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 .
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-23, and without traverse the species of: the combination comprising a PEG-lipid, cholesterol, and a phospholipid (readable on claim 14) and an ionizable fulvestrant analog (readable on claims 18 and 20) in the reply filed on 7/17/26 is acknowledged. The traversal is on the ground(s) that “claim 1 has been amended such that it now recites the entrapment of the nucleic acid molecule. Accordingly, Applicant respectfully submits that Inventions Group Ill and I are related as process of making and product made that are not patentably distinct because they both require the entrapment of a nucleic acid molecule. Rejoinder of Group I and Group Ill is respectfully requested.” This is not found persuasive because amended claim 1 filed 7/18/26 is:
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There is no language in amended claim 1 about entrapment of the nucleic acid molecule. Accordingly, Applicant’s argument is moot. The requirement is still deemed proper and is therefore made FINAL.
Claims 21 and 24-27 withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected groups and species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 7/17/26.
Claim Status
Claims 1-27 are pending.
Claims 21 and 24-27 are withdrawn.
Claims 1-20, 22 and 23 are presented for examination on the merits as they read upon the elected subject matter.
Priority
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Information Disclosure Statement
The information disclosure statements (IDSs) submitted on: 1/12/25, 1/22/25, 3/5/25 and 3/6/25; are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Rejections - 35 USC § 112
Claims 17 is 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 17 recites the broad recitation “diameter of about 1000 nm or less”, and the claim also recites “preferably 200 nm or less”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-5, 7-20, 22 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Cheng et al. (US 2022/0071916) and Sirvent et al. (ChemMedChem 2017, 12, 487 – 501).
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103, the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103.
Applicant claims:
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The claims are being examined as they read upon the elected subject matter, which is the combination comprising a PEG-lipid, cholesterol, and a phospholipid and an ionizable fulvestrant analog.
Level of Ordinary Skill in the Art
(MPEP 2141.03)
MPEP 2141.03 (I) states: “The “hypothetical ‘person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988). The level of skill is that of a medicinal/pharmaceutical drug delivery research scientist, as is the case here, then one can assume comfortably that such an educated artisan will draw conventional ideas from drug delivery technology including compositions for drug delivery as well as medicinal chemistry— without being told to do so.
In addition, the prior art itself reflects an appropriate level (MPEP 2141.03(II)).
Determination of the scope and content of the prior art
(MPEP 2141.01)
Regarding claims 1, 9-16, 20 and 22, Cheng et al. is directed to nucleic acid delivery compositions (Abstract) comprising phospholipids (Claim 83), polymer conjugated lipids (Claims 86-87), steroids (Claim 88) and RNA and DNA (Claim 90), thus teaching a co-formulation of components. Cheng et al. teach that: “Lipid nanoparticles (LNPs) are the most efficacious carrier class for in vivo nucleic acid delivery. Historically, effective LNPs are composed of 4 components: an ionizable cationic lipid, zwitterionic phospholipid, cholesterol, and lipid poly(ethylene glycol) (PEG).” [0383]. Cheng et al. teach: “LNPs were prepared by mixing 5A2-SC8 (ionizable cationic), DOPE (zwitterionic), cholesterol, DMG-PEG, and DOTAP (permanently cationic) in the ratios shown in Table 1.” [0384]. Cheng et al. teach that DMG-PEG is 1,2-Dimyristoyl-sn-glycerolmethoxy(poly((ethyleneglycol) MW 2000) (DMG-PEG2000) [0476]. Cheng et al. teach compositions with fulvestrant [0378].
Regarding claim 17, Cheng et al. teach: “the formulations all fell within a size range of about 90 nm to about 160 nm” [0386], which falls within the claimed range.
Regarding claim 20, Cheng et al. teach, for example, tamoxifen and 7 other claimed species [0378].
Regarding claims 1-4, 7, 8, 13, 18 and 19, Sirvent et al. teach a fulvestrant analogue with the structure:
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(Page 494). Compound 33 contains an amine moiety and a hydrophobic group the same as claimed. Sirvent et al. report: “analogue 33 also exhibited very potent antiproliferative activity in vitro against human MCF7 cells stimulated with 17b-estradiol,[59] with an IC50 of 7.1 nm, very similar to the IC50 of 9.2 nm for fulvestrant (Table 5)” (Page 495, left column and Table 5). The amine group would appear to naturally have an experimentally determined pKa of between 4 and 11 and since it is derived from fulvestrant, then that must also be a non-colloidal forming active substance which has been modified with an amine to form ionizable colloidal forming active substance that can make aggregates.
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02) and Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
1. The difference between the instant application and Cheng et al. is that Cheng et al. do not expressly teach adding the fulvestrant analog claimed. This deficiency in Cheng et al. is cured by the teachings of Sirvent et al.
1. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to make the nucleic acid delivery composition of Cheng et al. by adding the fulvestant analog, as suggested by Sirvent et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to do this because as noted above, Cheng et al. teach compositions with fulvestant and Sirvent et al. teach that the fulvestant analog is equally as potent. The ordinary artisan would either add the fulvestant analog to a composition with fulvestant for an additive effect or substitute fulvestant for the fulvestant analogue or combine the fulvestant analog with other claimed active agents for multi-functional action with a reasonable expectation of success. See MPEP 2144.06(I) COMBINING EQUIVALENTS KNOWN FOR THE SAME PURPOSE “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition which is to be used for the very same purpose.” In re Susi, 58 CCPA 1074, 1079--80, 440 F.2d 442,445 (1971). “Where two known alternatives are interchangeable for a desired function, an express suggestion to substitute one for the other is not needed to render a substitution obvious." In re Fout 675 F.2d 297, 301 (CCPA 1982).
2. The difference between the instant application and Cheng et al. is that Cheng et al. do not expressly teach a co-formulation free of ionizable lipid. This deficiency in Cheng et al.
2. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to make the nucleic acid delivery composition of Cheng et al. free of ionizable lipid, and produce the instant invention.
One of ordinary skill in the art would have been motivated to do this because the ordinary artisan would do so as a control formulation to ascertain the properties and characteristics provided by the presence or absence of an ionizable lipid in the co-formulation. The ordinary artisan would do so with a reasonable expectation of success.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Cheng et al. (US 2022/0071916) and Sirvent et al. (ChemMedChem 2017, 12, 487 – 501), as applied to claims 1-5, 7-20, 22 and 23 above, in view of Donders et al. (Adv. Sci. 2023, 10, 2300311: 12 pages; (May 10, 2023)) and/or Shoichet et al. (WO2020252581; of record).
Applicant claims:
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The references of Cheng et al. and Sirvent et al. are discussed in detail above.
Regarding claim 6, Donder et al. teach fulvestant analogs wherein the modification comprises addition of a piperidine, pyrrolidine or imidazole chemical group to the non-colloid forming active substance in Figure 2:
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Regarding claim 6, Shoichet et al. teach in Figure 45 an imidazole fulvestant analog:
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Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02) and Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
1. The difference between the instant application and Cheng et al. and Sirvent et al. is that Cheng et al. and Sirvent et al. do not expressly teach adding the fulvestant analog wherein the modification comprises addition of a piperidine, pyrrolidine or imidazole chemical group to the non-colloid forming active substance claimed. This deficiency in Cheng et al. and Sirvent et al. is cured by the teachings of Donders et al. and/or Shoichet et al.
1. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to make the nucleic acid delivery composition of Cheng et al. and Sirvent et al. by adding the fulvestant analog, as suggested by Donders et al. and/or Shoichet et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to do this because the fulvestant analogs are functional equivalents to the fulvestant taught by Cheng et al. and Sirvent et al. It is then obvious to employ the analogs taught by Donders et al. and/or Shoichet et al. in the nucleic acid co-formulation of Cheng et al. and Sirvent et al. with a reasonable expectation of success. “Where two known alternatives are interchangeable for a desired function, an express suggestion to substitute one for the other is not needed to render a substitution obvious." In re Fout 675 F.2d 297, 301 (CCPA 1982).
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the combined references, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERNST V ARNOLD whose telephone number is (571)272-8509. The examiner can normally be reached M-F 7-3:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian Y Kwon can be reached at 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ERNST V ARNOLD/Primary Examiner, Art Unit 1613
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