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 .
Claim Status
Claims 1-12 are pending.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
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The foreign priority document is not in English. Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application. The effective filing date is then the international filing date of 12/23/2022.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 10/10/24, 8/22/25 and 1/13/26 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement are being considered by the examiner.
Drawings
New corrected drawings in compliance with 37 CFR 1.121(d) are required in this application because parts of Figures 1, 2 and 3 are too small to be legible. In figure 1, the legend on the right is not legible most likely due to small font size:
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In Figure 2, sections appear blurry (Examiner added arrows):
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In Figure 3 each panel contains on the lower left bottom a text string and the right side appears blurry:
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. Applicant is advised to employ the services of a competent patent draftsperson outside the Office, as the U.S. Patent and Trademark Office no longer prepares new drawings. The corrected drawings are required in reply to the Office action to avoid abandonment of the application. The requirement for corrected drawings will not be held in abeyance.
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.
Claim(s) 1-6 and 8 is/are rejected under 35 U.S.C. 102(a)(a) as being anticipated by Wang et al. (2012; IDS filed 8/22/25).
Regarding claims 1-5, Wang et al. disclose that “lipidoids with unsaturated oleyl tails are superior transfection agents compared to saturated lipidoids with n-octadecyl tails under the same conditions” (Abstract) and that compounds 8-I and 16-I can transfect cells with efficiency greater than 50% (Page 403, right column 2nd paragraph). Compounds 8-I and 16-I are derived from Figure 1:
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When C is (16), n is an integer from 1-6 and R’ is an unsaturated tail B) (I) having 18 carbon atoms -CH2)8-CH=CH-(CH2)7CH3, which is within 12-26 carbons. See MPEP 2131.03(I): “A SPECIFIC EXAMPLE IN THE PRIOR ART WHICH IS WITHIN A CLAIMED RANGE ANTICIPATES THE RANGE”.
Regarding claim 6, the claimed compound is disclosed by Wang et al. when C) is 8 (compound 8-I):
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Regarding claim 8, Wang et al. disclose a composition for drug delivery comprising the lipid of claim 1 (Figure 3A,B; Figure 6; Page 406: “In Vitro Gene Transfection. To facilitate high-throughput screening, the lipidoid/DNA or lipidoid/mRNA complexes were prepared simply by adding lipidoid to the sodium acetate buffer solutions (25 mM, pH = 5.5) of DNA or mRNA at ratios of 5:1 (w/w), followed by 15 min of incubation at room
temperature.”)
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 1-7 is rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (2012; IDS filed 8/22/25) and Van (US9526795).
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 genus of lipid compounds of Formula I and a method for preparing a lipid of formula 1:
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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 medicinal research chemist and such an educated artisan be knowledgeable of university level medicinal synthetic organic chemistry and have expertise in multi-step organic synthesis, purification and isolation of products.
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)
It is well settled that “a disclosure that anticipates under § 102 also renders the claim invalid under §103, for anticipation is the epitome of obviousness. See MPEP 1207.03(a)(II) states: “"lack of novelty is the epitome of obviousness." May, 574 F.2d at 1089, 197 USPQ at 607 (citing In re Pearson, 494 F.2d 1399, 1402, 181 USPQ 641, 644 (CCPA 1974))”. Accordingly, the claims rejected under §102 above are also invalid under §103. As discussed above, Wang et al. teach and suggest a claimed compound of Formula I and suggest screening the compounds as transfection agents (Abstract; Page 404, top left column; Figure 2; page 406, In Vitro Gene Transfection). With regard to the synthesis Wang et al. teach: “Compounds in the library were synthesized and characterized as previously described by our group as well as several others.” (Page 406, Methods).
Another way of arriving at the claimed compound is provided by Van et al. Van et al. teach methods of protecting an amine and reaction with methyl acrylate to produce a protected methyl ester (Column 84, Example 1):
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The protected methyl ester is then treated with an amine to product a dendrimer in Example 2:
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Van teaches deprotection (Column 78, lines 48-5; column 79, lines 1-35).
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 Wang et al. is that Wang et al. do not expressly teach the claimed steps to produce all the claimed lipids of Formula I. This deficiency in Wang et al. is cured by the teachings of Van.
1. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to react a protected compound with methyl acrylate to obtain a compound that is further treated with an unsaturated amine having 12-26 carbons and deprotection to obtain the lipids of Formula 1, as suggested by Van, and produce the instant invention.
One of ordinary skill in the art would have been motivated to do this because it is merely another synthetic route to the same product where the ordinary organic synthetic chemist artisan would employ the corresponding unsaturated amine with 12-26 carbons, such as palmitoleylamine (C16-NH2) or oleylamine (C18-NH2), to react or sequentially react with the protected methyl ester compound to produce the amide through nucleophilic acyl substitution with the same or combination of unsaturated chains such that R1 and R2 of Formula 1 can be independently selected with a reasonable expectation of success. Deprotection to yield the claimed compound is the next logical step for the synthetic organic chemist. Employing this rationale synthetic design to obtain the claimed product, it is then obvious to vary n from 1-6 and the chain length of 12-26 carbons for the unsaturated hydrocarbon group(s) to build a library of lipids for screening. These are conventional synthetic steps for the synthetic organic chemist without any undue experimentation required. Accordingly, the ordinary artisan in this art would have a reasonable expectation of success in performing the claimed method steps to arrive at the claimed compounds in the absence of evidence to the contrary.
Claims 9-12 are rejected under 35 U.S.C. 103 as being unpatentable over Nguyen et al. (US20120009222; IDS filed 10/10/2024) and Wang et al. (2012; IDS filed 8/22/25) and Seo et al. (US20110257253).
Applicant claims:
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Nguyen et al. teach: “The lipidoids of the present invention may also be used to form drug delivery devices. The lipidoids may be used to encapsulate agents including polynucleotides. The inventive lipidoids have several properties that make them particularly suitable in the preparation of drug delivery devices. These include 1) the ability of the lipid to complex and “protect’ labile polynucleotides; 2) the ability to buffer the pH in the endosome; 3) the ability to act as a “proton sponge' and cause endosomolysis; and 4) the ability to neutralize the charge on negatively charged polynucleotides. In certain embodiment, the lipidoids are used to form nanoparticles containing the polynucleotides to be delivered. These nanoparticles may include other materials such as proteins, carbohydrates, synthetic polymers (e.g., PEG, PLGA), lipids, and natural polymers.” [0224] Nguyen et al. teach: “Once the complex or particles have been prepared, they may be combined with one or more pharmaceutical excipients to form a pharmaceutical composition that is suitable to administer to animals including humans.” [0235] Thus, pharmaceutical compositions for drug delivery comprising the encapsulated lipids/lipidoids in amphiphilic PLGA is suggested by Nguyen et al.
As discussed above, Wang et al. teach the claimed lipids of Formula I.
Seo et al. teach adding a salt of polylactic acid to nanoparticle compositions comprising an amphiphilic block copolymer polylactic-co-glycolide (Claims 1-2 and 9). Seo et al. teach: “The salt of polylactic acid or polylactic acid derivative, whose carboxylic acid end is bound to an alkali metal ion, is added to the micelles formed of the amphiphilic block copolymer to harden the inner parts of the micelles, and thus improves the drug encapsulation efficiency within the micelles.” [0037]
The difference between the instant application and Nguyen et al. is that Nguyen et al. do not expressly teach a composition with the lipid compounds claimed or adding a salt of polylactic acid to the composition. This deficiency in Nguyen et al. is cured by the teachings of Wang et al. and Seo et al.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Nguyen et al. with the lipidoids of Wang et al. and the salt of polylactic acid of Seo et al. and produce the instant invention.
One of ordinary skill in the art would have been motivated to do this because Nguyen et al. teach and suggest nanoparticles of the lipidoids as drug delivery devices in combination with amphiphilic block copolymer PLGA and it is merely substituting functionally equivalent lipidoids of Wang et al. into the nanoparticles of Nguyen et al. to produce drug delivery vehicles of the lipidioids claimed and amphiphilic block copolymer where the lipid/lipidoid forms a complex and is encapsulated in the nanoparticle structure by the amphiphilic block copolymer. "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). Furthermore, the ordinary artisan is motivated to add a salt of polylactic acid to the drug-containing nanoparticle to encapsulate the lipid/lipidoid drug complex for the beneficial property of improving drug encapsulation efficiency as taught by Seo et al. Thus, a composition for drug delivery comprising the claimed drug-containing lipid nanoparticles encapsulated in a nanoparticle structure formed by an amphiphilic block copolymer and a salt of polylactic acid is obvious in view of the combined references. The ordinary artisan would do so with a reasonable expectation of success.
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 1-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of copending Application No. 18722663. Although the claims at issue are not identical, they are not patentably distinct from each other because copending has common inventors and the same assignee and is directed to the same lipids, synthesis and drug-containing nanoparticles compositions comprising an amphiphilic block copolymer and a salt of polylactic acid as shown in claims 1-8 below:
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Accordingly, the ordinary artisan would have recognized the obvious variation of the instantly claimed subject matter over the copending subject matter.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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