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 .
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," 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 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) 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") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) 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 of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Specific deficiency - Sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.831(c). Sequence identifiers for sequences (i.e., “SEQ ID NO:X” or the like) must appear either in the drawings or in the Brief Description of the Drawings. Figures 1 and 4 contain sequences that are not accompanied with sequences identifiers (i.e., “SEQ ID NO:X).
Required response – Applicant must provide:
Amended drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers (i.e., “SEQ ID NO:X” or the like) into the Brief Description of the Drawings, 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.
Claim Interpretation
Claims 3, 4, and 5 were interpreted as product-by-process claims. "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) See MPEP 2113.
"The Patent Office bears a lesser burden of proof in making out a case of prima facie obviousness for product-by-process claims because of their peculiar nature" than when a product is claimed in the conventional fashion. In re Fessmann, 489 F.2d 742, 744, 180 USPQ 324, 326 (CCPA 1974). Once the examiner provides a rationale tending to show that the claimed product appears to be the same or similar to that of the prior art, although produced by a different process, the burden shifts to applicant to come forward with evidence establishing an nonobvious difference between the claimed product and the prior art product. In re Marosi, 710 F.2d 799, 803, 218 USPQ 289, 292-33 (Fed. Cir. 1983).
"[T]he lack of physical description in a product-by-process claim makes determination of the patentability of the claim more difficult, since in spite of the fact that the claim may recite only process limitations, it is the patentability of the product claimed and not of the recited process steps which must be established. We are therefore of the opinion that when the prior art discloses a product which reasonably appears to be either identical with or only slightly different than a product claimed in a product-by-process claim, a rejection based alternatively on either section 102 or section 103 of the statute is eminently fair and acceptable. As a practical matter, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons therewith." In re Brown, 459 F.2d 531, 535, 173 USPQ 685, 688 (CCPA 1972).
Here, claims 3, 4, and 5 are drawn to a MERS-CoV vaccine, and not a method of producing the same. As such, for purposes of applying prior art, claims 3, 4, and 5 were broadly interpreted herein encompass any MERS-CoV vaccine having all the recited structural limitations of the MERS-CoV vaccine of claim 1.
Claim Rejections - 35 USC § 112 – 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 1 – 19 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.
Regarding claims 1 and 8, the use of the transitional phrase “having at least 90 % identity over an entire length of the nucleic acid sequence from a spike (S) gene of a MERS-CoV strain” is unclear as to whether open or closed claim language is intended. Claim 8 limits the S gene to SEQ ID NO: 1. The nucleic acid may be defined by the exact SEQ ID NO: 1 or may be comprised of SEQ ID NO: 1. See MPEP 2111.03 (IV). For purposes of compact prosecution and examination, “having” is interpreted as “comprising”.
Claims 8 and 11 recite “The method of claim 1”. Claim 1 is drawn to a composition which is a different statutory category. For purposes of compact prosecution and examination, “The method of claim 1” is interpreted as “The MERS-CoV vaccine of claim 1”.
The dependent claims do not add additional clarity and, therefore, are also indefinite.
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.
Claims 1 - 19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), 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 or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus. See, e.g., Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010); University of California v. Eli Lilly & Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) at 1406; Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021) ("[T]he written description must lead a person of ordinary skill in the art to understand that the inventor possessed the entire scope of the claimed invention. Ariad, 598 F.3d at 1353–54 ('[T]he purpose of the written description requirement is to ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor's contribution to the field of art as described in the patent specification.' (internal quotation marks omitted).").
A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). The issue is whether the skilled artisan would understand inventor to have invented, and been in possession of, the invention as claimed.
The Federal Circuit has clarified the application of the written description requirement to inventions in the field of biotechnology. See University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568,43 USPQ2d l398, 1406 (Fed. Cir. 1997). The Court stated that a written description of an invention requires a precise definition, one that defines the structural features of the chemical genus that distinguishes it from other chemical structures. A definition by function does not suffice to define the genus because it is only an indication of what the genus does, rather than what it is. Further, the Court held that to adequately describe a claimed genus, an applicant must describe a representative number of species of the claimed genus, and that one of skill in the art should be able to “visualize or recognize the identity of the members of the genus.”
The claims are broadly drawn to a genus comprising: a nucleic acid sequence that is at least 90% identical to an entire length of the nucleic acid sequence from a spike (S) gene of a MERS-CoV strain and in claim 8, at least 90% identical to SEQ ID NO: 1. However, the Specification has failed to sufficiently describe the structural features that must be retained by members of the claimed genus as to establish a structure-function relationship with respect to protein function. There is not sufficient description of the structural features that must be retained to establish a functional relationship with respect to humoral stimulation.
The broadest reasonable interpretation of the claims encompasses innumerable permeations of the proteins of the MERS-CoV S protein and, in claim 8, SEQ ID NO:1. The Specification fails to disclose which regions the MERS-CoV S protein and, in claim 8, SEQ ID NO:1 can be mutated, deleted, truncated, etc., or which regions of the MERS-CoV S protein and, in claim 8, SEQ ID NO:1 must be retained with respect to function. The claims improperly define the genus based on what it does—not what it is.
SEQ ID NO: 1 encodes a MERS-CoV spike protein. SEQ ID NO: 1 is 4059 nucleic acids in length. A variant sharing 90% identity to SEQ ID NO: 1 can have anywhere from 1 to 405 substitutions, deletions or additions in any combination along any length of the sequence. Thus, just for substitutions with canonical nucleic acids alone, the instant claims encompass an enormous genus (4405 = 6.8 x 10243) comprising trillions upon trillions of sequences. Furthermore, claim 1 does not define a MERS-CoV S protein sequences, merely reciting 90% of any strain will work. In a rapidly mutating RNA virus, this encompasses innumerable number of strains resulting in an innumerable number of sequences.
While the claims are drawn to a nebulous genus of ill-defined variants, the Specification and Drawings have only adequately described and successfully reduced to practice a singular nucleic acid encoding a MERS-CoV S protein (Figure 1).
Furthermore, the Specification does not adequately describe a method of identifying functional homologs based on sequence homology and, therefore, does not sufficiently meet the written description requirement.
Moreover, Pallesen et al (PNAS, 2017, 10.1073/pnas.1707304114, hereinafter, “Pallesen”) teaches that even single point mutations have drastic effects on antigenicity. Pallesen teaches the introduction of single point mutations on the MERS-CoV S protein (Figure S1). Pallesen teaches that while some mutations can increase antigenicity, other mutations, such as deletions, can drastically reduce antigenicity (Section: Immunogenicity of MERS S-2P, Figure 3).
Similarly, Al-Amri et al (Scientific reports, 2017, 10.1038/srep44875, hereinafter, “Al-Amri”) teaches the immunogenicity of MERS-CoV spike protein DNA vaccines (Abstract). Al-Amri teaches that truncations that result in at least 90% of the full spike protein sequence result in large differences in eliciting an immune response (Figure 1, Figure 2, Figure 4). Al-Amri teaches that while some truncated spike proteins induced an immunogenic response, the humoral response is dependent on the location of the truncation (Figure 4). Thus, when taken with the teachings of Pallesen and Al-Amri, one of skill in the art would readily appreciate that sequence homology alone cannot serve as the basis to describe members of the genus that have the recited function.
In the absence of a representative number of examples, the Specification must at least
describe the structural features that are required for the claimed function, in this case, with regards to a nucleic acid sequence encoding a S protein of a MERS-CoV strain or SEQ ID NO: 1, humoral stimulation.
However, as discussed above, the Specification fails to describe any substantive structural limitations as to establish a structure-function relationship with respect to function, let alone the various improved properties required throughout the instant claims. Applicant merely offers a cursory statement that any nucleic acid sequence with 90% identity to an entire length of the nucleic acid sequence from a S gene of a MERS-CoV strain or SEQ ID NO: 1 will work.
Accordingly, the claims as currently written are not adequately described and one of skill in the art would readily appreciate that Applicant was not in possession of the claimed genus before the effective filing date of the claimed invention.
Claim Rejections - 35 USC § 112 – Scope of Enablement
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 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for inducing an immune response to a MERS-CoV infection within a subject, does not reasonably provide enablement for preventing a MERS-CoV infection. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.” These factors include, but are not limited to:
• (A) The breadth of the claims;
• (B) The nature of the invention;
• (C) The state of the prior art;
• (D) The level of one of ordinary skill;
• (E) The level of predictability in the art;
• (F) The amount of direction provided by the inventor;
• (G) The existence of working examples; and
• (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
Here, the instant claims are broadly drawn to a method for preventing a MERS-CoV infection by administering a nucleic acid encoding MERS-CoV spike protein encapsulated in a nanoparticle. In regard for prevention of MERS-CoV infection, it is noted that the term “preventing” was interpreted in an absolute sense to mean to always keep something from happening or arising. The claims are not enabled based on that not all MERS-CoV infection are prevented by the vaccine being claimed.
The level of skill in the art is high and would include, e.g., Ph.D. level scientists.
The art establishes vaccines similar to those of the instant application are not 100% effecting in preventing MERS-CoV infection as evidenced by Ciaramella et al. (US20200282046A1, hereinafter, “Ciaramella”, Figure 19 A-C). Ciaramella evidences that a nucleic acid encoding MERS-CoV spike protein encapsulated in a nanoparticle has some effect on lessening MERS-CoV infection but that this effect is not 100% successful at preventing a MERS-CoV infection (Figure 19 A-C). Therefore, there is a reasonable expectation that a nucleic acid encoding MERS-CoV spike protein encapsulated in a nanoparticle that would not prevent an infection in all cases.
In view of the evidence discussed above, the vaccine of claim 1 would not predictably prevent infections caused by MERS-CoV in every single case.
The specification only exemplifies and reduces to practice increasing antibody titers towards a MERS-CoV (Figure 10 - 11). Figure 10 depicts the humoral immune response in vaccinated mice groups against MERS-CoV S.FL measured by indirect ELISA at weeks 0, 2, 4, and 6 while figure 11 depicts the binding antibodies responses in vaccinated groups elicited against MERS-CoV S1 and S.FL measured by indirect ELISA at week 6. One of ordinary skill in the art would be unable to determine how the use of a nucleic acid encoding MERS-CoV spike protein encapsulated in a nanoparticle as described in the instant invention would be able to prevent all MERS-CoV infections without extensive further testing, especially in regard to the measurement of symptoms and viral load. Together, the specification offers no reasonable direction or working example for the use of a nucleic acid encoding MERS-CoV spike protein encapsulated in a nanoparticle that prevent all MERS-CoV infections.
In view of the foregoing, a vast quantity of experimentation, including expansive clinical trials, would be needed to use the invention based on the content of the disclosure.
Taken together, the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1 - 5, 7, 8, 10, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al (ACS Appl. Mater. Interfaces, 2020, 10.1021/acsami.0c09484, hereinafter, “Lee”) and in view of Kamegawa et al (Phys. Chem. Chem. Phys., 2013, 10.1039/c3cp51022k, hereinafter, “Kamegawa”), Ciaramella et al (US20200282046A1, hereinafter, “Ciaramella”).
Lee teaches the synthesis of an antigen delivery system comprising of a hollow mesoporous silica nanoparticle (Abstract). Lee teaches the core is composed of iron oxide particles while the shell is silica based (Abstract). Lee teaches large mesopores allow a high loading efficiency (Abstract). Lee teaches the use of 3- aminopropyltrimethoxysilane to modify the surface of the nanoparticle (Section: Surface Modification of H-XL-MSNs ¶1). Lee also teaches the use of the nano particle loaded with an antigen for immunotherapy (Abstract).
Regarding claims 1 and 2, Lee teaches a silica base nanoparticles that are functionalized with 3 - aminopropyltrimethoxysilane (Section: Surface Modification of H-XL-MSNs ¶1).
Lee teaches the nanoparticle is comprised of a iron-oxide and silica that is functionalized with 3 – aminopropyltrimethoxysilane. Lee does not teach a base nanoparticle functionalized with 3 – aminopropyltrimethoxysilane is that is comprised of aluminosilicate base.
However, Kamegawa teaches an aluminosilicate mesoporous nanoparticle with hierarchical architecture (Abstract). Kamegawa teaches by using a solvent evaporation and poly(methyl methacrylate) (PMMA), the pore size of the nanoparticle can become macroporous (Abstract).
Regarding claim 1, Kamegawa teaches an aluminosilicate mesoporous nanoparticle with hierarchical architecture (Abstract).
Both Lee and Kamegawa do not teach the encapsulation of a nucleic acid that is related to the MERS-CoV S gene within the nanoparticle.
However, regarding claim 1, Ciaramella teaches RNA vaccines comprising a lipid nanoparticle and a nucleic acid encoding a Betacoronavirus S protein (Abstract, Claim 1). Ciaramella teaches that the S protein can be a MERS-CoV S protein (¶0047).
As discussed above, claims 3, 4, and 5 are product-by-process claims that have been interpreted as a MERS-CoV vaccine having all the recited structural limitations of the MERS-CoV vaccine of claim 1. = Ciaramella teaches a nucleic acid sequence encoding a MERS CoV S protein (Ciaramella sequence 68). Ciaramella teaches the nucleic acid can be DNA or RNA (¶0022-0023, sequence 68).
Regarding claim 7, Ciaramella teaches a nucleic acid encoding a MERS CoV S protein that is 4071 nucleotide long (Ciaramella sequence 68).
Regarding claim 8, Ciaramella teaches a nucleic acid sequence encoding a MERS CoV S protein that has 92% sequence identity to SEQ ID NO: 1 (nucleic acids 19 - 617 reproduced below, Query is SEQ ID NO:1, Sbjct is Ciaramella).
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Regarding claim 10, sequence 68 of Ciaramella has a GC content of 59.86% (4071 bases, 1064 G, 1373 C).
Regarding claim 19, Ciaramella teaches the intramuscular injection of a composition comprising a lipid nanoparticle and a nucleic acid encoding a MERS-CoV S protein to induce an immune response (¶0096 – 0097).
Lee, Kamegawa, and Ciaramella are considered to be analogous to the claim invention because they describe nanoparticles. Lee teaches silica nanoparticles functionalized with 3- aminopropyltrimethoxysilane to encapsulate antigens (Abstract). Kamegawa teaches a hierarchical mesoporous aluminosilicate nanoparticle (Abstract). Ciaramella teaches the encapsulation of mRNA encoding a MERS-CoV S protein within a nanoparticle (Claim 1).
Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to have functionalized an aluminosilicate base nanoparticle using 3- aminopropyltrimethoxysilane, as taught by Lee and Kamegawa, to encapsulate a MERS-CoV antigen because doing so would eliminate the need for an aluminum-based adjuvant when stimulating an immune response towards MERS-CoV. One of ordinary skill in the art would have had a reasonable expectation of success in functionalizing an aluminosilicate base nanoparticle using 3- aminopropyltrimethoxysilane encoding a MERS-CoV S antigen given that encapsulating antigens in inorganic nanoparticles is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Claim(s) 6 is rejected under 35 U.S.C. 103 as being unpatentable over Lee, Kamegawa, and Ciaramella as applied to claims 1 - 5, 7, 8, 10, and 19 above, and further in view of Al-Eid et al(Catalysis Research, 2022, 10.21926/cr.2204035, hereinafter, “Al-Eid”) and Meng et al (Journal of Industrial and Engineering Chemistry, 2016, 10.1016/j.jiec.2016.02.012, hereinafter, “Meng”).
As discussed above, claims 1 - 5, 7, 8, 10, and 19 were rendered prima facie obvious by Lee, Kamegawa, and Ciaramella. While the references teach an aluminosilicate nanoparticle functionalized with 3- aminopropyltrimethoxysilane that encapsulates a MERS-CoV S nucleic acid, the references fail to teach a molar ratio of silicon dioxide to aluminum oxide in the aluminosilicate is from 70:1 to 90:1.
However, Al-Eid teaches the preparation of different ZSM-5 compositions (Abstract). Al-Eid teaches ZSM-5-based composition can have differing pore sizes and three-dimensional interconnected channel system (Introduction ¶2, Table 1). Al-Eid also teaches that ZSM-5 can be composed of different silicon dioxide to aluminum oxide ratios (Section 2.1: Raw Materials).
Meng teaches the use of aluminosilicate composites synthesized using chitosan (Abstract). Meng teaches this composite can be used for drug delivery (Abstract). Meng teaches that different silicon dioxide to aluminum oxide ratios affect pore size among other properties of the nanoparticle (Abstract).
Regarding claim 6, Al-Eid teaches ZSM-5 zeolites can have a silicon dioxide to aluminum oxide ratio of 80:1 (Section 2.1: Raw Materials). Meng teaches that increasing the silicondioxide to aluminum oxide ratio increased pore size (Figure 2, Results and discussion ¶1, 2). It would have been a matter of routine experimentation using standard laboratory techniques available at the time of filing to determine the optimal silicon dioxide to aluminum oxide ratio of the starting material for use and modification in the method taught by Lee, Kamegawa, and Ciaramella to control pore size with a reasonable expectation of success. As taught by Meng, one of ordinary skill in the art would be motivated to optimize the silicon dioxide to aluminum oxide ratio to control the pore size of the nanoparticle. “[W]here 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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Here, the instant claims encompass routing concentration ranges for protein digestion which evidences that a particular concentration is not critical and readily obtained by routine optimization.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Claim(s) 11 is rejected under 35 U.S.C. 103 as being unpatentable over Lee, Kamegawa, and Ciaramella as applied to claims 1 - 5, 7, 8, 10, and 19 above, and further in view of Hudson et al (US20190262472A1, hereinafter, “Hudson”).
As discussed above, claims 1 - 5, 7, 8, 10, and 19 were rendered prima facie obvious by Lee, Kamegawa, and Ciaramella. While the references teach an aluminosilicate nanoparticle functionalized with 3- aminopropyltrimethoxysilane that encapsulates a MERS-CoV S nucleic acid, the references fail to teach an average pore size distribution of 8 to 9 nm.
However, regarding claim 11, Hudson teaches the preparation of compositions of drug nanoparticles (Abstract). Hudson teaches that the surface of the nanoparticle can be a mesoporous silicate and can be functionalized with 3-aminopropyltrimethoxysilane (¶0033). Hudson teaches the silicate can be an aluminosilicate (¶0034). Hudson teaches polyproteins such as enzymes enter the pores of the MPS and that the pore size can be 20nm or less (¶0033).
It would have been a matter of routine experimentation using standard laboratory techniques available at the time of filing to determine the optimal pore size for the encapsulation of nucleic acids in the method taught by Hudson, in the functionalized aluminosilicate taught by Lee, Kamegawa, and Ciaramella, to control pore size with a reasonable expectation of success. As taught by Hudson, the ideal pore size depends on the cargo being delivered. Hudson teaches the identification of an ideal pore size for proteins and therefore, one of ordinary skill would be motivated to optimize the pore size ideal for the delivery of nucleic acids. “[W]here 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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Here, the instant claims encompass routing concentration ranges for protein digestion which evidences that a particular concentration is not critical and readily obtained by routine optimization.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Claim(s) 12 is rejected under 35 U.S.C. 103 as being unpatentable over Lee, Kamegawa, and Ciaramella as applied to claims 1 - 5, 7, 8, 10, and 19 above, and further in view of Huiyong et al (Microporous and Mesoporous Materials, 2009, 10.1016/j.micromeso.2008.09.020., hereinafter, “Huiyong”) andVallet-Regi et al (Chem Soc Rev, 2022, 10.1039/d1cs00659b, hereinafter, “Vallet-Regi”).
As discussed above, claims 1 - 5, 7, 8, 10, and 19 were rendered prima facie obvious by Lee, Kamegawa, and Ciaramella. While the references teach an aluminosilicate nanoparticle functionalized with 3- aminopropyltrimethoxysilane that encapsulates a MERS-CoV S nucleic acid, the references fail to teach an aminopropyltrimethoxysilane functionalized aluminosilicate has a BET surface area of 120 m2/g to 160 m2/g.
However, regarding claim 12, Huiyong teaches the synthesis of ZSM-5-MCM-41 micro-mesoporous composites by a two-step crystallization process based on the polymerization of ZSM-5 nanocluster precursors confined to the MCM-41 structure-directing agent using microwave radiation crystallization technology (Abstract). Huiyong also teaches the characterization of ZSM-5, MCM-41, and ZSM-5-MCM-41 by calculating the accessible solvent surface area, total pore volume, small-angle and wide-angle X-ray diffraction patterns, and toluene adsorption (Abstract). Huiyong teaches a surface area of 100 - 200 m2/g (Section 4.1. Structural details ¶3).
It would have been a matter of routine experimentation using standard laboratory techniques available at the time of filing to determine the optimal surface area for the encapsulation of nucleic acids in the method taught by Huiyong, in the functionalized aluminosilicate taught by Lee, Kamegawa, and Ciaramella, to control pore size with a reasonable expectation of success. Vallet-Regi teaches that total surface area of a nanoparticle affects the pore volume and pore size and the amount of functionalization of the nanoparticle (Introduction ¶1, Section: 2. Mesoporous materials for drug delivery ¶3, Figure 8). As evidenced by Vallet-Regi, one of ordinary skill in the art would be motivated to optimize the surface area of the nanoparticle to attenuate functionalization of the nanoparticle and to optimize cargo adsorption (Introduction ¶1, Figure 8). “[W]here 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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Here, the instant claims encompass routing concentration ranges for protein digestion which evidences that a particular concentration is not critical and readily obtained by routine optimization.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Claim(s) 13 is rejected under 35 U.S.C. 103 as being unpatentable over Lee, Kamegawa, and Ciaramella as applied to claims 1 - 5, 7, 8, 10, and 19 above, and further in view of Seo et al (US20190382273A1, hereinafter, “Seo”) and Vallet-Regi.
As discussed above, claims 1 - 5, 7, 8, 10, and 19 were rendered prima facie obvious by Lee, Kamegawa, and Ciaramella. While the references teach an aluminosilicate nanoparticle functionalized with 3- aminopropyltrimethoxysilane that encapsulates a MERS-CoV S nucleic acid, the references fail to teach an aminopropyltrimethoxysilane functionalized aluminosilicate has a BJH surface area of 80 m2/g to 90 m2/g.
However, Seo teaches nanostructured aluminosilicates including nanorods that are formed by heating a geopolymer resin (Abstract). Seo teaches characteristics of the aluminosilicates after different methods of treatment (Abstract, ¶0015). Seo teaches that by changing starting parameters such as water content, pH, and temperature, the characteristics of the aluminosilicates change (¶0015-0018).
Regarding claim 13, Seo teaches the BJH calculated surface area of aluminosilicates can be between 50 m2/g and 400 m2/g (Abstract, ¶0012, Example 1).
It would have been a matter of routine experimentation using standard laboratory techniques available at the time of filing to determine the optimal surface area for the encapsulation of nucleic acids in the method taught by Seo, in the functionalized aluminosilicate taught by Lee, Kamegawa, and Ciaramella, to control pore size with a reasonable expectation of success. As taught by Vallet-Regi, one of ordinary skill in the art would be motivated to optimize the surface area of the nanoparticle to attenuate functionalization of the nanoparticle and to optimize cargo adsorption (Introduction ¶1, Figure 8).“[W]here 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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Here, the instant claims encompass routing concentration ranges for protein digestion which evidences that a particular concentration is not critical and readily obtained by routine optimization.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Claim(s) 14 is rejected under 35 U.S.C. 103 as being unpatentable over Lee, Kamegawa, and Ciaramella as applied to claims 1 - 5, 7, 8, 10, and 19 above, and further in view of Kang et al (Desalination and Water treatment, 2016, 10.1080/19443994.2015.1014856, hereinafter, “Kang”).
As discussed above, claims 1 - 5, 7, 8, 10, and 19 were rendered prima facie obvious by Lee, Kamegawa, and Ciaramella. While the references teach an aluminosilicate nanoparticle functionalized with 3- aminopropyltrimethoxysilane that encapsulates a MERS-CoV S nucleic acid, the references fail to teach an aminopropyltrimethoxysilane functionalized aluminosilicate has a pore volume of 0.2 to 0.4 cm3/g.
However, regarding claim 14, Kang teaches the synthesis and functionalization of the mesoporous aluminosilicate MCM-41 with 3- aminopropyltrimethoxysilane (Abstract). Kang teaches the characterization of the functionalized MCM-41 (f-MCM-41) using field emission electron microscopy, energy-dispersive X-ray spectrometry, transmission electron microscopy, particle size analysis, nitrogen gas adsorption-desorption analysis, X-ray diffraction spectrometry, and infrared spectrometry (Abstract). Kang teaches a total pore volume of 0.342 cm3/g (Section 3.1. Characteristics of MCM-41 and f-MCM-41 ¶1, Table 1).
Lee, Kamegawa, Ciaramella, and Kang are considered to be analogous to the claim invention because they describe nanoparticles. It would have been prima facie obvious before the effective filing date of the claimed invention to have functionalized an aluminosilicate base such as MCM-41, as taught by Kang, nanoparticle using 3- aminopropyltrimethoxysilane, as taught by Lee and Kamegawa, to encapsulate a MERS-CoV antigen because doing so would eliminate the need for an aluminum-based adjuvant when stimulating an immune response towards MERS-CoV. One of ordinary skill in the art would have had a reasonable expectation of success in functionalized an aluminosilicate base nanoparticle using 3-aminopropyltrimethoxysilane encoding a MERS-CoV S antigen given that encapsulating antigens in inorganic nanoparticles is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Claim(s) 9 and 15 -18 are rejected under 35 U.S.C. 103 as being unpatentable over Lee, Kamegawa, and Ciaramella as applied to claims 1 - 5, 7, 8, 10, and 19 above, and further in view of Cha et al (Molecules, 2017, 10.3390/molecules22050782, hereinafter, “Cha”).
As discussed above, claims 1 - 5, 7, 8, 10, and 19 were rendered prima facie obvious by Lee, Kamegawa, and Ciaramella. While the references teach an aluminosilicate nanoparticle functionalized with 3- aminopropyltrimethoxysilane that encapsulates a MERS-CoV S nucleic acid, the references fail to teach an aminopropyltrimethoxysilane functionalized aluminosilicate has a pore volume of 0.2 to 0.4 cm3/g.
However, Cha teaches the use of DNA, miRNA, siRNA, and antisense oligonucleotides encapsulated in mesoporous silica nanoparticles for therapeutic treatments (Abstract). Cha teaches the nanoparticles function to deliver and protect the nucleic acids (Abstract). Cha teaches strategies for the preparation of nanoparticles encapsulating nucleic acids as well as a summary of recent applications of the encapsulated nanoparticles (Abstract).
Regarding claim 9, Cha teaches a weight ratio of the silicate nanoparticles to nucleic acid at 100:1.5 (Section: 3.2. MiRNA/siRNA-MSN Complexes for miRNA/siRNA Delivery and miRNA/siRNA-Guided Therapeutics ¶3). Cha also teaches “the nucleic acid/MSN ratio of the complexes was usually optimized and determined through evaluation of their complexing and delivery efficiency of nucleic acids by MSNs” (Section 2. General Strategies for Preparation of Nucleic Acid-MSN Complexes ¶1).
Regarding claim 15 - 18, Cha teaches that functionalization of the surface of silica nanoparticles affects the encapsulation efficiency of pDNA and RNA (Section 2. General Strategies for Preparation of Nucleic Acid-MSN Complexes ¶1). Cha also teaches pore structure affects the encapsulation efficiency of nucleic acids (Section 2. General Strategies for Preparation of Nucleic Acid-MSN Complexes ¶1).
It would have been a matter of routine experimentation using standard laboratory techniques available at the time of filing to determine the weight ratio, encapsulation efficiency, and total amount of nucleic acids in the functionalized aluminosilicate taught by Lee, Kamegawa, and Ciaramella, to deliver nucleic acids with a reasonable expectation of success. As taught by Cha, one of ordinary skill in the art would optimize the nucleic acid to nanoparticle ratio to modulate complexing and delivery efficiency of the payload. “[W]here 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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Here, the instant claims encompass routing concentration ranges for protein digestion which evidences that a particular concentration is not critical and readily obtained by routine optimization.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Conclusion
NO CLAIMS ARE ALLOWED
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/DANYAL HASSAN ALAM/Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672
