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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 7/1/26 has been entered.
Claim Status
Claims 6, 7, 12-14, 19, 20, 22-24, 27-29, 31 and 33-36 are cancelled.
Claims 1-5, 8-11, 15-18, 21, 25, 26, 30 and 32 are pending.
Claims 3, 17, 18, 21, 25, 26, 30 and 32 are withdrawn.
Claims 1, 2, 4, 5, 8-11, 15 and 16 are under examination as they read upon the elected subject matter.
Withdrawn rejections
Applicant's amendments and arguments filed 7/1/26 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Any rejection and/or objection not specifically addressed below is herein withdrawn.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
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, 2, 4, 5, 7-11, 15 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Liang et al. (WO2016000032) and Sharei et al. (US20180245089( and Herbert et al. (Nat Commun. 2021 Apr 13;12(1):13 pages) and Patil et al. (The AAPS Journal 2004; 6 (4) Article 29; 10 pages) and Ewert et al. (Top Curr Chem. 2010 ; 296: 191–226) and Zhang et al. (CN109503411; English translation provided by the Examiner) and Yang et al. (Molecular Therapy: Nucleic Acids Vol. 19 March 2020; pages 1357-1367).
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), 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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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 biomedical research scientist, as is the case here, then one can assume comfortably that such an educated artisan will draw conventional ideas from the interdisciplinary fields of nanomedicine, biomaterials, and biomedical engineering synthesize and engineer new metal-organic frameworks (MOF) with specific properties to improve intracellular active agent delivery efficiency and biocompatibility and to develop MOF-based delivery systems for therapeutic, clinical and research applications use 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, 2 and 8-11, Liang et al. claim a MOF that encapsulates an oligonucleotide biomolecule (Claims 13-14), thus making it a stabilized molecular delivery composition, and report images of ZIF-8 encapsulating oligonucleotide (Page 6, lines 4-9; Figure 4; page 29, line 24; page 31, lines 7 and 16; Page 36, Examples 3 and 11). Liang et al. teach that the expression “nucleic acid”, which includes oligonucleotides, also includes modified forms (Page 29, lines 32-33). Liang et al. teach that the expression “nucleic acid” includes non-naturally occurring modified forms (Page 29, lines 32-33). Liang et al. also teach ZIF-10 and ZIF-90 (Page 10, lines 23-25). Since Liang et al. teach the same MOF as claimed, then it will also implicitly impart improved stability over 4 weeks as compared to a comparative composition comprising the lipid-nucleic acid molecule complex without the MOF shell. “Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).” Similarly, regarding claims 8-10, these functional properties are implicit in the ZIF-8 encapsulating the oligonucleotide of Liang et al. The same MOF will confer the same stability compared to compositions without the MOF. In fact, Liang et al. state that the encapsulated biomolecule is shielded within the framework (Page 23, lines 21-24), thereby naturally stabilizing/protecting the biomolecule. The Examiner's finding is based on the principle that products of identical chemical compositions cannot have mutually exclusive properties. This is a well settled principle in patent law. See In re Papesch, 315 F.2d 381,391 (CCPA 1963) ("From the standpoint of patent law, a compound and all of its properties are inseparable; they are one and the same thing."). Where patentability rests upon a property of the claimed material not disclosed within the art, the USPTO has no reasonable method of determining whether there is, in fact, a patentable difference between the prior art materials and the claimed material. In re Best, 562 F.2d 1252, 1255 (CCPA 1977). Therefore, where the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the USPTO can require an applicant to prove that the prior art products do not necessarily possess the characteristics of his claimed product. Id. Especially when Liang et al. state: “the encapsulating framework advantageously provides a protective support for the bio-molecules. The protective capability of the framework is believed to derive from charge-based interactions between the framework and the guest bio-molecule, resulting in significant enhancement of the bio-molecule stability.” (Page 4, lines 4-7).
Regarding claim 15, Liang et al. teach that MOFs can be amorphous (aMOF) (Page 4, lines 9-10; page 8, lines 16-17; page 10, line 29 through page 11, line 7), thus making an amorphous composite with the oligonucleotide biomolecule.
Regarding claim 16, Liang et al. teach dried samples (Page 35, line 8) as well as forming the MOF precipitate in DI water and combining the MOF precipitate in ethanol (Examples 3 and 11), where water and ethanol are reasonably interpreted as being excipients.
Regarding claims 1 and 7-10, Herbert et al. “demonstrate that metastable lipid, protein-detergent, and protein-lipid supramolecular complexes can be successfully generated and immobilized within zeolitic-imidazole framework (ZIF) to enhance their stability against chemical and physical stressors. Upon immobilization in ZIF bio-composites, blank liposomes, and model transmembrane metal transporters in detergent micelles or embedded in proteoliposomes resist elevated temperatures, exposure to chemical denaturants, aging, and mechanical stresses.” (Abstract; see also Figures 1-2). Herbert et al. teach: “this composition was selected because it provides the best stabilization for our selected transmembrane proteins, the anionic nature of the formulated lipids is useful in promoting ZIF nucleation and growth” (Page 2, right column Results and discussion liposome stabilization). Hebert et al. report that: “When the lipids were doped with 1,2-dioleoyl-3-trimethylammonium propane (DOTAP), a cationic lipid, we observed less or even no Zn2+ interaction with the liposome (Supplementary Fig. 7C, D). Cationic surface charge has been shown to reduce the encapsulation yield or even prevent crystal growth, although there are strategies to overcome this” (Page 4, left column Mechanism of ZIF growth).
Regarding claims 1, 4 and 5, Sharei et al. teach lipid-nucleic acid complexes (Claims 22 and 31; [0009]) for delivery to a cell (Claims 1-3) where “the lipid-nucleic acid complex comprises a cationic lipid and optionally a neutral helper lipid. In some embodiments, the cationic lipid can include, without limitation, N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA), [1,2-bis( oleoyloxy)-3-(trimethylammonio )propane] (DOTAP), 3 ~[N-(N', N'-dimethylaminoethane )-carbamoyl]cholesterol (DC-Chol), dioctadecylamidoglycylspermine (DOGS), and 2,3-dioleyloxy-N-[2(sperminecarboxamido)ethyl]-N,Ndimethyl-1-propanaminium trifluoroacetate (DOSPA). In some embodiments, the neutral helper lipid can include, without limitation, dioleoylphosphatidylethanolamine (DOPE) and dioleoylphosphatidylcholine (DOPC).” [0069] The addition of a “helper lipid” reads on a mixture of lipids. The “nucleic acid” can be an oligomers [0029], which reads on oligonucleotides.
Regarding claim 1, Patil et al. teach anionic liposomal delivery systems for DNA transfection that are similar in transfection efficiency of cationic liposomes (lipofectamine) (Title; Abstract). Patil et al. teach: “cationic lipoplexes are successful in transfection because of the formation of the HII c (hexagonal) phase instead of the Lα (lamellar) phase due to the overall molecular inverted-cone shape of the lipid and the small, less-hydrated DOPE head group in the lipoplexes”; and: “during anionic lipoplex formation, addition of Ca2+ not only stimulates binding of DNA to the liposome (S.D.P., D.G.R., D.J.B., unpublished data, 2004), but also has been shown to promote and stabilize the formation of the HII phase, which, as in the case of cationic liposomes, is hypothesized to facilitate cellular uptake.” (Page 9, left column).
Regarding claims 1, 4 and 5, Ewert et al. teach cationic lipid-nucleic acid complexes with hexagonal phase (Page 2, Structures of CL-DNA Complexes) and teach zwitterionic neutral lipids DOPE and cationic lipids DOTAP (Figure 2). Figure 1 shows the self-assembled structures where the hexagonal phases B and C do not appear to have cationic surface charge (Figure 1):
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Regarding claim 1, Yang et al. teach optimization of oligonucleotides where the influence of the ratio of the lipid to oligonucleotide N:P ratio was investigated (Page 1359, right column last paragraph; Page 1360, Figure 2). Yang et al. teach varying the N:P ratio from 2.5 to 20 (Page 1360, left column first paragraph).
Regarding claim 1, Zhang et al. teach cationic lipid-RNA drug delivery systems with safe and high transfection efficiency (Abstract) with oligonucleotides, siRNA, microRNA or mRNA (claim 9) where the nitrogen to phosphorus ratios are from 1:1 to 10:1 or more narrowly of 3:1 to 7:1 (Claims 11-12).
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 Liang et al. is that Liang et al. do not expressly teach a lipid-nucleic acid (oligonucleotide) molecule complexed in the MOF where in the lipid nucleic acid complex comprises at least one charged lipid wherein the charged lipid is an ionizable lipid or a cationic lipid such as a mixture of lipids that are cationic and optionally comprising DOSPA and DOPE with the resulting improved stability functional characteristics wherein the lipid-nucleic acid molecule complex has a N:P ratio between about 4 and about 10. This deficiency in Liang et al. is cured by the teachings of Sharei et al., Herbert et al., Patil et al., Ewert et al., Zhang et al., and Yang et al.
1. It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to employ a lipid-nucleic acid (oligonucleotide) where in the lipid nucleic acid complex comprises at least one charged lipid wherein the charged lipid is an ionizable lipid or a cationic lipid such as a mixture of lipids including cationic lipids such as DOSPA and DOPE in the MOF of Liang et al. and achieve the claimed functional stability limitations wherein the lipid-nucleic acid molecule complex has a N:P ratio between about 4 and about 10, as suggested by Sharei et al., Herbert et al., Patil et al., Ewert et al., Zhang et al., and Yang et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to do this because for the following sound articulated reasoning with rational underpinning based upon the evidence. As noted above, Liang et al. teach and suggest using modified forms of nucleic acids, which includes modified forms of oligonucleotides. Sharei et al. teach and suggest a lipid-nucleic acid complex, which can be used to increase efficiency of delivering the nucleic acid into the cell [0069]. It is then obvious to employ the lipid-nucleic acid complex of Sharei et al., with the combination of ionizable lipids suggested by Patil et al. and/or cationic lipids suggested by Sharei et al. and Ewert et al. in the MOF-nucleic acid (oligonucleotide) system of Liang et al. with a reasonable expectation of success because the ordinary artisan understands that a hexagonal phase can form, as suggested by Patil et al. and Ewert et al., where there is no charge repulsion on the surface of the complex that would hinder or prevent formation of the MOF structure. The ordinary artisan is taught to optimize the N:P ratio to between about 4 and about 10 as suggested by Zhang et al. and Yang et al. The ordinary artisan would do so to ensure efficient delivery of the oligonucleotides with a reasonable expectation of success. Furthermore, there is an expectation of enhanced stability as taught by Herbert et al. especially when anionic lipids are employed. Additionally, from the teachings of Herbert et al. there is still an expectation of success using cationic lipids but just not as good as with anionic lipids. However, Herbert et al. suggests that there are ways to overcome that issue. Thus, there is a reasonable expectation of success in employing cationic lipids with the nucleic acid complex. Consequently, such claimed functional stability properties are implicit in the MOF system of Liang et al. as asserted above.
Claim 11 is further rejected under 35 U.S.C. 103(a) as being unpatentable over Liang et al. (WO2016000032) and Sharei et al. (US20180245089) and Herbert et al. (Nat Commun. 2021 Apr 13;12(1):13 pages) and Patil et al. (The AAPS Journal 2004; 6 (4) Article 29; 10 pages) and Ewert et al. (Top Curr Chem. 2010 ; 296: 191–226) and Zhang et al. (CN109503411) and Yang et al. (Molecular Therapy: Nucleic Acids Vol. 19 March 2020; pages 1357-1367), as applied to claims 1, 2, 4, 5, 8-11, 15 and 16 above, in further view of Gao et al. (Chem 2019;5:1597-1608).
Applicant claims:
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The references of Liang et al., Sharei et al., Herbert et al., Patil et al., Ewert et al., Zhang et al. and Yang et al. are discussed in detail above.
The combined references do not expressly teach ZIF-L. However, Gao et al. teaches that the ordinary artisan is aware that ZIF-L is a polymorph of ZIF-8 (Abstract), thus rendering them functional equivalents for the same purpose. It is then obvious to substitute the ZIF-8 of Liang et al., for the ZIF-L taught by Gao et al. with a reasonable expectation of success. "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(a).
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.
Response to Arguments: Applicant’s arguments filed 7/1/26 have been carefully considered but are not persuasive.
On page 8 of remarks, Applicant asserts: “The cited combination of references neither disclose nor suggest this specific combination of features.” Respectfully, the Examiner does not agree because in this art, optimizing the N:P ratio to between about 4 to about 10 is obvious in view of Zhang et al. and Yang et al. The ratio appears to be a common and conventional ratio to achieve high transfection efficiency with no criticality. The stability is an implicit property of the MOF shell encapsulating the lipid-nucleic acid complex composition as compared to a lipid-nucleic acid complex lacking the MOF shell.
On page 10 of remarks, Applicant submits that instantly amended claim 1 requires that a specific comparative stability outcome is demonstrated by the claimed composition and not merely to the presence of a MOF shell. This appears to be merely attorney argument unsubstantiated with any factual evidence. Especially when Liang et al. state: “the encapsulating framework advantageously provides a protective support for the bio-molecules. The protective capability of the framework is believed to derive from charge-based interactions between the framework and the guest bio-molecule, resulting in significant enhancement of the bio-molecule stability.” (Page 4, lines 4-7). Consequently, in view of the combined references there is a reasonable expectation of success. Only facts gleaned from the prior art have been employed by the Examiner. Hindsight bias has been avoided.
Respectfully, Applicant’s arguments filed 7/1/26 have been carefully considered but are not persuasive.
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 1, 2, 4, 5, 8-11, 15 and 16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 10947321 in view of Sharei et al. (US20180245089) and Herbert et al. (Nat Commun. 2021 Apr 13;12(1):13 pages) and Zhang et al. (CN109503411) and Yang et al. (Molecular Therapy: Nucleic Acids Vol. 19 March 2020; pages 1357-1367).
The method of producing MOF that encapsulates a biomolecule taught by the patent (Claim 1) includes oligonucleotides as the biomolecule (Examples 3 and 11) as well as modified forms (Column 18, lines 62-64) as well as ZIFs (Column 6, lines 18 -63). The scope of the MOF includes amorphous forms (Column 5, lines 27-29). MPEP 804: “The portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of that claim.” The patent also teaches that the product is in solution (Claims 1, 8 and 11) thus having an excipient of the solution present. The references of Sharei et al. and Herbert et al. are discussed above and incorporated by reference. While the patent does not expressly teach a lipid-nucleic acid (oligonucleotide) encapsulated within a MOF shell with the lipids claimed and the resulting stability functional parameters, the patent is open to inclusion of any biomolecule included modified nucleic acids. Sharei et al. teach and suggest lipid-nucleic acid complexes including oligonucleotides and the lipids claimed and Herbert et al. teach enhanced stability. It is simply selection of one alternative for another for the same purpose. “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). The patent does not expressly teach a N:P ratio of about 4 to about 10. However, the art of Zhang et al. and Yang et al., which are discussed above and those discussions are incorporated by references, guide the artisan to optimizing the N:P ratio to between about 4 to about 10 for efficient delivery of the oligonucleotide. The ordinary artisan would do so for the desirable efficient delivery. The patent does not expressly teach drying the composition but the ordinary artisan in this art would dry the composition to separate it from whatever solution was used to synthesize the composition. Consequently, the ordinary artisan performing the method of the patent would have a reasonable expectation of success in employing the lipid-nucleic acid complex of Sharie et al. in the method of the patent to produce a stabilized molecular delivery composition with the same stability functional parameters as claimed.
Claims 1, 2, 4, 5, 8-11 and 16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3 and 4 of U.S. Patent No. 11840580 in view of Sharei et al. (US20180245089) and Herbert et al. (Nat Commun. 2021 Apr 13;12(1):13 pages) and Zhang et al. (CN109503411) and Yang et al. (Molecular Therapy: Nucleic Acids Vol. 19 March 2020; pages 1357-1367). The scope of the crystalline MOF encapsulating a biomolecule such as a nucleic acid of the patent (Claims 1, 3 and 4) includes oligonucleotides (Examples 3 and 11) as well as modified forms (Column 19, lines 3-4) and ZIFs (Column 6, line 26 through column 7, line 3). MPEP 804: “The portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of that claim.” The references of Sharei et al. and Herbert et al. are discussed above and incorporated by reference. While the patent does not expressly teach a lipid-nucleic acid (oligonucleotide) encapsulated within a MOF shell with the lipids claimed and the resulting stability functional parameters, the patent is open to inclusion of any biomolecule included modified nucleic acids. Sharei et al. teach and suggest lipid-nucleic acid complexes including oligonucleotides and the lipids claimed and Herbert et al. teach enhanced stability. It is simply selection of one alternative for another for the same purpose. “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). The patent does not expressly teach a N:P ratio of about 4 to about 10. However, the art of Zhang et al. and Yang et al., which are discussed above and those discussions are incorporated by references, guide the artisan to optimizing the N:P ratio to between about 4 to about 10 for efficient delivery of the oligonucleotide. The ordinary artisan would do so for the desirable efficient delivery. The patent does not expressly teach adding excipients or drying the composition but the ordinary artisan in this art would dry the composition to separate it from whatever solution was used to synthesize the composition and when the composition is in solution the solution itself is an excipient. Consequently, the ordinary artisan performing the method of the patent would have a reasonable expectation of success in employing the lipid-nucleic acid complex of Sharie et al. in the method of the patent to produce a stabilized molecular delivery composition with the same stability functional parameters as claimed.
Response to Arguments:
Applicants assert that: “Sharei and Herbert do not disclose or suggest the specific combination of features recited in the presently claimed invention. In addition, Sharei and Herbert do not provide a reasonable expectation of success.” Respectfully, the Examiner has a different perspective. As explained previously, there is some degree of success expected when using cationic lipids. Especially in view of Zhang et al. who employ cationic lipids to make the drug delivery system to provide safe and high transfection efficiency. Furthermore, newly applied Zhang et al. and Yang et al. teach and suggest an N:P ratio of between about 4 to about 10. This is routinely optimized by the ordinary artisan in this art. Consequently, Applicant’s arguments are not persuasive at this time.
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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