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 .
Election/Restrictions
Applicant’s election without traverse of the single payload species of CRISPR-Cas-associated complex in the reply filed on August 27, 2025 is acknowledged.
Therefore, the election is made FINAL.
Summary
Claims 27-46 are pending in this office action. Claims 1-26 are cancelled. All pending claims are under examination in this application.
Priority
The current application filed on October 19, 2022.
Information Disclosure Statement
Receipt of the Information Disclosure Statements filed on October 19, 2022 and January 15, 2024 are acknowledged. A signed copy of both documents are attached to this office action.
Claim Objections
Claim 34 is objected to because of the following informality:
Claim 34: The text, “…extension- branching…” has an additional space. Please remove the space.
Appropriate correction is required.
Claim Rejections - 35 USC § 112 – Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 28 is rejected under 35 U.S.C. 112, first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated: "To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Costello, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966." Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include "level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient." MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
In this instance, claim 28 states a claim limitation, “wherein the reaction media has an ionic strength below 1 Mol/L, facilitating long-range electrostatic interactions between the first polymer ion and the second polymer ion prior to their combining.” The specification fails to support a written description for a reaction media having an ionic strength of below 1 Mol/L.
(1) Level of skill and knowledge in the art:
The level of skill and knowledge in the art is replete with regards to providing the nanoencapsulation of an active pharmaceutical compound. "A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR International Co. v. Teleflex Inc., 127 S.Ct. 1727, 167 LEd2d 705, 82 USPQ2d 1385, 1397 (2007). "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle." Id. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ." Id. At 1396, 82 USPQ2d at 1396. 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).
(2) Partial structure:
The specification teaches an example of the nanoencapsulation (see pages 25-28) and briefly discusses ionic strength (“If formulation prepared without a salt (PBS), the TMC-TPP particles will disintegrate as soon as they contact with blood during injection because blood has the same ionic strength as PBS.” See page 8)
However, the specification fails to address (written description) the claim limitation as stated within instant claim 28 [ionic strength <1M].
(3) Physical and/or chemical properties and (4) Functional characteristics:
The physical and/or chemical properties of the composition which provide for the ionic strength of below 1 Mol/L are not discussed within the specification.
At no point within the specification do the inventors discuss this limitation. The definition of ionic strength is not enough to describe to the skilled artisan why a value below 1 Mol/L is needed to facilitate long-range electrostatic interactions between the first polymer ion and the second polymer ion prior to their combining.
(5) Method of making the claimed invention:
A written description requirement generally involves the question of whether the subject matter of a claim is supported by the disclosure of the specification. The subject matter of the claims imply that a reaction media that has an ionic strength below 1 Mol/L, facilitating long-range electrostatic interactions between the first polymer ion and the second polymer ion prior to their combining is an important limitation. However, the specification fails to provide a suitable written description for the property of the ionic strength of the reaction media.
Accordingly, it is deemed that the specification fails to provide adequate written description for the ionic strength of below 1 Mol/L and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Claim Rejections - 35 USC § 103
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.
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 non-obviousness.
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.
Claims 27-46 are rejected under 35 U.S.C. 103 as being unpatentable over
Watson et al. (CA3045134A1) in view of Sung et al. (US2012/0258176A1) Sung et al. ‘200 (US2008/0233200A1), Nilubol et al. (EP3536312A1), Lotfi et al. (Biomedicine & Pharmacotherapy, 2020) and De Boer et al. (WO2021/236952A1, published November 2021).
[The Examiner is going to introduce each new reference and then combine them where appropriate.]
1. Watson et al.
Watson et al. is the closest prior art to the present invention as it teaches compositions and methods for nucleic acid and/or protein payload delivery (see title). Furthermore, Watson et al. disclose that provided are methods and compositions for nanoparticle delivery of payloads (e.g., nucleic acid and/or protein payloads) to cells. In some embodiments, a subject nanoparticle includes a core and a sheddable layer encapsulating the core, where the core includes (i) an anionic polymer composition; (ii) a cationic polymer composition; (iii) a cationic polypeptide composition; and (iv) a nucleic acid and/or protein payload; and where: (a) the anionic polymer composition includes polymers of D-isomers of an anionic amino acid and polymers of L-isomers of an anionic amino acid, and/or (b) the cationic polymer composition comprises polymers of D-isomers of a cationic amino acid and polymers of L-isomers of a cationic amino acid. In some cases, the polymers of D-isomers of an anionic and/or cationic amino acid are present at a ratio, relative to the polymers of L-isomers, in a range of from 10:1 to 1:10. (see abstract).
2. Sung et al.
Sung et al. teach nanoparticles for protein drug delivery (see title). Additionally, Sung et al. disclose particulate complexes composed of chitosan, poly-glutamic acid, and at least one bioactive agent, wherein equal moles of the positively charged chitosan and the negatively charged poly-glutamic acid substrate form an electrostatic network enabling improved loading the bioactive agent. (see abstract).
3. Sung et al. ‘200
Sung et al. ‘200 teach nanoparticles for protein drug delivery (see title). In addition, Sung et al. ‘200 disclose the nanoparticles composed of chitosan, poly-glutamic acid, and at least one bioactive agent characterized with a positive surface charge and their enhanced permeability for paracellular drug delivery (see abstract).
4. Nilubol et al.
Nilubol et al. teach a method for producing acid resistant macrobeads containing nanoparticles and use of the macrobeads for eliciting an immune response (see title). Also, Nilubol et al. disclose that the present invention relates to methods and means for the production of alginate/chitosan acid-resistant macrobeads comprising alginate/chitosan nanoparticles, wherein the nanoparticles comprise a bioactive agent, wherein the bioactive agent is associated via physicochemical interaction with a polymer. The invention further relates to nanoparticles and/or macrobeads obtained by methods of the invention and such nanoparticles and/or macrobeads for use in eliciting an immune response in an animal. Also encompassed by the invention is the use of a porcine epidemic diarrhea virus (PEDV) antigen as defined herein for producing a nanoparticle or acid-resistant macrobeads and a vaccine comprising such an antigen. (see abstract).
5. Lotfi et al.
Lotfi et al. teach CRISPR/Cas13: a potential therapeutic option of COVID-19 (see title). Additionally, Lotfi et al. disclose that the novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be considered as the most important current global issue, as it has caused the novel coronavirus disease (COVID-19) pandemic, which has resulted in high mortality and morbidity rates all around the world. Although scientists are trying to discover novel therapies and develop and evaluate various previous treatments, at the time of writing this paper, there was no definite therapy and vaccine for COVID-19. So, as COVID-19 has called ideas for treatment, controlling, and diagnosis, we discussed the application of Clustered Regularly Interspaced Short Palindromic Repeats/Cas13 (CRISPR/Cas13) as a treatment of COVID-19, which received less attention compared with other potential therapeutic options (see abstract).
6. De Boer et al.
De Boer et al. teach compositions and methods for producing human polyclonal antibodies (see title). Further, De Boer et al. disclose compositions and methods for generating polyclonal antibodies, for example, using circular polyribonucleotides and non-human animals having humanized immune systems. (see abstract).
Combination of Watson et al., Sung et al., Sung et al. ‘200, and Nilubol et al.
Regarding instant claim 27, Watson et al., Sung et al., Sung et al. ‘200, and Nilubol et al. teach a method of nanoencapsulation of an active pharmaceutical compound (payload). The necessary citations within Watson et al., Sung et al., Sung et al. ‘200, and Nilubol et al. that correspond to instant claim 27 are compiled within Table I.
Table I
Instant Claim 27
Watson et al., Sung et al., Sung et al. ‘200, and Nilubol et al. Citation
A method of nanoencapsulation of an active pharmaceutical compound (payload) comprising:
Watson et al. disclose a method of nanoencapsulation of an active pharmaceutical compound, such as a CRISPR-Cas-associated complex, comprising ionizing the payload, combining the ionized payload with a first polymer of opposite charge, then combining with a second polymer of opposite charge to the first polymer to form nanoparticle (see title, abstract, page 2, lines 22-26, and claim 1 within Watson et al.).
Sung et al. disclose a method of nanoencapsulation of an active pharmaceutical compound comprising ionizing the compound, such as negatively charged DNA, combining the ionized compound with a first polymer of opposite charge, such as positively charged chitosan, which is then combined with negatively charged poly-glutamic acid. A wide variety of therapeutic agents are disclosed as being useful in the method, including antineoplastic agents (anticancer agents) and antiviral agents (see title, abstract, claim 21, and paragraphs [0017] and [0022] within Sung et al.).
Sung et al. ‘200 disclose a method of nanoencapsulation of an active pharmaceutical compound comprising ionizing the compound, such as calcitonin, which is positively charged at pH 7.4, combining the ionized compound with a first polymer of opposite charge, such as negatively charged polyglutamic acid, which is then combined with positively charged chitosan. A wide variety of therapeutic agents are disclosed as being useful in the method, including antineoplastic agents (anticancer agents) and antiviral agents (see title, abstract, claim 45, paragraphs [0010] and [0014] within Sung et al. ‘200).
Nilubol et al. disclose a method of nanoencapsulation of an active pharmaceutical compound comprising ionizing the compound, such as negatively charged DNA, combining the ionized compound with a polymer of opposite charge such as a positively charged polymer, then combining with a second polymer, such as a negatively charged polymer. The use of two polysaccharides, such as chitosan (positively charged) and alginate (negatively charged) is also disclosed (see title, abstract, and claim 1 within Nilubol et al.).
a) combining an ionized payload with a first polymer ion of an opposite charge to the ionized payload and a specific size in a low ionic strength reaction media and at a specific concentration resulting in the formation of an initial molecular assembly;
b) combining the initial molecular assembly with an equimolar amount of a second polymer ion of a specific size and of an opposite charge to the first polymer ion such that the ionized payload is trapped between the first and the second polymer ions attached each to the other through opposite charges, while segments of the first polymer ion and/or the second polymer ion remain non-conjugated due to the difference in their sizes, allowing further chain extension and branching;
c) extending and branching the initial molecular assembly by repeated additions of extension-branching polymer ions having alternating charges, specific molecular sizes and stoichiometry corresponding to the number of non-conjugated segments that remain from each previous step, providing a layer-by-layer formation of a particle shell of double-chained conjugated polymer ions; and
A skilled artisan (POSITA; person of ordinary skill in the art) would be able to extend the molecular assembly (disclosed above) by adding polymers with the appropriate charge and size. By choosing the size of the polymer that does not make-up the remaining end portion, the extension can continue until the skilled artisan deems it sufficient. Figure I presented below represents this methodology:
Figure I
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Sung et al. disclose a similar extension but instead use an anionic compound coating (see Example 30 within Sung et al.).
d) end-capping the non-conjugated segments of the first polymer ion or the second polymer ion with end-capping oligomer ions of a complimentary charge to the charge of the last polymer used for extending and branching the initial assembly in step c), resulting in a densely-packed particle with the ionized payload in its center.
After sufficient chain extension the end-capping can be carried out by a skilled artisan (POSITA) upon calculating the size and charge that remains.
The Sung et al. reference within Example 30 also applies for this limitation which “makes the particulate complex more compact.”
It would have been obvious to one of ordinary skill in the art [skilled artisan; POSITA (person of ordinary skill in the art)] prior to the effective filing date of the claimed invention to modify Watson et al. with the teachings of Sung et al., Sung et al. ‘200, and Nilubol et al. to disclose a method of nanoencapsulation of an active pharmaceutical compound (payload) followed by extension of the charged tail to develop a suitable drug delivery vehicle. The motivation for doing so would have been to increase the molecular size to adequately protect the payload from degradation within the biological system.
The combination of Watson et al., Sung et al., Sung et al. ‘200, and Nilubol et al. teach all the elements of instant claim 27 and are therefore applied either directly or indirectly to each independent claim.
Regarding the discussion of instant claim 28, Watson et al., Sung et al., Sung et al. ‘200, and Nilubol et al. teach wherein the reaction media has an ionic strength below 1 Mol/L, facilitating long-range electrostatic interactions between the first polymer ion and the second polymer ion prior to their combining.
Watson et al. disclose a first solution (an anionic solution) was prepared by combining the appropriate amount of payload (in this case plasmid DNA (EGFP-N1 plasmid) with an aqueous mixture (an 'anionic polymer composition') of poly(D-glutamic Acid) and poly(L-glutamic acid). This solution was diluted to the proper volume with 10 mM Tris-HCI at pH 8.5. A second solution (a cationic solution), which was a combination of a 'cationic polymer composition' and a 'cationic polypeptide composition', was prepared by diluting a concentrated solution containing the appropriate amount of condensing agents to the proper volume with 60 mM HEPES at pH 5.5. In this case, the 'cationic polymer composition' was poly(L-arginine) and the 'cationic polypeptide composition' was 16 μg of H3K4(me3) (tail of histone H3, tri methylated on K4) (see Example 2 within Watson et al.). In both examples, where either slightly basic or slightly acidic media is selected the overall ionic strength would be below 1 Mol/L based on the dilute buffer being used in the synthetic procedure.
Regarding the discussion of instant claim 29, Watson et al., Sung et al., Sung et al. ‘200, and Nilubol et al. teach wherein concentration of the ionized payload and of the polymer ions is below 0.5 Mol/L, allowing the polymer ions to take a required shape and orientation prior to their combining.
The Watson et al. procedure from Example 2 further goes onto state, “For the solution of anionic condensing agents, the anionic solutions were chilled on ice with minimal light exposure. 10μg of nucleic acid in aqueous solution (roughly 1 μg/μI) and 7μg of aqueous poly (D-Glutamic Acid) [.1%] were diluted with 10mM Tris-HCI (pH 8.5) to a total volume of 100 μI (as noted above) (see Example 2 within Watson et al.). These amounts suggest values much lower than 0.5 Mol/L.
Regarding the discussion of instant claim 30, Watson et al., Sung et al., Sung et al. ‘200, and Nilubol et al. teach wherein the first polymer ion and the second polymer ion have different linear sizes.
Sung et al. disclose within Example 30 that “[I]n a non-viral carrier for gene delivery, a particle complex (or particulate complex) system comprised of the core CS (chitosan)/DNA complex and the outer coating of an anionic polymer, for example poly(g-glutamic acid) (g-PGA) makes the particulate complex more compact because g-PGA was entangled tightly with the excess CS emanating from the surface of core CS/DNA complexes (also known as test complexes) (see Example 30, paragraph [0238] within Sung et al.). Thus, indicating different polymer chain lengths.
Regarding the discussion of instant claim 31, Watson et al., Sung et al., Sung et al. ‘200, and Nilubol et al. teach wherein the shortest polymer ion has a linear size larger than the ionized payload.
Sung et al. disclose a chitosan size of 30-50kDa (see paragraph [0017] within Sung et al.) and the purified g-PGA has a molecular weight (MW) of about 160 kDa (see paragraph [0093] within Sung et al.). Furthermore, Sung et al. disclose numerous low MW payloads (see paragraph [0022-0023] within Sung et al.).
Regarding the discussion of instant claim 32, Watson et al., Sung et al., Sung et al. ‘200, and Nilubol et al. teach wherein the first and second polymer ions are linear or branched.
Watson et al., Sung et al., Sung et al. ‘200, and Nilubol et al. all support either the use of linear or branched polymeric chains. For example, the shape of the chitosan is dependent on commercial availability.
Regarding the discussion of instant claim 33, Watson et al., Sung et al., Sung et al. ‘200, and Nilubol et al. teach wherein the polymer ions for extending and branching are larger than the charged segments in the molecular assembly, and provides the formation of the same or an increased number of charged segments of reversed polarity within said molecular assembly.
Please see the arguments, discussion, and citations within instant claim 27 for the necessary rejection text. This polymeric extension methodology is non-inventive. A skilled artisan (POSITA) could select polymeric chains of suitable size and charge to extend from the corresponding tails.
Regarding the discussion of instant claim 34, Watson et al., Sung et al., Sung et al. ‘200, and Nilubol et al. teach wherein the first, second and/or extension-branching polymer ions are ionic carbohydrates.
Sung et al. disclose the use of the ionic carbohydrate, chitosan (see paragraph [0017] within Sung et al.).
Regarding the discussion of instant claim 35, Watson et al., Sung et al., Sung et al. ‘200, and Nilubol et al. teach wherein the extension-branching polymer ions are the same as their corresponding first or second polymer ion, or wherein said extension-branching polymer ions are chemically distinct from their corresponding first or second polymer ion.
A skilled artisan (POSITA) could select from the same or different ionic carbohydrates and/or polyamino acids with the appropriate charge for extension purposes.
Regarding the discussion of instant claim 36, Watson et al., Sung et al., Sung et al. ‘200, and Nilubol et al. teach wherein the end-capping oligomer ions are of a broad size distribution.
A skilled artisan (POSITA) could select from a broad range of sizes for the end-capping oligomers.
Regarding the discussion of instant claim 37, Watson et al., Sung et al., Sung et al. ‘200, and Nilubol et al. teach wherein any one or more of the polymer ions or end-capping oligomer ions are chemically combined with at least one biomarker molecule to provide selective cellular uptake of the encapsulated payload.
A skilled artisan (POSITA) could select from wherein any one or more of the polymer ions or end-capping oligomer ions are chemically combined with at least one biomarker molecule to provide selective cellular uptake of the encapsulated payload. The motivation in carrying out this limitation would be to increase the overall selectivity in the treatment regime.
Regarding the discussion of instant claim 38, Watson et al., Sung et al., Sung et al. ‘200, and Nilubol et al. teach wherein the at least one biomarker molecule is a protein, an antibody, or a peptide.
A skilled artisan (POSITA) would use a protein, an antibody, or a peptide as a biomarker to enhance the selectivity.
Regarding the discussion of instant claim 39, Watson et al., Sung et al., Sung et al. ‘200, and Nilubol et al. teach wherein a surface-charge and a polarity of the molecular assembly or particle are controlled by the size and nature of the end-capping oligomer ions.
This claim limitation makes complete sense. The resulting end-cap would dictate the surface charge and polarity (exterior). A skilled artisan (POSITA) would under routine experimental conditions add in components that contribute to the surface charge or polarity depending upon the end-cap group.
Regarding the discussion of instant claims 40, 41, and 45-46, Watson et al., Sung et al., Sung et al. ‘200, and Nilubol et al. teach wherein the payload is a small molecule with acidic or basic groups, an ionizable molecule, a peptide, a protein, a RNA, a DNA, a plasmid, a CRISPR-Cas-associated complex, or any combination thereof.
Sung et al. disclose the nanoparticles are loaded with a therapeutically effective amount of at least one bioactive agent, wherein the bioactive agent is selected from the group consisting of proteins, peptides, nucleosides, nucleotides, antiviral agents, antineoplastic agents, antibiotics, and anti-inflammatory drugs (see paragraphs [0022-0023] within Sung et al.). In addition, Watson et al. disclose nanoparticle formulations including two or more nanoparticles in which the payload of a first nanoparticle includes a donor DNA template and the payload of a second nanoparticle includes a gene editing tool (e.g., (i) a CRISPR/Cas guide RNA; (ii) a DNA encoding a CRISPR/Cas guide RNA; (iii) a DNA and/or RNA encoding a programmable gene editing protein; and/or (iv) a programmable gene editing protein; also see page 33, Gene editing tools) (see page 2, lines 22-26 within Watson et al.). Watson et al. also disclose wherein the target cell is a human cell (see claim 54 within Watson et al.).
Combination of Watson et al., Sung et al., Sung et al. ‘200, Nilubol et al., Lotfi et al., and De Boer et al.
Regarding the discussion of instant claims 42-44, Watson et al., Sung et al., Sung et al. ‘200, Nilubol et al., Lotfi et al., and De Boer et al. teach wherein the payload is a CRISPR-Cas-associated complex comprising a COVID-19 virus or any other virus signature.
Please see the discussion and citations within instant claims 40-41 and 45-46 for the necessary rejection text regarding other virus signatures (generic CRISPR/Cas guide RNA). Watson et al. establishes the use of CRISPR/Cas-associated complexes [CRISPR/Cas9 expression; see Figure 6 (panels A-D) within Watson et al.)]. De Boer et al. disclose tools such as CRISPR/Cas (see page 79, line 2 within De Boer et al.) for use with COVID-19 (see page 95, lines 28-29). Furthermore, Lotfi et al. disclose the use of CRISPR/Cas13 as a potential therapeutic for COVID-19 (see title and abstract within Lotfi et al.). Additionally, two-thirds of viral RNA, principally placed in the 5'-terminal in the first ORF (ORFla/b), translates two polyproteins (PP), ppla and pplb, which codifies 16 non-structural proteins (NSP) (see page 2, left column, paragraph 5 within Lotif et al.) [identified for targeting; nsp12, see 2.1.10; nsp16, see 2.1.14; and nsp14, see 2.1.12 all within Lotif et al.] It would be within the scope of the skilled artisan to target the nsp protein sequence of nsp14A2 from nsp14 disclosed by Lotif et al. (see PTO-892 NPL U).
Analogous Art
The Watson et al., Sung et al., Sung et al. ‘200, Nilubol et al., Lotif et al., and De Boer et al. references are directed to the same field of endeavor as the instant claims, that is, a method of nanoencapsulation of an active pharmaceutical (payload), as disclosed within instant claim 1.
Obviousness Analysis
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of payload delivery for proteins and nucleic acids disclosed by Watson et al., using the teachings of Sung et al., Sung et al. ‘200, Nilubol et al., Lotif et al., and De Boer et al. in order to arrive at the subject matter of the instant claims.
The Watson et al., Sung et al., Sung et al. ‘200, Nilubol et al., Lotif et al., and De Boer et al. references all have considerable overlap in the nanoencapsulation arts for the specific treatment of COVID-19. In this instance, Watson et al., Sung et al., Sung et al. ‘200, and Nilubol et al. supply the methodology for the nanoencapsulation of an active pharmaceutical (payload) including CRISPR/Cas-associated complexes, while Lotif et al. and De Boer et al. supply the COVID-19 specific biology necessary for treatment with the former therapeutic. All references are directed to the nanoencapsulation arts for the specific treatment of COVID-19 and therefore constitute analogous art under MPEP §2141.01(a). A POSITA would have reasonably consulted the six references when seeking to develop an enhanced method for the nanoencapsulation of an active pharmaceutical (payload).
Given these teachings, a POSITA would have been motivated to combine the methodology for the nanoencapsulation of an active pharmaceutical (payload) including CRISPR/Cas-associated complexes as disclosed by Watson et al., Sung et al., Sung et al. ‘200, and Nilubol et al. into the COVID-19 biological data supported by Lotif et al. and De Boer et al. The overarching motivation for doing so would have been to increase the molecular size to adequately protect the payload from degradation within the biological system in order to treat a disease or disorder such as COVID-19.
The modifications constitute a simple substitution of one known element for another to obtain predictable results [MPEP §2143(I)(B)].
The combination represents the use of a known technique to improve a similar device in the same way [MPEP §2143(I)(C)].
The art provides a finite number of identified, predictable solutions, and the POSITA would have pursued the claimed configuration with a reasonable expectation of success [MPEP §2143(I)(E); KSR].
The combination of the methodology for the nanoencapsulation of an active pharmaceutical (payload) including CRISPR/Cas-associated complexes taught by Watson et al., Sung et al., Sung et al. ‘200, and Nilubol et al. along with the use of the COVID-19 biological data supported by Lotif et al. and De Boer et al would allow a research and development scientist (POSITA) to develop the invention taught in the instant application.
Furthermore, the additional claim limitations taught by Lotif et al. and De Boer et al. would have been viewed by a POSITA as routine design optimizations or known modifications for the methodology for the nanoencapsulation of an active pharmaceutical (payload) including CRISPR/Cas-associated complexes. Implementing these features into the nanoparticle of Watson et al., Sung et al., Sung et al. ‘200, and Nilubol et al. would not require more than ordinary skill or routine experimentation.
Accordingly, the combination of Watson et al., Sung et al., Sung et al. ‘200, and Nilubol et al., supplemented by Lotif et al. and De Boer et al. provides all the elements of the claimed invention. The resulting nanoencapsulation of an active pharmaceutical (payload) constitutes no more than the predictable outcome of combining familiar prior art components, and therefore the claimed subject matter would have been obvious to a POSITA prior to the effective filing date of the invention.
Conclusion
No claims are allowed.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert A Wax can be reached on 571-272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC)
at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JOHN W LIPPERT III/Examiner, Art Unit 1615 /Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
Prosecution Insights