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 without traverse of Group I, claims 1-49, and the species “1V270” in the reply filed on 2/17/26 is acknowledged. However, Applicant has cancelled claims 1-59 and introduced new claims 60-79. New claims 60-75 read on the elected nanoparticle composition invention.
Claims 76-79 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a method for treatment that would have been restricted if they were presented earlier, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 2/17/26.
Claims Status
Claims 1-59 are cancelled.
Claims 60-79 are pending.
Claims 76-79 are withdrawn.
Claims 60-75 are presented for examination.
Priority
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Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 12/19/23 and 2/17/26 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
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.
Claim 61 recites the limitation “the micelle”. There is insufficient antecedent basis for this limitation in the claim. Claim 60 is directed to a genus of nanoparticles and comprises an amphiphilic micelle-forming agent but is not necessarily a micelle. Dependent claim 74 confirms the Examiner’s position by introducing a variety of nanoparticle species including a micelle. Correction is required.
Claim 72 is dependent upon claim 60 and recites the limitation “the TLR7 agonist of formula (IA) is 90:10 (MBS8)”. There is insufficient antecedent basis for this limitation in the claim. Claim 60 is directed to a genus of nanoparticles of formula (I) but does not describe specifically formula (IA). The specification states: “The term "MBS8" as used herein, refers to a micelle composition of DSPE-PEG2000:1V270 in a molar ratio of 90:10.” (Page 12, lines 10-11) and does not clarify the issue. Claim 71 introduces a structure according to formula (IA). Correction is required.
Claim 72 is further 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. The term “(MBS8)” is not an ordinary term of the art and does not add to the clarity of the claim. Parenthetical expressions are not permissible which do not contribute to clearness or exactness in stating Applicant’s invention (Ex parte Cahill, 1893 C. D., 78; 63 O. G., 2125). The Examiner suggests removing the term.
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 60-75 are rejected under 35 U.S.C. 103(a) as being unpatentable over Jensen et al. (WO2015036044; of record) and Jhaveri et al. (Frontiers in Pharmacology 2014;5(&&): 26 pages; of record) and Remsberg et al. (Pharmaceutics 2013;5:81-93; of record).
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 a nanoparticle composition comprising a toll-like receptor 7 agonist and an amphiphilic micelle-forming agent.
Claim interpretation: The term “toll-like” is a term of the art and is not indefinite.
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 pharmaceutical drug delivery research scientist with knowledge of lipid-based drug delivery systems. Such an educated artisan will draw conventional ideas from lipid based drug delivery materials, manufacturing, and lipid-based compositions such as emulsions, vesicular systems and particulate systems1— 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 60-65, Jensen et al. teach specific delivery of synthetic TLR7 agonists (Page 1, lines 4-5) using lipid vehicles comprising 0.1-50% lipids (Claim 35) in the form of micelles of 1 nm to 2000 nm in size (Page 1, lines 12-15; page 5, lines 5-10; page 16, lines 4-6), which overlaps the claimed range of between 5 and 25 nm. Jensen et al. appear to teach the same compounds of Formula (I), Formula (II), Formula (III) and Formula (IV) as shown in claim 1:
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See also claims 2-25 and 40 for the variables claimed. It is the Examiner’s position that the purine group in any of the formulas is subject to tautomeric rearrangements. Jensen et al. state as much: “Also it is to be understood that the purine group in any of Formula (I), (II), (III), or (IV) is subject to tautomeric rearrangements.” (Page 8, lines 11-13).
Regarding claim 66, Jensen et al. teach that at least one of the lipids is phosphatidylethanolamine (Claim 30) such as 1,2-distearoylphosphatidylglycerol (Claim 31).
Regarding claims 67, Jensen et al. teach a lipid as 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DOPE-PEG2000) (Figure 1; Example 1), which is a phospholipid conjugated to polyethylene glycol.
Regarding claims 60 and 71, Jensen et al. teach in Figure 8:
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Regarding claim 73 and 75, Jensen et al. teach pharmaceutical compositions with at least one active ingredient (Abstract; Claims 40-45) and further comprising antigens (Claim 39), which are other active agents (Page 41, lines 18-22).
Regarding claims 74, Jensen et al. teach liposomes (Claim 38) as well as micelles, cubosomes and worm-like micelles (Page 5, lines 5-10).
Regarding claims 60, 66-69 and 72, Jhaveri et al. teach that polymeric micelles, self-assembling nano-constructs of amphiphilic copolymers with a core-shell structure have been used as versatile carriers for delivery of drugs (Abstract) where polymeric micelles are spherical, colloidal, supramolecular nanoconstructs (10–100 nm) (Page 2, left column last paragraph). Jhaveri et al. teach hydrophilic bock of PEO/PEG is the most frequently utilized by far and DSPE (Page 2, right column 2nd paragraph). Jhaveri et al. teach DSPE-PEG2000 (Table 2, Table 4).
Regarding claims 60, 66-69 and 72, Remsberg et al. teach that DSPE-PEG2000 has received regulatory approval in the US and Europe and has promising kinetic and thermodynamic stability and biocompatibility (Page 83, 4th paragraph).
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)
The difference between the instant application and Jensen et al. is that Jensen et al. do not expressly teach a nanoparticle composition comprising DSPE-PEG2000 in a molar ratio with the TLR7 agonist of from 50:50 to 99.5:0.5 or 80:20 to 95:5 or 90:10. This deficiency in Jensen et al. is cured by the teachings of Jhaveri et al. and Remsberg et al.
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to make a nanoparticle lipid vehicle to deliver the claimed TLR7 agonists with DSPE-PEG2000 in a molar ratio with the TLR7 agonist of from 50:50 to 99.5:0.5 or 80:20 to 95:5 or 90:10, as suggested by Jhaveri et al. and Remsberg et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to do this because Jensen et al. expressly teach making lipid vehicle compositions with at least one type of lipid that self-associates into an aggregate in water such as micelle and liposomes (Page 16, lines 4-6). Thus, Jensen et al. is open to those types of lipids. Furthermore, Jensen et al. teach molar ratios of lipids in liposome formulations of lipid:TLR7 agonist of, for example, 95:5 and 90:10 (Table 1 of Figure 9; see also Figure 14). Jensen et al. have embodiments and teach DOPE-PEG2000 in one embodiment (Example 1, page 42), which is a pegylated phospholipid. In looking to the art for appropriate materials to make micelles and liposomes, the artisan find that another pegylated phospholipid DSPE-PEG2000 is already approved for regulatory use by the USA and Europe and has promising kinetic and thermodynamic stability and biocompatibility as taught by Remsberg et al. Accordingly, the ordinary artisan is strongly motivated to select the functionally equivalent pegylated phospholipid DSPE-PEG2000 for those desirable properties of DSPE-PEG2000 taught by Jhaveri et al. and Remsberg et al. to make the micelle embodiment of Jensen et al. with DSPE-PEG2000 in a molar ratio with the TLR7 agonist of from 50:50 to 99.5:0.5 or 80:20 to 95:5 or 90:10 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.
Claim 66 is further rejected under 35 U.S.C. 103(a) as being unpatentable over Jensen et al. (WO2015036044) and Jhaveri et al. (Frontiers in Pharmacology 2014;5(&&): 26 pages) and Remsberg et al. (Pharmaceutics 2013;5:81-93), as applied to claims 60-75 above, in further view of Sheu et al. (US20170035701; of record) and Cabral et al. (Chemical Reviews 2018; 118:6844-6892; of record).
Applicant claims:
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The references of Jensen et al., Jhaveri et al. and Remsberg et al. are discussed in detail above and that discussion is incorporated by reference.
Further regarding claim 66, Sheu et al. teaches amphiphilic lipids such as lipid-polyethyleneglycol conjugate, phospholipid, or cholesterol or a combination thereof [0041] to make micelles that include “phospholipid, poloxamer, poloxamine, Ll21, TPGS, tween, or ethoxylated hydrogenated castor oil, pegylated phospholipid, PLGA, PLA, PGA, and a combination thereof. Preferably, the amphiphilic polymer is phospholipid, Pluronic Pl23, DSPE-PEG2000, Ll21, TPGS or PLGA or a combination thereof.” [0043]. Pluronic P123 is a poloxamer and tween is a polysorbate. See also claims 1-13.
Further regarding claim 66, Cabral et al. teach block copolymer micelles in nanomedicine applications (Title) with common hydrophilic polymers for the shell of polymeric micelles including polyethylene glycol (Table 1) as well as polymers commonly used as core-forming segments of polymeric micelles including polyamino acids and polyesters (Table 2).
Jensen et al., as combined with Jhaveri et al. and Remsberg et al., do not expressly teach all the amphiphilic micelle forming agents of claim 66. This deficiency in Jensen et al. as combined with Jhaveri et al. and Remsberg et al. is cured by the teachings of Sheu et al. and Cabral et al.
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to use any of the amphiphilic micelle forming agents of instant claim 66, as suggested by Sheu et al. and Cabral et al., to make a micelle in the delivery system of Jensen et al. as modified by Jhaveri et al. and Remsberg et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to do this because these amphiphilic materials are known for making micelles, as taught by Sheu et al. and Cabral et al., and the ordinary pharmaceutical artisan readily understands the amphiphilic nature of the claimed species in making micelles through the combined teachings of the references. The ordinary artisan would do so with a reasonable expectation of success in making micelles. Furthermore, it would appear to be simple substitution one amphiphilic species for another to serve the same purpose of making micelles. "The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results." KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 417 (2007). Moreover, “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.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 60-75 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 12318481 (of record). Although the claims at issue are not identical, they are not patentably distinct from each other because the patent is a species (micelles) of the instantly claimed genus of nanoparticles and also teaches methods of treating cancer (Claims 18, 20-22) with a toll-like receptor 7 (TLR7) agonist (Claim 19) where the composition comprises TLR7 agonists of formula (I-IV) and is a micelle with an average diameter from 5-25 nm (Claim 1) with a particular structure (Claim 14) with amphiphilic micelle-forming agents (Claims 6-13).
Accordingly, the ordinary artisan would have recognized the obvious variation of the instantly claimed subject matter over the patented subject matter.
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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/ERNST V ARNOLD/Primary Examiner, Art Unit 1613
1 See for example Figure 3 in: Shrestha et al. “Lipid-Based Drug Delivery Systems” Hindawi Publishing Corporation Journal of Pharmaceutics Volume 2014, Article ID 801820, 10 pages.
Prosecution Insights