distinguishing identifying characteristics sufficient to show that Applicant was in possession of the claimed invention (January 5, 2001 Fed. Reg., Vol. 66, No. 4, pp. 1099-11).
In Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc) (“Ariad”), the Federal Circuit stated that “the hallmark of written description is disclosure.” A specification adequately describes an invention when it “reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date.” Id. at 1351. “A ‘mere wish or plan’ for obtaining the claimed invention is not adequate written description.” Centocor Ortho Biotech, Inc. v. Abbott Labs, 636 F.3d 1341, 1348 (Fed. Cir. 2011).
A written description of an invention involving a chemical genus, like a description of a chemical species, “requires a precise definition, such as by structure, formula, [or] chemical name,” of the claimed subject matter sufficient to distinguish it from other materials. Regents of the Univ. of Cal. v. Eli Lilly & Co., 199 F.3d 1559, 1568 (Fed. Cir. 1997) (“Eli Lilly”). The Federal Circuit commented on Eli Lilly in Ariad:
Nature and scope of the instant claims in view of the specification:
Instant claims are drawn to sphingomyelin-drug conjugate comprising Formula (I) in which L is a linker moiety; and
Drug is an anti-cancer drug.
Claims 1 and 2 recite the limitations “linker” and “drug” for the claimed sphingomyelin-drug conjugate, without providing a chemical structure for the linker or drug, or the chemical connectivity. Applicant has not described the claimed genus of sphingomyelin-drug conjugate “comprising” Formula (I) in which L is a linker moiety and Drug is an anti-cancer drug in a manner that would indicate they were in possession of the full scope of this genus, or even to describe what this genus is comprised of.
Regarding the requirement for adequate written description of chemical entities, Applicant's attention is directed to the MPEP §2163.
In the instant case, the claimed "linker" the instant specification states on [0121] the linker moiety is of formulae I-1 to I-26, while the terminology “anti-cancer drug” is described at [0124] linting know compounds.
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However, the sphingomyelin-drug conjugate comprising Formula (I) in which L is a linker moiety and Drug is an anti-cancer drug - as claimed is not described adequately enough to allow one skilled in the art to ascertain that Applicant is in possession of the entire scope of that genus. Applicants have not described this genus in a manner that would allow one skilled in the art to immediately envisage the conjugated compounds contemplated for use. As such, the claims lack adequate written description for the claimed "linker", “anti-cancer drug”.
By contrast, the nature and scope of the invention described in the Specification includes the sphingomyelin-drug conjugates 1-54 as illustrated in the preparative examples on pages 84-170, which specific linker appending the drug moiety.
The specification does not show any other examples of compounds of formula I as claimed wherein variable L and Drug are as defined. The only sphingomyelin-drug compounds of instant specification are conjugates 1- 54 as shown in the examples.
The extent and content of the prior art: Applicant has provided several references in the IDS which discuss cancer immunotherapy. For example, Teitelbaum et al Immunochemistry, 1973, 735, teaches conjugates of two synthetic analogues of sphingomyelin: dihydrosphingosinephosphorylcholine (SPC) and
ceramidephosphorylethanolamine (CPE) which were bound covalently to either synthetic polypeptide or a protein.
The predictability of the aspect at issue: The instant claims are drawn to the sphingomyelin-drug conjugate comprising Formula (I). Chemistry is generally considered to be unpredictable and/or have unpredictable factors. See, e.g.,In re Carleton, 599 F.2d 1021, 202 USPQ 165, 170 (CCPA 1979) ("Although there is a vast amount of knowledge about general relationships in the chemical arts, chemistry is still largely empirical, and there is often great difficulty in predicting precisely how a given compound will behave.”).
The pharmaceutical art, that is the use of a chemical compound to affect a desired physiological activity, is generally considered to be unpredictable and/or have unpredictable factors. See, e.g., In re Fisher, 427 F.2d 833, 839 (CCPA 1970) (“In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved (emphasis added.”).
Based on the general knowledge in the art, as well as art that is particular to sphingomyelin-drug conjugates, anti-cancer drug, the claimed invention is of an unpredictable nature.
Conclusion Instant claims do not comply with the written description requirement because the disclosure does not provide a representative number of species falling within the scope of the genus sphingomyelin-drug conjugate compounds of formula 1. The specification is limited to preparation of specific sphingomyelin-drug conjugate compounds.
As pointed out above, the nature of the claimed invention is unpredictable and is not a mature art. Further, the Federal Circuit stated that the lack of any disclosure of examples may be considered when determining whether the claimed invention is adequately described. Boston Scientific Corp. v. Johnson & Johnson, --- F.3d --- (Fed. Cir. 2011). Applicant has not provided a representative number of species to suggest that Applicant was in possession of a sphingomyelin-drug conjugate compounds of formula 1 rather, Applicant has provided evidence for the preparation of the sphingomyelin-drug conjugates as provided in the examples.
As stated in MPEP 2163 II: If the application as filed does not disclose the complete structure or method of the claimed invention as a whole, determine whether the specification discloses other relevant identifying characteristics sufficient to describe the claimed invention in such full, clear, concise, and exact terms that a skilled artisan would recognize applicant was in possession of the claimed invention. The instant specification is devoid of a description for the sphingomyelin-drug conjugates comprising formula I in which L is any linker and Drug is any anti-cancer drug - in a manner that would indicate they were in possession of the full scope of this genus.
Thus, Applicants have failed to demonstrate possession of the claimed sphingomyelin-drug conjugate bearing any linker and any cancer drug.
Therefore, the breadth of the claims as reading on compounds of formula I as claimed in view of the level of knowledge or skill in the art at the time of the invention, and the limited information provided in the specification, an Artisan of skill would not recognize from the disclosure that Applicant was in possession of the sphingomyelin-drug conjugates, before the effective filing date of the claimed invention. Thus it is concluded that the written description requirement is not satisfied.
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 1-7 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.
1.Instant claims 1 and 2 recite the sphingomyelin-drug conjugate comprising Formula (I), in which variable L is a linker moiety, Drug is an anti-cancer drug.
However, the chemical formulae for said linker and drug groups are not provided in the claims, and it is not clear the site of the chemical connectivity relative to the linker group and the anti-cancer drugs to the sphingosine backbone, rendering said claim and its dependents indefinite. For example, for the conjugate 36- SM-Ester-Protoporphyrin IX, obtained by condensation of sphingomyelin via hydroxyl group
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with carboxylic group of Protoporphyrin IX of chemical structure:
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as shown on [0251] which results in ester group formation - is not clear what is the linker required by claimed formula I would be.
2.Claim 4 lists anti-cancer drugs and acronyms and recites “and combinations thereof”, rendering said claim indefinite, because it is no clear how the drugs can be chemically combined and what is the chemical connectivity of the resulting conjugate.
3. Claim 7 recites: “(1; Sphingomyelin (SM)-Ester-CPT)”, “(2; SM-Glycine-CPT)”, etc. rendering said claim ambiguous because is unclear if the limitations in the parenthesis are part of said claim.
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) 1-3 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by WO 9941266, August 19, 1999 by Liotta (hereinafter “the ‘266 publication”; cited in the PTO-892 attached herewith).
The ‘266 publication teaches on page 129 Fig 7 the compound 16a, shown below as displayed in the Registry data base , which anticipates the limitations of claimed Formula (I) in which n is 12 and claimed Formula (III), L is a linker moiety and Drug is an anti-cancer drug ( instant claims 1, 2) in which the anti-cancer drug is hydrophilic or hydrophobic (instant claim 3).
CN 3,5-Dioxa-8-aza-4-phosphatetracosan-1-aminium,
7-[(1R,2E)-1-(benzoyloxy)-2-hexadecenyl]-4-methoxy-N,N,N-trimethyl-9-oxo-,
(7S)-, salt with 4-methylbenzenesulfonic acid (1:1), 4-oxide (9CI) (CA
INDEX NAME)
CM 1
CRN 263558-22-1
CMF C47 H86 N2 O7 P
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Note: the chemical formula for linker and drug groups are not provided in the claims.
Therefore, the prior art teaches the limitation of instant claims.
Conclusion
Claims 1-7 are rejected. Claims 8-30 and 69-75 are withdrawn from further consideration.
Telephone Inquiry
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANA MURESAN whose telephone number is (571)-270-7587. The examiner can normally be reached on Monday through Friday, 8:30 am to 5:30 pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Scarlett Goon can be reached at 571-270-5241. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ANA Z MURESAN/Primary Examiner, Art Unit 1692
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