DETAILED ACTION
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 .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Abbreviations and Claim Interpretation
The abbreviation “NLC” in claim 100 is understood by the examiner to refer to “nanostructured lipid carrier.” The examiner notes that the instant specification discloses that nanostructured lipid carriers have a core comprising a combination of liquid-phase lipids and solid-phase lipids on page 22, paragraph 0065. Nevertheless, this is understood to be a description of the fact that the nanostructured lipid carrier described in the instant specification has this feature and is not understood to be a definition of the phrase “nanostructured lipid carrier.” It is improper to import claim limitations from the specification; see MPEP 2111.01(II).
For the purposes of examination under prior art, the examiner will examine the phrase “nanostructured lipid carrier” as being drawn to a nanoparticle comprising lipids. While the term “nano” in “nanostructured is not believed to limit the size range, the examiner will nevertheless search for particles sized in the 1-1000 nm size range.
Claim Rejections - 35 USC § 112(b) – Indefiniteness
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 101 and 144-154 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.
Description of examples or preferences is properly set forth in the specification rather than the claims. If stated in the claims, examples and preferences may lead to confusion over the intended scope of a claim. In those instances where it is not clear whether the claimed narrower range is a limitation, a rejection under 35 U.S.C. 112(b) should be made. See MPEP 2173.05(d) and 2173.05(c).
Claim 101 recites the following:
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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 101 recites the broad recitations of a cationic component, a hydrophobic surfactant, and a surfactant, and the claim also recites a cationic lipid, a sorbitan ester, and a hydrophilic surfactant, 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.
The examiner also notes here that as claim 101 recites a hydrophobic surfactant and a surfactant as a separate component, it is unclear whether prior art teaching a hydrophobic surfactant but no second surfactant reads on the claim requirements of both (c) and (d), or whether the claim requires that the surfactant in (d) is a separate material from that in (c).
For the purposes of examination under prior art, the examiner will examine the claim as if (b) requires any cationic component, (c) requires a hydrophobic surfactant, and (d) requires a second surfactant different from that in (c).
Claims 138-140 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.
Claim 138 recites the following, which is reproduced below with annotation by the examiner.
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It is unclear how the term “to” further limits the claims, thereby rendering claim 138 indefinite.
For the purposes of examination under prior art, the examiner will understand claim 138 a nitrogen to phosphate ratio in the prior art reads on this claim requirement.
Claim Rejections - 35 USC § 103 – Obviousness
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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 100 and 137-143 is/are rejected under 35 U.S.C. 103 as being unpatentable over Brito et al. (US 2012/0156251 A1).
Brito et al. (hereafter referred to as Brito) is drawn to cationic oil in water emulsions used to deliver an RNA molecule encoding an antigen, as of Brito, title and abstract. Brito teaches the following, as of paragraphs 0210-0211, reproduced below.
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As such, Brito appears to teach optimizing the N/P of a composition comprising particles delivering RNA to optimize expression of said RNA. The N/P ratio refers to the molar ratio of nitrogen in the cationic lipid in the particle to phosphorus in the RNA, as explained by paragraph 0210 of Brito.
As to claim 100, it is the examiner’s position that Brito is not anticipatory because
although the cationic lipid concentration is an essential element of the lipid nanoparticle, it is not the entirety of the particle; as such, the N/P ratio is not necessarily the same as the molar ratio of the bioactive agent to the NLC; and
Brito teaches optimizing to increase expression of the encoded protein, rather than to increase antibody titer.
Nevertheless, as to claim 100, Brito teaches cationic lipid in particular amounts; see e.g. the entirety of page 14 of Brito. As such, the skilled artisan would have expected that optimization of the N/P ratio would have resulted in optimization of the ratio of bioactive agent to particle.
Also as to claim 100, Brito teaches eliciting an antibody mediated immune response, as well as other forms of immune response, to provide protection to an immunized host, as of the end of paragraph 0095 of Brito. Brito teaches induction of B-cell production of antibodies specific for an antigen of interest in paragraph 0248. Brito appears to desire increased antibody response in paragraph 0380, as Brito teaches that the use of the cationic nanoemulsion results in increased antibody titer as compared with naked RNA. In view of at least these passages, the skilled artisan would have been motivated to have optimized the antibody titer in view of the teachings of Brito.
As to claim 100, the claim recites the abbreviation “NLC.” This refers to a nanostructured lipid carrier. The examiner understands the emulsion particles of Brito, abstract, to read on this requirement. The particles of Brito are sized from about 80 nm to 180 nm, as of paragraph 0032 of Brito, which is sufficient to render the particles of Brito to be in the nanosize range. The particles of Brito also comprise lipids, rendering them to be lipidic carriers. As such, the particles of Brito are understood to read on the required nanostructured lipidic carriers. See the section above entitled “Abbreviations and Claim Interpretation.”
As to claim 137, Brito teaches RNA in the abstract, which reads on the required nucleic acid.
As to claim 138, Brito teaches an N/P ratio in paragraphs 0210-0211.
As to claims 139-140, Brito teaches an N/P ratio of about 1:1 in paragraph 0210, which is within the range required by these claims.
As to claim 141, Brito teaches RNA as a bioactive agent in the abstract. Brito also teaches that negatively charged molecule and cationic lipid in the emulsions may be adjusted or optimized to provide desired strength of binding and binding capacity, as of paragraph 0209. As the negatively charged molecule is RNA, this would have resulted in providing an interpretation of RNA binding to the particle carrier. Brito also teaches interpreting in vitro expression of a RNA-encoded protein as of at least paragraph 0211.
As to claim 142, Brito teaches measuring neutralization antibody titers as of at least paragraph 0379.
As to claim 143, Brito teaches contacting nucleic acids with host cells, as of at least paragraph 0212.
Claims 100-101 and 137-143 is/are rejected under 35 U.S.C. 103 as being unpatentable over Brito et al. (US 2012/0156251 A1) in view of Naseri et al. (Advanced Pharmaceutical Bulletin, Vol. 5(3), 2015, pages 305-313).
Brito is drawn to a cationic oil in water emulsion for vaccine delivery, as of the title and abstract. Brito teaches a combination of squalene, DOTAP, RNA, Tween 80 and Span 85, as of paragraph 0106. See the rejection above over Brito by itself.
For the purposes of this rejection, it is assumed, purely en arguendo and regarding this ground of rejection only, that Brito does not teach a liquid lipid and a solid lipid in the same composition.
Naseri et al. (hereafter referred to as Naseri) is drawn to solid lipid nanoparticles and nanostructured lipid carriers, as of page 305, title and abstract. Naseri teaches these two types of drug delivery vehicles as an alternative to emulsions (as well as liposomes and polymeric nanoparticles), as of Naseri, page 305, paragraph bridging left and right columns. Naseri teaches that nanostructured lipidic carriers, which are abbreviated as NLCs, have improved stability, loading capacity, and prevent drug expulsion during storage, as of Naseri, page 305, right column, bottom paragraph. Naseri also teaches that these NLCs comprise both solid and liquid lipids. See also Naseri, page 307, figure 3(III), which teaches a particle with both oil (e.g. liquid lipid) and solid lipid therein.
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Naseri is not anticipatory because, while Naseri teaches cationic solid lipid nanoparticles on page 309, right column, (which lack a liquid lipid), Naseri does not teach cationic NLCs which comprise both a solid and liquid lipid and also a cationic ingredient. The examiner notes the above-reproduced figure from Naseri does not include a cationic ingredient.
It would have been prima facie obvious for one of ordinary skill in the art to have modified the composition of Brito to have included a solid lipid along with the liquid lipid to have been a nanostructured lipidic carrier, as taught by Naseri, rather than an emulsion. Brito is drawn to a cationic oil in water emulsion for delivery of a negatively charged nucleic acid active agent. Naseri is drawn to nanostructured lipidic carriers which have a core comprising a solid lipid combined with a liquid lipid, as opposed to only a liquid in Brito. Naseri teaches that these compositions which have a liquid and solid lipid together have improved stability, loading capacity, and prevent drug expulsion during storage, as of Naseri, page 305, right column, bottom paragraph. As such, the skilled artisan would have been motivated to have modified Brito to have further included a solid lipid and to have been a nanostructured lipid carrier rather than an emulsion to have created a composition that would have predictably had good stability and good loading capacity with a reasonable expectation of success.
As to claim 100, the rationale provided above in the rejection over Brito by itself also applies to the rejection over the combination of Brito in view of Naseri. With that being said, Naseri teaches the required nanostructured lipidic carrier.
As to claim 101, Brito teaches the following, all in paragraph 0334:
Brito teaches squalene in paragraph 0334, wherein this is a liquid lipid;
Brito teaches DOTAP in paragraph 0334, wherein this is a cationic lipid;
Brito teaches Span 85 in paragraph 0334, wherein this is a hydrophobic surfactant;
Brito teaches Tween 80 in paragraph 0334, wherein this is a hydrophilic surfactant.
Brito differs from the composition of claim 101 because Brito does not teach the required solid phase lipid, wherein the required solid phase lipid appears to be other than the cationic lipid. However, Naseri teaches combining a solid and liquid phase lipid as of at least page 306, left column, top paragraph.
As to claim 137, Brito teaches RNA in the abstract, which reads on the required nucleic acid.
As to claim 138, Brito teaches an N/P ratio in paragraphs 0210-0211.
As to claims 139-140, Brito teaches an N/P ratio of about 1:1 in paragraph 0210, which is within the range required by these claims.
As to claim 141, Brito teaches RNA as a bioactive agent in the abstract. Brito also teaches that negatively charged molecule and cationic lipid in the emulsions may be adjusted or optimized to provide desired strength of binding and binding capacity, as of paragraph 0209. As the negatively charged molecule is RNA, this would have resulted in providing an interpretation of RNA binding to the particle carrier. Brito also teaches interpreting in vitro expression of a RNA-encoded protein as of at least paragraph 0211.
As to claim 142, Brito teaches measuring neutralization antibody titers as of at least paragraph 0379.
As to claim 143, Brito teaches contacting nucleic acids with host cells, as of at least paragraph 0212.
Claims 144-146 and 153 is/are rejected under 35 U.S.C. 103 as being unpatentable over Brito et al. (US 2012/0156251 A1) in view of Naseri et al. (Advanced Pharmaceutical Bulletin, Vol. 5(3), 2015, pages 305-313), the combination further in view of Lobovkina et al. (US 2013/0243848 A1).
Brito is drawn to a cationic oil in water emulsion for vaccine delivery, as of the title and abstract. Brito teaches a combination of squalene, DOTAP, RNA, Tween 80 and Span 85, as of paragraph 0106. Naseri teaches adding a solid lipid with a liquid lipid in the core. See the rejection above over Brito in view of Naseri by themselves. Naseri further teaches triglycerides in nanostructured lipid carriers as of page 307, right column, with certain terms highlighted by the examiner.
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Naseri does not teach trimyristin.
Lobovkina et al. (hereafter referred to as Lobovkina) is drawn to a lipid nanoparticle for delivering siRNA, as of Lobovkina, figure in abstract, reproduced below.
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Lobovkina teaches trimyristin in the core, as of Lobovkina, paragraphs 0040 and 0055.
Lobovkina differs from the claimed invention because Lobovkina does not appear to teach a liquid lipid in the core. Also, Lobovkina appears to teach that the nucleic acid is encapsulated, rather than on the outside, as required by instant claim 2.
It would have been prima facie obvious for one of ordinary skill in the art to have combined the squalene of Brito and the trimyristin of Lobovkina to have been included in the core of the particle of Brito. Naseri teaches that nanostructured lipidic carriers comprise a liquid lipid and solid lipid in the core, and have advantages of improving stability, improving loading capacity, and preventing drug expulsion during storage. Naseri also teaches triglycerides as solid lipids to be used in nanostructured lipidic carriers. As such, in order to achieve the above-indicated benefits, the skilled artisan would have been motivated to have combined the trimyristin of Lobovkina (which would have been known to have been a triglyceride) with the composition of Brito to have formed a cationic lipid nanoparticle predictably capable of delivering a nucleic acid cargo with a reasonable expectation of success.
As to claim 144, Lobovkina teaches trimyristin in the core, as of Lobovkina, paragraphs 0040 and 0055.
As to claim 145, Brito teaches squalene as of paragraph 0334.
As to claim 146, Brito teaches DOTAP as of paragraph 0334. The examiner notes here that DOTAP is a well-known acronym which refers to 1,2-dioleoyl-3-triethylammoniumpropane; see paragraph 0332 of Brito.
As to claim 153, Brito provides teachings regarding secreted alkaline phosphatase expression, as of Brito, at least paragraphs 0353-0354 and 0362. Brito also teaches a N:P molar ratio of about 15:1, as of paragraph 0210. In view of this, the skilled artisan would have been motivated to have optimized both the SEAP expression and the N:P molar ratio of Brito to have achieved the claimed method.
Claims 147-152 is/are rejected under 35 U.S.C. 103 as being unpatentable over Brito et al. (US 2012/0156251 A1) in view of Naseri et al. (Advanced Pharmaceutical Bulletin, Vol. 5(3), 2015, pages 305-313), the combination further in view of Lobovkina et al. (US 2013/0243848 A1), the combination further in view of Collin-Djangone et al. (US 2007/0003501 A1).
Brito is drawn to a cationic oil in water emulsion for vaccine delivery, as of the title and abstract. Brito teaches a combination of squalene, DOTAP, RNA, Tween 80 and Span 85, as of paragraph 0106. Naseri teaches adding a solid lipid with a liquid lipid in the core. Lobovkina teaches trimyristin. See the rejection above over Brito in view of Naseri and Lobovkina by themselves.
None of the above references teach sorbitan monostearate.
Collin-Djangone et al. (hereafter referred to as Collin) is drawn to cationic particles comprising double stranded RNA, as of Collin, title and abstract. The composition of Collin may include sorbitan monostearate, as of Collin, at least paragraph 0085.
Collin differs from the claimed invention because Collin is drawn to delivery of double stranded RNA, which does not encode for an antigen. As such, the skilled artisan would not have been motivated to have optimized antibody titers because no antigen against which antibodies are desired is encoded by the RNA.
It would have been prima facie obvious for one of ordinary skill in the art to have combined the sorbitan monostearate of Collin with the particle of Brito. Brito is drawn to a method of forming a cationic particle comprising RNA, and this particle may include a surfactant. While Brito does not teach sorbitan monostearate, Collin teaches that sorbitan monostearate may be included in a particle used for the delivery of nucleic acid. As such, the skilled artisan would have been motivated to have included the sorbitan monostearate surfactant of Collin in the particle made by the method of Brito for predictable formation of a particle used for delivery of nucleic acid with a reasonable expectation of success. Generally, it is prima facie obvious to select a known material (sorbitan monostearate is a known material, as of Collin) for incorporation into a composition (that made by the method of Brito), based on its recognized suitability for its intended use (stabilizing a cationic emulsion for delivery of a nucleic acid). See MPEP 2144.07.
As to claim 147, the sorbitan monostearate of Collin, paragraph 0085 is understood to read on the requirements of this claim.
As to claim 148, Brito teaches polysorbate 80 (also known as Tween 80) as of at least paragraph 0020.
As to claim 149, Brito teaches the following, as of paragraph 0207, reproduced in part below.
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In view of the above teachings, the examiner takes the position that Brito teaches that the bioactive agent (e.g. the negatively charged molecule, which is a nucleic acid as of the abstract of Brito) is associated with the particle of the cationic oil in water emulsion of Brito.
As to claim 150, Brito teaches RNA in the abstract.
As to claim 151, Brito teaches 0.5% DOTAP (a cationic lipid) and 0.5% Tween 80 (a hydrophilic surfactant) in paragraph 0285; this results in a 1:1 ratio of these ingredients.
As to claim 152, Brito teaches the following as of paragraph 0285, relevant text reproduced below.
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Naseri teaches solid fat (i.e. solid lipid) in concentrations as low as 0.1% and as high as 30% as of page 306, left column. These amounts are not the same as what is required by the instant claims. Nevertheless, generally, differences in concentration between the claimed invention and prior art will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. See MPEP 2144.05(II)(A). In this case, no evidence of criticality has been provided by applicant to the file record. Additionally, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP 2144.05(II)(A). In this case, the general conditions of a particle comprising liquid phase lipid, solid phase lipid, cationic lipid, sorbitan ester (as a hydrophobic surfactant) and hydrophilic surfactant (e.g. polysorbate or Tween) has been taught by the prior art. As such, it would not have been inventive for the skilled artisan to have discovered the optimum or workable ranges of these materials via routine experimentation.
Claims 154 is/are rejected under 35 U.S.C. 103 as being unpatentable over Brito et al. (US 2012/0156251 A1) in view of Naseri et al. (Advanced Pharmaceutical Bulletin, Vol. 5(3), 2015, pages 305-313), the combination further in view of Lobovkina et al. (US 2013/0243848 A1), the combination further in view of Chahal et al. (Scientific Reports, Vol. 7:252, 2017, pages 1-9 and 8 pages of supplemental information).
Brito is drawn to a cationic oil in water emulsion for vaccine delivery, as of the title and abstract. Brito teaches a combination of squalene, DOTAP, RNA, Tween 80 and Span 85, as of paragraph 0106. Naseri teaches adding a solid lipid with a liquid lipid in the core. Lobovkina teaches trimyristin. See the rejection above over Brito in view of Naseri and Lobovkina by themselves. The payload of Brito appears to comprise an RNA which may include a Venezuelan equine encephalitis virus for self-replication as well as a material to be replicated, as of Brito, paragraph 0225.
Chahal et al. (hereafter referred to as Chahal) is drawn to an RNA nanoparticle vaccine against Zika virus, as of Chahal, page 1, title and abstract. This nanoparticle is an RNA comprising a Venezuelan equine encephalitis virus for self-replication, as of Chahal, page 6, relevant text reproduced below.
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This appears to be a self-amplifying RNA vaccine, which reads on the required rvRNA (i.e. replicating viral RNA).
Chahal does not teach the required lipids and surfactants.
It would have been prima facie obvious for one of ordinary skill in the art to have used the nanoparticle of Brito in view of Naseri and Lobovkina to have delivered the RNA vaccine of Chahal. Brito is drawn to a nanoparticle composition that may be used to deliver a variety of nucleic acid active agents including nucleic acid vaccines, and appears to specify self-amplifying RNA vaccines encoding both an antigen as well as self-replicating machinery from a Venezuelan equine encephalitis virus. The composition of Chahal is a self-replicating RNA vaccine. As such, the skilled artisan would have been motivated to have used the particle of Brito in view of Naseri and Lobovkina to have predictably delivered the RNA vaccine of Chahal in a manner that it predictably expresses the Zika antigen and that an immune response is predictably formed against the Zika antigen with a reasonable expectation of success.
As to claim 154, the claim requires a particular antibody titer. Chahal does not appear to specify this in the same units as required by the instant claims. Nevertheless, the skilled artisan would have expected that the nanoparticle of Brito, as modified by Naseri and Lobovkina, would have predictably resulted in achieving the required antibody titer because the delivery vehicle would have improved expression due to the presence of cationic lipid aiding in intracellular delivery with a reasonable expectation of success, thereby resulting in sufficient antigen formation that an antibody response against said antigen would have been predictably elicited with a reasonable expectation of success.
Note Regarding Reference Date: The instant application appears to have an earliest effective filing date of 15 June 2017. Chahal was published on 21 March 2017, which is less than one year earlier than the earliest effective filing date. As such, Chahal is prior art under AIA 35 U.S.C. 102(a)(1). There is no evidence of common inventorship between Chahal and the instant application; as such, the exceptions under AIA 35 U.S.C. 102(b)(1)(A) and 102(b)(1)(B) would not appear to be applicable.
Claim Rejections - 35 USC § 101 – Subject Matter Eligibility
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 100-101 and 137-154 are rejected under 35 U.S.C. 101 because the claimed invention is directed to the judicial exception of an abstract idea without significantly more. The examiner presents the following rationale in support of this position.
MPEP 2105 presents the following flow-chart for determining subject matter eligibility.
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Step 2A is further broken into the following two prongs
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As such, the examiner takes the following position regarding the above indicated steps.
Regarding Step 1: Regarding step 1, the instant claims are drawn to a process.
Regarding Step 2A Prong 1: The instant claims recite “selecting a molar ratio.” The examiner best understands this to be drawn to an abstract idea because this selection occurs only in the human mind.
Regarding Step 2A Prong 2: Instant claim 100 does not integrate the abstract idea into a practical application. Instant claim 101, while providing further information about the materials selected, does not integrate the abstract idea into a practical application. This is at least because, while claim 101 further limits the particle formed, it does not further limit the method steps by which the particle is formed.
Regarding Step 2B: The examiner best understands that the claims fail to recite additional elements that amount to significantly more than the abstract idea. The components recited by claim 101 do not amount to significantly more than the judicial exception because the instant claims, while reciting that the components are in the final product, do not actually recite adding these components to form a final product. In view of the failure of the claims to recite this feature, the additional components of claim 101 fail to amount to significantly more than the judicial exception.
The examiner further notes here that all of the elements of claim 101 with the exception of the solid phase lipid are taught by Brito et al. (US 2012/0156251 A1), as explained in the prior art rejection above. Therefore, these elements do not appear to be markedly different. Furthermore, the solid phase lipid has been combined with a liquid phase lipid to form a lipid nanoparticle as taught by Lobovkina et al. (US 2013/0243848 A1), as explained in the prior art rejection above. Therefore, the solid phase lipid also does not appear to be markedly different.
Additionally, regarding claim 141, the limitation “using the N to P ratio to provide an interpretation of RNA-NLC binding and corresponding in vitro expression of a RNA-encoded protein” appears to be drawn to an abstract idea without significantly more, and itself results in an additional issue regarding subject matter eligibility.
Non-Statutory 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 100-101 and 137-153 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 11,141,377 in view of Brito et al. (US 2012/0156251 A1).
Claim 154 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 11,141,377 in view of Brito et al. (US 2012/0156251 A1), the combination further in view of Chahal et al. (Scientific Reports, Vol. 7:252, 2017, pages 1-9 and 8 pages of supplemental information).
The instant claims are drawn to a method of optimizing delivery of a bioactive agent to a cell comprising selecting a particular molar ratio of ingredients. The material being delivered to the cell appears to be a nanostructured lipidic carrier comprising a nucleotide that encodes an antigen. The nanostructured lipidic carrier comprises an oil core with a solid and liquid phase lipid, a cationic component a hydrophobic surfactant, and a second surfactant that may be hydrophilic, as of claim 101.
The conflicting claims are drawn to a composition comprising a lipid particle containing squalene (a liquid lipid), trimyristin (a solid lipid), DOTAP (a cationic lipid), sorbitan monostearate (a hydrophobic surfactant), and polysorbate 80 (a hydrophilic surfactant). These are used to deliver a bioactive agent which is an RNA or DNA, and may encode various antigens, as of conflicting claims 7 and 13. The conflicting claims also recite method of making this composition as well as methods of administering this composition to generate an immune response.
The conflicting claims do not recite optimization of the amounts of ingredients.
Brito et al. (hereafter referred to as Brito) is drawn to cationic oil in water emulsions used to deliver an RNA molecule encoding an antigen, as of Brito, title and abstract. Brito teaches the following, as of paragraphs 0210-0211, reproduced in the obviousness rejection above. As such, Brito appears to teach optimizing the N/P of a composition comprising particles delivering RNA to optimize expression of said RNA. The N/P ratio refers to the molar ratio of nitrogen in the cationic lipid in the particle to phosphorus in the RNA, as explained by paragraph 0210 of Brito.
It would have been prima facie obvious for one of ordinary skill in the art to have optimized the amounts and/or concentrations of ingredients in the composition of the conflicting claims and the composition used in the method of the conflicting claims. The conflicting claims are drawn to a composition and method for administering a bioactive agent that is RNA that encodes an antigen. The composition of the conflicting claims has essentially the same ingredients as that recited by instant claim 101. The teachings of Brito would have motivated the skilled artisan to have optimized the amounts and concentrations of various ingredients in order to have predictably improved gene expression with a reasonable expectation of success.
As to claim 154, the composition and method of the conflicting claims comprise a nucleic acid active agent that encodes an antigen in vivo. Chahal teaches a nucleic acid which encodes the Zika antigen. As such, the skilled artisan would have been motivated to have predictably delivered the RNA of Chahal with the nanoparticle of the conflicting claims with a reasonable expectation that doing so would have successfully resulted in expression of the Zika antigen and successfully would have resulted in an antibody response against said antigen.
Claims 100-101 and 137-153 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-49 of U.S. Patent No. 12,201,722 in view of Brito et al. (US 2012/0156251 A1).
Claim 154 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-49 of U.S. Patent No. 12,201,722 in view of Brito et al. (US 2012/0156251 A1), the combination further in view of Chahal et al. (Scientific Reports, Vol. 7:252, 2017, pages 1-9 and 8 pages of supplemental information).
The instant claims are drawn to a method of optimizing delivery of a bioactive agent to a cell comprising selecting a particular molar ratio of ingredients. The material being delivered to the cell appears to be a nanostructured lipidic carrier comprising a nucleotide that encodes an antigen. The nanostructured lipidic carrier comprises an oil core with a solid and liquid phase lipid, a cationic component a hydrophobic surfactant, and a second surfactant that may be hydrophilic, as of claim 101.
The conflicting claims are drawn to a composition comprising a lipid particle containing a liquid lipid, a solid lipid that is trimyristin, a cationic lipid, and a hydrophilic surfactant. These are used to deliver a bioactive agent which is an RNA or DNA, and may encode various antigens, as of conflicting claims 4, 11, 16, and 24. The conflicting claims also recite method of making this composition.
The conflicting claims do not recite optimization of the amounts of ingredients.
Brito et al. (hereafter referred to as Brito) is drawn to cationic oil in water emulsions used to deliver an RNA molecule encoding an antigen, as of Brito, title and abstract. Brito teaches the following, as of paragraphs 0210-0211, reproduced in the obviousness rejection above. As such, Brito appears to teach optimizing the N/P of a composition comprising particles delivering RNA to optimize expression of said RNA. The N/P ratio refers to the molar ratio of nitrogen in the cationic lipid in the particle to phosphorus in the RNA, as explained by paragraph 0210 of Brito.
It would have been prima facie obvious for one of ordinary skill in the art to have optimized the amounts and/or concentrations of ingredients in the composition of the conflicting claims and the composition used in the method of the conflicting claims. The conflicting claims are drawn to a composition and method for administering a bioactive agent that is RNA that encodes an antigen. The composition of the conflicting claims has essentially the same ingredients as that recited by instant claim 101. The teachings of Brito would have motivated the skilled artisan to have optimized the amounts and concentrations of various ingredients in order to have predictably improved gene expression with a reasonable expectation of success.
As to claim 154, the composition and method of the conflicting claims comprise a nucleic acid active agent that encodes an antigen in vivo. Chahal teaches a nucleic acid which encodes the Zika antigen. As such, the skilled artisan would have been motivated to have predictably delivered the RNA of Chahal with the nanoparticle of the conflicting claims with a reasonable expectation that doing so would have successfully resulted in expression of the Zika antigen and successfully would have resulted in an antibody response against said antigen.
Claims 100 and 137-143 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 12,350,329 in view of Brito et al. (US 2012/0156251 A1).
The instant claims are drawn to a method of optimizing delivery of a bioactive agent to a cell comprising selecting a particular molar ratio of ingredients. The material being delivered to the cell appears to be a nanostructured lipidic carrier comprising a nucleotide that encodes an antigen. The nanostructured lipidic carrier comprises an oil core with a solid and liquid phase lipid, a cationic component a hydrophobic surfactant, and a second surfactant that may be hydrophilic, as of claim 101.
The conflicting claims are drawn to a composition comprising a lipid particle containing a liquid lipid, a cationic lipid, a hydrophilic surfactant, and a hydrophobic surfactant. These are used to deliver a bioactive agent which is an RNA or DNA, and encode an influenza antigen.
The conflicting claims do not recite optimization of the amounts of ingredients.
Brito et al. (hereafter referred to as Brito) is drawn to cationic oil in water emulsions used to deliver an RNA molecule encoding an antigen, as of Brito, title and abstract. Brito teaches the following, as of paragraphs 0210-0211, reproduced in the obviousness rejection above. As such, Brito appears to teach optimizing the N/P of a composition comprising particles delivering RNA to optimize expression of said RNA. The N/P ratio refers to the molar ratio of nitrogen in the cationic lipid in the particle to phosphorus in the RNA, as explained by paragraph 0210 of Brito.
It would have been prima facie obvious for one of ordinary skill in the art to have optimized the amounts and/or concentrations of ingredients in the composition of the conflicting claims and the composition used in the method of the conflicting claims. The conflicting claims are drawn to a composition and method for administering a bioactive agent that is RNA that encodes an antigen. The composition of the conflicting claims has essentially the same ingredients as that recited by instant claim 101. The teachings of Brito would have motivated the skilled artisan to have optimized the amounts and concentrations of various ingredients in order to have predictably improved gene expression with a reasonable expectation of success.
Claims 100 and 137-143 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 12,257,299 in view of Brito et al. (US 2012/0156251 A1).
The instant claims are drawn to a method of optimizing delivery of a bioactive agent to a cell comprising selecting a particular molar ratio of ingredients. The material being delivered to the cell appears to be a nanostructured lipidic carrier comprising a nucleotide that encodes an antigen. The nanostructured lipidic carrier comprises an oil core with a solid and liquid phase lipid, a cationic component a hydrophobic surfactant, and a second surfactant that may be hydrophilic, as of claim 101.
The conflicting claims are drawn to a composition comprising a lipid particle containing a liquid lipid, a cationic lipid, a hydrophilic surfactant, and a hydrophobic surfactant. These are used to deliver a bioactive agent which is an RNA or DNA, and encode a SARS-CoV-2 (i.e. COVID-19) antigen.
The conflicting claims do not recite optimization of the amounts of ingredients.
Brito et al. (hereafter referred to as Brito) is drawn to cationic oil in water emulsions used to deliver an RNA molecule encoding an antigen, as of Brito, title and abstract. Brito teaches the following, as of paragraphs 0210-0211, reproduced in the obviousness rejection above. As such, Brito appears to teach optimizing the N/P of a composition comprising particles delivering RNA to optimize expression of said RNA. The N/P ratio refers to the molar ratio of nitrogen in the cationic lipid in the particle to phosphorus in the RNA, as explained by paragraph 0210 of Brito.
It would have been prima facie obvious for one of ordinary skill in the art to have optimized the amounts and/or concentrations of ingredients in the composition of the conflicting claims and the composition used in the method of the conflicting claims. The conflicting claims are drawn to a composition and method for administering a bioactive agent that is RNA that encodes an antigen. The composition of the conflicting claims has essentially the same ingredients as that recited by instant claim 101. The teachings of Brito would have motivated the skilled artisan to have optimized the amounts and concentrations of various ingredients in order to have predictably improved gene expression with a reasonable expectation of success.
Claims 100 and 137-143 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-31 of U.S. Patent No. 11,679,163 in view of Brito et al. (US 2012/0156251 A1).
Claims 100 and 137-143 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 11,433,142 in view of Brito et al. (US 2012/0156251 A1).
Claims 100 and 137-143 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 11,648,321 in view of Brito et al. (US 2012/0156251 A1).
Claims 100 and 137-143 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-40 of U.S. Patent No. 11,654,200 in view of Brito et al. (US 2012/0156251 A1).
Claims 100 and 137-143 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-33 of U.S. Patent No. 11,752,218 in view of Brito et al. (US 2012/0156251 A1).
Claims 100 and 137-143 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 11,896,677 in view of Brito et al. (US 2012/0156251 A1).
Claims 100 and 137-143 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 12,133,894 in view of Brito et al. (US 2012/0156251 A1).
Claims 100 and 137-143 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 12,433,957 in view of Brito et al. (US 2012/0156251 A1).
The instant claims are drawn to a method of optimizing delivery of a bioactive agent to a cell comprising selecting a particular molar ratio of ingredients. The material being delivered to the cell appears to be a nanostructured lipidic carrier comprising a nucleotide that encodes an antigen. The nanostructured lipidic carrier comprises an oil core with a solid and liquid phase lipid, a cationic component a hydrophobic surfactant, and a second surfactant that may be hydrophilic, as of claim 101.
The conflicting claims in all of the above-indicated cases are drawn to a composition comprising a lipid particle containing a liquid lipid (i.e. liquid oil), a cationic lipid, a hydrophilic surfactant, and a hydrophobic surfactant, or a method of making or using such a composition. These are used to deliver a bioactive agent which is an RNA encoding an antigen.
The conflicting claims do not recite optimization of the amounts of ingredients.
Brito et al. (hereafter referred to as Brito) is drawn to cationic oil in water emulsions used to deliver an RNA molecule encoding an antigen, as of Brito, title and abstract. Brito teaches the following, as of paragraphs 0210-0211, reproduced in the obviousness rejection above. As such, Brito appears to teach optimizing the N/P of a composition comprising particles delivering RNA to optimize expression of said RNA. The N/P ratio refers to the molar ratio of nitrogen in the cationic lipid in the particle to phosphorus in the RNA, as explained by paragraph 0210 of Brito.
It would have been prima facie obvious for one of ordinary skill in the art to have optimized the amounts and/or concentrations of ingredients in the composition of the conflicting claims and the composition used in the method of the conflicting claims. The conflicting claims are drawn to a composition and method for administering a bioactive agent that is RNA that encodes an antigen. The composition of the conflicting claims has essentially the same ingredients as that recited by instant claim 101. The teachings of Brito would have motivated the skilled artisan to have optimized the amounts and concentrations of various ingredients in order to have predictably improved gene expression with a reasonable expectation of success.
The examiner further notes that the conflicting claims in all of the above-listed conflicting patents recite the presence of an inorganic particle; see e.g. claim 21 of patent 12,433,957 as an example. This inorganic particle is not recited by the instant claims. Nevertheless, this is not sufficient to overcome the applied double patenting rejection. This is because, while the instant claims do not recite the inorganic particle, the instant claims also do not exclude an inorganic particle. The transitional term "comprising", which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See MPEP 2111.03(I). Also, while various dependent claims of the conflicting patents recite this inorganic particle, the inorganic particle is not recited by the independent claims of the conflicting patents, resulting in the inorganic particle being an optional ingredient in the conflicting claims. A reference disclosing optional inclusion of a particular component teaches compositions that both do and do not contain that component; see MPEP 2123(I). As such, the presence of dependent claims in the conflicting patents drawn to inorganic particles does not rebut this double patenting rejection.
Claims 100 and 137-153 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 12,485,163 in view of Brito et al. (US 2012/0156251 A1).
The instant claims are drawn to a method of optimizing delivery of a bioactive agent to a cell comprising selecting a particular molar ratio of ingredients. The material being delivered to the cell appears to be a nanostructured lipidic carrier comprising a nucleotide that encodes an antigen. The nanostructured lipidic carrier comprises an oil core with a solid and liquid phase lipid, a cationic component a hydrophobic surfactant, and a second surfactant that may be hydrophilic, as of claim 101.
The conflicting claims are drawn to a composition comprising a lipid particle containing a liquid lipid (i.e. liquid oil), a cationic lipid, a hydrophilic surfactant, and a hydrophobic surfactant, or a method of making or using such a composition. These are used to deliver a bioactive agent which is an RNA encoding an antigen. Conflicting claim 13 recites myristic acid triglycerin, which reads on the required trimyristin and is a solid lipid.
The conflicting claims do not recite optimization of the amounts of ingredients.
Brito et al. (hereafter referred to as Brito) is drawn to cationic oil in water emulsions used to deliver an RNA molecule encoding an antigen, as of Brito, title and abstract. Brito teaches the following, as of paragraphs 0210-0211, reproduced in the obviousness rejection above. As such, Brito appears to teach optimizing the N/P of a composition comprising particles delivering RNA to optimize expression of said RNA. The N/P ratio refers to the molar ratio of nitrogen in the cationic lipid in the particle to phosphorus in the RNA, as explained by paragraph 0210 of Brito.
It would have been prima facie obvious for one of ordinary skill in the art to have optimized the amounts and/or concentrations of ingredients in the composition of the conflicting claims and the composition used in the method of the conflicting claims. The conflicting claims are drawn to a composition and method for administering a bioactive agent that is RNA that encodes an antigen. The composition of the conflicting claims has essentially the same ingredients as that recited by instant claim 101. The teachings of Brito would have motivated the skilled artisan to have optimized the amounts and concentrations of various ingredients in order to have predictably improved gene expression with a reasonable expectation of success.
Note Regarding Declaration from Parent Application
The examiner notes that parent application 17/470,874 includes a declaration under 37 C.F.R. 1.132 in its file record. Affidavits or declarations, such as those submitted under 37 CFR 1.130, 1.131 and 1.132, filed during the prosecution of the prior application (such as application 17/470,874) do not automatically become a part of this application. Where it is desired to rely on an earlier-filed affidavit or declaration, the applicant should make the remarks of record in this application and include a copy of the original affidavit or declaration filed in the prior application.
Conclusion
No claim is allowed.
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ISAAC . SHOMER
Primary Examiner
Art Unit 1612
/ISAAC SHOMER/ Primary Examiner, Art Unit 1612
Prosecution Insights