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 .
Application Status
Claims 1-2, 8-9, 15-16, 19-22, 28-30, 32, 34, 36-37, and 40-42 are pending.
Response to Election/Restriction
Applicant’s election of Group I (claims 1-2, 8-9, 15-16, 29-30, 37, and 40-42) in the response filed May 30, 2025 is acknowledged. Because Applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Claims 19-22, 28, 32, 34, and 36 are withdrawn from further consideration pursuant to 37 CRR 1.142(b) as being drawn to a non-elected invention. Claims 1-2, 8-9, 15-16, 29-30, 37, and 40-42 are under examination herein.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed provisional application, Application No. 63/277,176 fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Specifically, Application No. 63/277,176 does not disclose the following limitations of instant claims 1 and 29: “said chitosan is 50-100% deacetylated low molecular weight chitosan,” “comprising >50% particles in the range of 10-300 µm,” “2-20 mg/ml low molecular weight chitosan in 0.01-0.1 M organic acid.” The first disclosure of the aforementioned limitations is in Application No. PCT/IL2022/051185, filed November 8, 2022. Because all claims under examination encompass the aforementioned limitations, the effective filing date of all claims under examination is November 8, 2022.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - The incorporation by reference paragraph required by 37 CFR 1.834(c)(1), 1.835(a)(2), or 1.835(b)(2) is missing, defective or incomplete. USPTO records indicate that the title and size of the sequence listing of record, filed August 22, 2024 are “99683.xml” and “154,073 bytes,” respectively, rather than “99683SequenceListing.xml” and “156,914 bytes,” as indicated in the amendments to the specification filed May 9, 2024.
Required response - Applicant must: Provide a substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Drawings
The drawings are objected to because of the following informalities:
The view numbers are preceded by the term “Figure” in the Drawings. 37 C.F.R. 1.84(u)(1) states that “view numbers must be preceded by the abbreviation "FIG."
The lines, shadings, numbers and letters are not sufficient to provide satisfactory reproduction characteristics. 37 CFR 1.84(l) states that “all drawings must be made by a process which will give them satisfactory reproduction characteristics. Every line, number, and letter must be durable, clean, black (except for color drawings), sufficiently dense and dark, and uniformly thick and well-defined.” In the instant case, the Figures contain light colored and/or small text (e.g., Fig. 1, Figs. 7A-B).
Appropriate correction is required.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claims 8-9, 15-16, 29, 37, and 40-42 are objected to because of the following informalities:
Claim 8 recites “about of 30kDa” which should be amended to recite “about
Claim 9 recites “the chitosan:RNA ratio is in the range of 0.45-0.55.” It is clear that the ratio refers to the mass ratio of claim 1. Accordingly, the claim should be amended to recite “the chitosan:RNA mass ratio is in the range of 0.45-0.55.”
Claims 15-16, 29, 37, and 40-42 recite “nutriceutical” which should be amended to recite “nutra[[i]]ceutical.”
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 1-2, 8-9, 15-16, 29-30, 37, and 40-42 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.
Claims 1-2 and 29 recite “low molecular weight chitosan.” “Low” is a relative term which renders the claims indefinite. The molecular weights which are “low” are not defined by the claims. The specification provides many molecular weight ranges for chitosan, e.g., 5-100 kDa, 10-85 kDa, 20-40 kDa, etc. (pg. 13, line 30 to pg. 14, line 4), and indicates that “30,000 daltons” is “very low molecular weight” (pg. 48, lines 2-3). However, the specification does not clearly indicate which molecular weights are considered “low,” such that the skilled artisan could determine which molecular weights are within the scope of the invention.
Claims 2, 15-16, 30, 37, and 40-42 are rejected for depending from claim 1 and failing to remedy the indefiniteness. In the interest of compact prosecution, low molecular weight chitosan will be interpreted as referring to 5-100 kDa (pg. 13, lines 30-31).
Claim 1 recites a “particulate composition comprising chitosan and at least one type of RNA molecule,” which would be interpreted as a mixture of chitosan and an RNA molecule, wherein the mixture is in particle form. The phrase “said particle,” appears to reference the previously recited “particulate composition.” However, the phrase “said particle” is confusing when coupled with the later recited phrase “>50% of particles,” because it is not clear whether the claim is directed to a I) a particle comprising chitosan and an RNA molecule, or II) a composition comprising multiple particles, wherein each particle in the composition comprises chitosan and an RNA molecule.
Claims 2, 8-9, 15-16, 29-30, 37, and 40-42 are rejected for depending from claim 1 and failing to remedy the indefiniteness. In the interest of compact prosecution, the claim is interpreted as being directed to a composition comprising multiple particles, wherein each particle comprises chitosan and an RNA molecule, wherein the mass ratio of each particle is in the range of 0.3-0.9, and wherein >50% of the particles in the composition are in the range of 10-300 µm.
Claim 29 recites “rapidly,” which is a relative term which renders the claim indefinite. The rates which are “rapid” are not defined by the claim, and the specification does not provide a standard for ascertaining the requisite degree of “rapid,” such that the skilled artisan could determine the rates which are within the scope of the invention.
Claim Rejections - 35 USC § 103 – Ufaz in view of Wu and Theerawanitchpan
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.
Claims 1-2, 15-16, 29-30, 37, and 40-42 are rejected under 35 U.S.C. 103 as being unpatentable over Ufaz (Ufaz et al., 13 June 2019, US 2019/0175518 A1; of record), in view of Wu (Wu et al., 26 August 2015, International Journal of Nanomedicine, 2015:10, pg. 5383-5396; of record) and Theerawanitchpan (Theerawanitchpan et al., 2012, Journal of Biotechnology, 160, pg. 97-104; of record).
The phrase “>50% particles in the range of 10-300 µm” is interpreted as referring to the size of particles in the composition, e.g., the size of powder particles following drying and grinding/milling of the chitosan-RNA complex solution (pg. 30, line 28 to pg. 31, line 5; “Chitosan:RNA Particle size distribution”, pg. 52; “dry after milling”, Table V).
Regarding claims 1 and 15, Ufaz teaches particulate chitosan-RNA compositions, wherein the chitosan is deacetylated chitosan, and wherein the RNA comprises a sequence at least 50 bases in length (“Commercially available chitosan is usually provided as a powder… with the degree of deacetylation (% DD) between 60 and 100%, and a molecular weight between about 4 to about 20 kDa”, [0108]; “1.5 g chitosan (HMC+ Chitoscience Chitosan 80/20 Mw 40-150kDa)”, [0268]-[0269]; [0274]-[0275]; “at least one RNA sequence at least 50 bases in length,” claim 1, pg. 34; “nanoparticles were prepared by self-assembly of these chitosans with and 250 bp Rab7 dsRNA” [0289]-[0299]; “Deacetylation degree of chitosan derivatives”, Table 2). Ufaz teaches the chitosan is deacetylated to percentages within the instantly claimed range (Table 2, e.g., “54.9,” “66.2,” “82.4”). Ufaz teaches the RNA is capable of silencing expression of a gene when administered to an organism expressing said gene, e.g., Rab7 in P. vannamei shrimp (“said RNA sequence is capable of silencing expression of a gene when administered to an organism expressing said gene,” claim 1, pg. 34; [0293]-[0294]; Fig. 5).
Ufaz teaches the chitosan is “between about 4 to about 20 kDa,” or “40-150kDa” ([0108]). However, Ufaz does not teach “low molecular weight chitosan,” which is presently interpreted as 5-100 kDa given the indefiniteness described in paragraph 14 above.
MPEP 2144.05(I) states that “In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists.” A range of 5-100kDa overlaps with the ranges disclosed by Ufaz, and thus, a prima facie case of obviousness exists.
Ufaz also teaches a nutraceutical composition comprising farmed crustacean food and the chitosan-RNA particulate composition ([0014]-[0016]; [0211]-[0213]). Ufaz teaches the nutraceutical composition is prepared by mixing with farmed crustacean food ([0219]). Ufaz teaches dried powder formulations of the chitosan-RNA nanoparticles, e.g., spray-dried powders, are suitable for mixing with the farmed crustacean food ([0219]; [0435]-[0436]). Ufaz teaches the compositions are used to treat diseases or conditions in farmed crustaceans, and provide a solution for effective delivery of RNA for commercial farms ([0009]-[0016]; Example VII). However, Ufaz does not teach a particulate composition with particle sizes in the claimed range.
Wu teaches preparation of a spray-dried chitosan-dsRNA powder with particles 5-15 µm in diameter (“Preparation of nanoparticle-loaded spray-dried powders”, pg. 5384; “Characterization of powders”, pg. 5386-5387). Wu teaches that upon reconstitution, the chitosan-dsRNA nanoparticles contained therein are approximately 190 nm in diameter (pg. 5387).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used the spray-drying method of Wu, to prepare the particulate composition of Ufaz, such that the particle sizes are within the instantly claimed size range. It would have amounted to applying a known technique, to a known composition, by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in preparing the particulate composition of Ufaz with Wu’s spray drying technique because Ufaz teaches that spray-dried powder forms of the particulate composition are suitable. Because Ufaz teaches that spray-dried powder forms of the particulate composition can be mixed into farmed crustacean feed to prepare nutraceutical compositions, a skilled artisan seeking to efficiently deliver RNA in aquaculture for the purposes of gene knockdown would have been motivated to apply the technique of Wu to the composition of Ufaz.
Regarding the chitosan:RNA mass ratio (w/w) of the particulate composition, Ufaz teaches that as the degree of chitosan deacetylation is decreased, more chitosan is required to completely bind the same amount of RNA ([0290]). Ufaz teaches that “more deacetylated chitosan binds the dsRNA more efficiently (e.g., complete binding of the dsRNA at a lower polymer/dsRNA mass ratio)” ([0290]). However, Ufaz does not teach a chitosan:RNA mass ratio (w/w) in the claimed range, i.e., at a “lower polymer/dsRNA mass ratio.”
Theerawanitchpan also teaches particulate chitosan-RNA compositions for use in farmed crustaceans, wherein the chitosan:RNA mass ratio (w/w) of the particles is in the within the range of 0.3-0.9, e.g., “0.5:1” or 0.5, “0.7:1” or 0.7, “0.9:1,” or 0.9 (Fig. 1, “Chitosan-dsRNA and QCH4-dsRNA complexes at various weight ratios”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have prepared the particulate composition of Ufaz, with a mass ratio in the range of 0.3-0.9 taught by Theerawanitchpan. It would have amounted to preparing a known composition, at a known mass ratio, by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in preparing the particulate composition of Ufaz at a mass ratio in the range of 0.3-0.9 because Theerawanitchpan teaches substantially identical particulate compositions to Ufaz with mass ratios in this range, for the same purposes taught by Ufaz. The skilled artisan would have been motivated to prepare the particulate composition at one of the lower chitosan-RNA mass ratios taught by Theerawanitchpan because Ufaz teaches that “complete binding of the dsRNA” can be achieved at lower polymer/dsRNA mass ratios.
In view of the above, the particulate composition of claim 1, and the nutraceutical composition of claim 15 are obvious over Ufaz, Wu, and Theerawanitchpan.
Regarding claim 2, Ufaz teaches deacetylated chitosan within the instantly claimed range (Table 2, “82.4”).
Regarding claim 16, Ufaz teaches that the RNA content of the composition is about “10-10,000”, “50-8,000,” “100-5,000,” “200-1,000,” “250-5,000” or “500-5,000” “µg ss or dsRNA per gram of shrimp and/or prawn feed” ([0220]). Expressed in percentages, these ranges are 0.001%-1.0%, 0.005%-0.8%, 0.01%-0.5%, 0.02%-0.1%, 0.025%-0.5%, and 0.05%-0.5% respectively. MPEP 2144.05(I) states that “In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists.” The instantly claimed range of “0.1-3.0%” overlaps with the ranges disclosed by Ufaz, and thus, a prima facie case of obviousness exists.
Regarding claim 29, the claim is directed to the nutraceutical composition of claim 15, wherein the composition is prepared by the recited process. The claim is a product-by-process, the patentability of which is based on the product itself. As described in paragraphs 19-22 above, Ufaz, Wu, and Theerawanitchpan render obvious the nutraceutical composition of claim 15, which comprises a chitosan-RNA complex, wherein the chitosan meets the parameters of claim 1, and therefore, of claim 29 (i.e., “50-100% deacetylated low molecule weight chitosan solution”).
The process steps “adding an RNA solution to… 20-20 mg/ml low molecular weight chitosan in 0.01-0.1 M citric acid,” “desalting and concentrating the chitosan-RNA complex solution,” and “drying the desalted, concentrated chitosan-RNA complex solution,” were also considered to determine whether they would be expected to impart any distinctive structural characteristics to the claimed product. It is not apparent that the concentration of chitosan in an acid solution, or the desalting or drying steps add any distinctive structural characteristics to the claimed product. These general steps appear in the prior art (see Ufaz, [0180]-[0181]; [0269]; [0298]; [0379]). The use of citric acid, specifically, also does not appear to provide any distinctive structural characteristics to the claimed product. The specification asserts that compared to acetic acid (such as that used by Ufaz, [0180]), “[l]actic and citric acids have a better effect on gene silencing… [and] had a superior effect on survival rates according to the viral challenge test (Table VII)” (pg. 53). The results in Fig. 3 and Table VII do not appear to support that preparation with citric acid imparts distinctive structural characteristics to the claimed product; the silencing is similar amongst particles prepared with different acids, and the meaning and relevance of “%RPS” in Table VII is not evident based on the specification. The specification speculates that citric acid may “contribut[e] to dsRNA stabilization,” but does not provide any evidence that it imparts such a structural effect on the claimed product.
Taken together, it is not apparent that the process steps confer any distinctive structural characteristics to the claimed product, and the product appears to be the same or similar to that rendered obvious above. See MPEP 2113(I)-(II).
Regarding claim 30, Ufaz teaches a farmed crustacean comprising the particulate composition (“farmed crustacean comprising the nutraceutical compositions or nanoparticles described herein,” [0247]; “farmed crustacean comprising the nanoparticle,” claim 14, pg. 34).
Regarding claims 37 and 40, Ufaz teaches the at least one type of RNA molecule comprises “at least one sequence capable of binding through complementary base pairing to a target mRNA molecule of a virus pathogenic in farmed crustaceans,” wherein the RNA molecule comprises “a nucleic acid sequence complementary toa nucleic acid sequence selected from the group consisting of SEQ ID NO: 1, 2, 3, and 5” (claims 21 and 40, pg. 34-35). Ufaz’s SEQ ID NOs: 1-3, and 5 are identical to instant SEQ ID NOs: 1-3, and 5. See attached alignments. For the record, it is noted that claim 40 only appears to limit options (a) and (c) of claim 37.
Regarding claim 41, Ufaz teaches the at least one type of RNA molecule comprises “at least one sequence having at least 90% sequence identity to a target mRNA molecule of a virus pathogenic in farmed crustaceans,” wherein the RNA molecule comprises “a nucleic acid sequence identical to at least 21 contiguous bases of a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 59, 64, 77, 78, and 79 (claims 21 and 41, pg. 34-35). Ufaz’s SEQ ID NOs: 59, 64, and 77-79 are identical to instant SEQ ID NOs: 59, 64, and 77-79. See attached alignments. For the record, it is noted that claim 41 only appears to limit options (b) and (d) of claim 37.
Regarding claim 42, Ufaz teaches the particulate composition comprises “at least one additional RNA sequence capable of directing cleavage of a target mRNA molecule of a virus pathogenic in farmed crustaceans” (claim 47, pg. 35)
Claim Rejections - 35 USC § 103 – Ufaz, Wu, and Theerawanitchpan in view of Techaarpornkul and MedChemExpress
Claims 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Ufaz (Ufaz et al., 13 June 2019, US 2019/0175518 A1; of record), Wu (Wu et al., 26 August 2015, International Journal of Nanomedicine, 2015:10, pg. 5383-5396; of record) and Theerawanitchpan (Theerawanitchpan et al., 2012, Journal of Biotechnology, 160, pg. 97-104; of record) as applied to claims 1-2, 15-16, 29-30, 37, and 40-42, in further view of Techaarpornkul (Techaarpornkul et al., 2010, AAPS PharmSciTech, Vol. 11, No. 1, March 2010, pg. 64-72) and MedChemExpress (MedChemExpress, available 22 September 2020, https://www.medchemexpress.com/chitosan-mw-30000.html, record retrieved 30 June 2025 from the WayBack Machine).
The teachings of Ufaz, Wu, and Theerawanitchpan are described above in paragraphs 19-29 and applied hereinafter. As stated above, Ufaz teaches chitosan “between about 4 to about 20 kDa,” or “40-150kDa” ([0108]).
None of Ufaz, Wu, or Theerawanitchpan teach preparing the particulate composition with chitosan of about 30kDa, i.e., 27-33kDa at +/- 10% (pg. 43, line 10; claim 8), or in the range of 20-30kDa (claim 9).
However, Techaarpornkul teaches chitosan-RNA particulate compositions, wherein the percent chitosan deacetylation is similar to that of Ufaz (i.e., “85%,” pg. 65), the mass ratio of chitosan:RNA is similar to that of Wu (i.e., “0.25, 0.5, 1”), and wherein the molecular weight of chitosan is 20kDa or 45kDa (Fig. 2). Techaarpornkul teaches that compared to higher molecular weight chitosan (i.e., 200 or 460kDa), compositions with lower molecular weight chitosan (i.e., 20 and 45kDa) showed much greater gene silencing efficiency in vitro (Fig. 6; pg. 69). The skilled artisan would recognize that Techaarpornkul’s gene silencing effects occur at both 20kDa and 45kDa, and therefore, would have reasonably predicted enhanced gene silencing effects relative to higher molecular weight chitosan between 20-45kDa. As evidenced by Techaarpornkul and MedChemExpress, chitosan was commercially available in molecular weights within this range.
Regarding claim 8, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have prepared the particulate composition rendered obvious above over Ufaz, Wu, and Theerawanitchpan with chitosan of about 30kDa (i.e., 27-33 kDa). It would have amounted to preparing an obvious chitosan:RNA particulate composition, with chitosan of a molecular weight predicted to be effective for gene silencing, by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in preparing the particulate composition, because Techaarpornkul’s composition and the composition rendered obvious above have similar features (i.e., percent deacetylation, mass ratio), and chitosan of about 30kDa is commercially available as evidenced by the prior art. The skilled artisan would have had a reasonable expectation of success in using the particulate composition for its intended purpose because Techaarpornkul demonstrates that compositions comprising lower molecular weight chitosan are effective for gene silencing. The skilled artisan would have been motivated to prepare the particulate composition with chitosan of about 30kDa because Techaarpornkul demonstrates that lower molecular weight chitosan (i.e., 20kDa, 45kDa) is more effective at silencing than higher molecular weight chitosan, and the skilled artisan would reasonably predict that these effects would be present at molecular weights between 20-45kDa.
Regarding claim 9, Theerawanitchpan teaches mass ratios (w/w) within the claimed range, e.g., “0.5:1” or 0.5 (Fig. 1, “Chitosan-dsRNA and QCH4-dsRNA complexes at various weight ratios”). The obviousness of preparing the particulate composition of Ufaz with a mass ratio of Theerawanitchpan is recited in paragraph 22 above and applied herein with respect to claim 9. Regarding the molecular weight of chitosan in the range of 20-30 kDa, the obviousness of preparing the particulate composition with 20-30kDa chitosan is described immediately above and applied herein with respect to claim 9.
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.
U.S. Patent No. 10,973,774
Claims 1-2, 15-16, 29-30, 37, and 40-42 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 10,973,774 in view of Ufaz (Ufaz et al., 13 June 2019, US 2019/0175518 A1; of record), Wu (Wu et al., 26 August 2015, International Journal of Nanomedicine, 2015:10, pg. 5383-5396; of record) and Theerawanitchpan (Theerawanitchpan et al., 2012, Journal of Biotechnology, 160, pg. 97-104; of record).
Patented claim 1 recites “A chitosan-RNA nanoparticle comprising partially deacetylated chitosan and at least one RNA sequence at least 50 bases in length, wherein the degree of deacetylation of said chitosan is in the range of 42% to 35%, and wherein said RNA sequence is capable of silencing expression of a gene when administered to an organism expressing said gene.”
The claims of the ‘774 patent are directed to a nanoparticle comprising deacetylated chitosan and an RNA molecule meeting each limitation of the RNA molecule of instant claim 1. Relative to features of the particle recited in instant claim 1, the claims of the ‘774 patent do not recite that the chitosan is 50-100% deacetylated low molecular weight chitosan (interpreted as 5-100 kDa given the indefiniteness described in paragraph 14 above), that the mass ratio of the chitosan:RNA particle is in the range of 0.3-0.9, or a composition comprising the nanoparticles, in which >50% particles are in the range of 10-300 µm.
The teachings of Ufaz, Wu, and Theerawanitchpan are described in paragraphs 17-29 above and applied hereinafter. As described therein, the limitations of instant claim 1 and its dependents are taught in or obvious over the prior art.
Regarding the molecular weight of chitosan recited in instant claim 1, Ufaz teaches a substantially identical nanoparticle to that of the patented claims, in which the chitosan is “between about 4 to about 20 kDa,” or “40-150kDa” ([0108]). MPEP 2144.05(I) states that “In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists.” A range of 5-100kDa overlaps with the ranges disclosed by prior art, and thus, a prima facie case of obviousness exists with respect to the molecular weight of the instant claims.
Regarding the percent deacetylation recited in instant claims 1-2, the chitosan in Ufaz’s substantially identical nanoparticle is deacetylated to percentages within the instantly claimed range (Table 2, e.g., “54.9,” “66.2,” “82.4”). Ufaz teaches means to prepare nanoparticles with percent deacetylation within the instantly claimed ranges, and demonstrates that the nanoparticles with percent deacetylation in the claimed range are effective for their intended purpose ([0289]-[0290]; Fig. 3; Fig. 5, “H55”).
It would have been obvious to one of ordinary skill in the art before the effective filing date to have modified the percent deacetylation of the patented nanoparticle, to a percent deacetylation taught by Ufaz which lies within the ranges recited in the instant claims. It would have amounted to modifying the percent deacetylation of a patented nanoparticle, by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in preparing the patented nanoparticle with a percent deacetylation in the instantly claimed range based on the teachings of Ufaz. The skilled artisan would have also predicted that the nanoparticle would have been effective for its intended use based on the teachings of Ufaz. Because Ufaz teaches that “more deacetylated chitosan binds the dsRNA more efficiently (i.e., complete binding of the dsRNA at a lower polymer/dsRNA mass ratio), the skilled artisan would have been motivated to prepare the patented nanoparticle with deacetylated chitosan in the percentages instantly claimed, which are higher than that of the patented claims ([0290]).
Regarding the particle size recited in instant claim 1, the obviousness of preparing a spray-dried composition comprising the patented nanoparticles, in which >50% particles are in the range of 10-300 µm as taught by Wu is described in paragraph 21 above and applied herein.
Regarding the chitosan:RNA mass ratio recited in instant claims 1 and 9, the obviousness of preparing the patented nanoparticle with a chitosan:RNA mass ratio within the claimed range of 0.3-0.9, or 0.45-0.55 as taught by Theerawanitchpan is described in paragraph 22 and applied herein.
Patented claim 6 meets the limitations of instant claims 15 and 29, wherein claim 29 is interpreted as a product-by-process claim.
Patented claim 7 meets the limitations of instant claim 30.
Regarding instant claim 16, the patented claims are silent as to the percent RNA content of the nutraceutical composition. However, Ufaz teaches that the RNA content of the composition is about “10-10,000”, “50-8,000,” “100-5,000,” “200-1,000,” “250-5,000” or “500-5,000” µg ss or dsRNA per gram of shrimp and/or prawn feed” ([0220]). Expressed in percentages, these ranges are 0.001%-1.0%, 0.005%-0.8%, 0.01%-0.5%, 0.02%-0.1%, 0.025%-0.5%, and 0.05%-0.5% respectively. The instantly claimed range of “0.1-3.0%” overlaps with the ranges disclosed by the prior art. MPEP 2144.05(I) states that “In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists.” Thus, instant claim 16 is also obvious over the patented claims in view of the prior art.
Patented claims 9, and 16-17 meet the limitations of instant claims 37, and 40-42.
Claims 8-9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 10,973,774 in view of Ufaz (Ufaz et al., 13 June 2019, US 2019/0175518 A1; of record), Wu (Wu et al., 26 August 2015, International Journal of Nanomedicine, 2015:10, pg. 5383-5396; of record) and Theerawanitchpan (Theerawanitchpan et al., 2012, Journal of Biotechnology, 160, pg. 97-104; of record) as applied to claims 1-2, 15-16, 29-30, 37, and 40-42, in further view of Techaarpornkul (Techaarpornkul et al., 2010, AAPS PharmSciTech, Vol. 11, No. 1, March 2010, pg. 64-72) and MedChemExpress (MedChemExpress, available 22 September 2020, https://www.medchemexpress.com/chitosan-mw-30000.html, record retrieved 30 June 2025 from the WayBack Machine).
The claims of the ‘774 patent do not recite a particulate composition with chitosan of about 30kDa, i.e., 27-33kDa at +/- 10% (pg. 43, line 10; instant claim 8), or in the range of 20-30kDa (instant claim 9).
The teachings of Techaarpornkul and MedChemExpress are described above in paragraphs 30-35 and applied hereinafter.
Regarding instant claim 8, the obviousness of preparing the patented particulate composition with chitosan of about 30kDa is described above in paragraph 34 and applied hereinafter.
Regarding instant claim 9, the obviousness of preparing the patented particulate composition with a chitosan:RNA mass ratio in the range of 0.45-0.55 is described above in paragraph 43 and applied hereinafter. The obviousness of preparing the patented particulate composition with chitosan in the range of 20-30kDa is described above in paragraph 34 and applied hereinafter.
Conclusion
No claims are allowed.
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/JENNA L PERSONS/Examiner, Art Unit 1637
/Soren Harward/Primary Examiner, TC 1600