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 .
Priority
This application is a 371 of PCT/JP2021/037413 filed October 8, 2021 and claims foreign priority to JP 2020-171532 filed October 9, 2020. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been received. The Examiner notes that no English language translation has been provided.
Election/Restrictions
Applicant’s election with traverse of Group I (i.e., claims 1-10 and 17-26 drawn to a population of β(1[Wingdings font/0xE0]3) glucan/nucleic acid complexes in the reply filed on Oct 03, 2025, is acknowledged. The traversal is on the ground(s) that i) no indication was provided that the content of the claims interpreted in light of the description was considered in making the assertion of a lack of unity and therefore has not met the burden necessary to support the assertion; ii) the office action has not considered the relationship of the inventions of Groups I to III with respect to 37 CFR § 1.475(b)(3) and MPEP §806.03; and iii) a search of all the claims would not impose a serious burden on the examiner as per MPEP §803. This is not found persuasive because Applicants are citing requirements for restriction in an application filed under 35 U.S.C. 111(a) incorrectly. The argument is not persuasive because instant application is a 35 U.S.C. 371 filing, not a 35 U.S.C. 111(a) filing. Accordingly, examiner used the requirements for lack of unity as set forth in MPEP §823. As discussed in the election requirement of 8/25/2025, examiner established that the special technical feature of β(1[Wingdings font/0xE0]3) glucan/nucleic acid complexes bound by H-bonds is not a contribution over prior art. is not a consideration in setting forth the lack of unity requirement in a 371 application.
With respect to the remainder of Applicants arguments, i) Examiner has followed the guidance in MPEP §1850 II; and ii) the office action has considered the relationship of the inventions of all Groups I to III with respect to 37 CFR § 1.475(b)(3). 37 CFR § 1.475(c)that follows CFR § 1.475(b)(3) states: If an application contains claims to more or less than one of the combinations of categories of invention set forth in paragraph (b) of this section, unity of invention might not be present. The Groupings indicate that the categories are more than one combination of categories; i.e., Group I: product, Group II: method of making, and Group III: a process of use.
The requirement is still deemed proper and is therefore made FINAL.
Status of Claims
Claims 1-10 and 17-26 are under consideration.
Specification
The use of the term Dawn Heleos-11 in para [0098], which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Applicants help is sought in checking the entire disclosure for any other trade names or marks used in commerce, and appropriately identifying the same.
Claim Rejections - 35 USC § 112
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
Written Description
Claims 1-10 and 17-26 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Independent claims 1, 10, and 18 are drawn to the genus of isolated nucleic acid polymer complexes composed of a homogenous nucleic acid and a hydrogen bonding polymer comprising a multi-stranded beta -1,3-glucan with hydrogen-bonding sites that are made available to interact with the nucleic acid by unbinding the beta-1,3-glucan strands to form a single stranded beta-1,3-glucan that can form a complex with a single stranded nucleic acid to form a population of β(1[Wingdings font/0xE0]3) glucan/nucleic acid complexes wherein the complex forms a triple helix; i.e., a strict molecular ratio exists between the β(1[Wingdings font/0xE0]3) glucan and the homogenous nucleic acid it bonds with (via H-bonding). The nucleic acid must be bonded to the hydrogen-bonding polymer through the hydrogen-bonding sites. The complexes can have any number of nucleic acids as long as at least 30% of the complexes have i) nucleic acids of same length and at least 30% of the complexes have ii) 1, 2, or 3 nucleic acids H-bonded to the β(1[Wingdings font/0xE0]3) glucan. i) and ii) are not necessarily the same population. Claim 10 further requires that ii) is ii-b); i.e., homogenous with respect to the number; i.e, any one of 1, 2, or 3 nucleic acids in the population are H-bonded to the β(1[Wingdings font/0xE0]3) glucan.
Species not described
1. It is noted that although the interaction between the nucleic acid and the beta-1,3-glucan is described in the specification in terms of a single stranded nucleic acid (polyd(A)), the claims are not limited to complexes in which the nucleic acid is single stranded. Instead the claims read on complexes in which the nucleic acid is, e.g., double stranded or triple stranded but specifically a (any) homo-polymer.
2. It is noted that although the beta-1,3-glucan described in the specification is mostly Schizophyllan (SPG), the claims are not limited to complexes in which the nucleic acid is bonded to SPG. Instead the claims read on complexes in which the glucan in the population of β(1[Wingdings font/0xE0]3) glucan/nucleic acid complexes includes the whole genus of β(1[Wingdings font/0xE0]3) glucans, e.g. curdlan. However, curdlan is not known to bind with nucleic acids in a strict molecular ratio via H-bonding, rather an association.
The specification as filed fails to provide an adequate written description of the claimed genera because it does not provide an adequate written description of 1. the nucleic acids that are capable of forming a complex with the recited polymers, and ii) the β(1[Wingdings font/0xE0]3) glucans in the complex, as discussed in more detail below.
Applicant is referred to the Guidelines on Written Description published at FR 66(4) 1099-1111 (January 5, 2001) (also available at www.uspto.gov). The following passage is particularly relevant.
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 structure and function, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
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 a genus, one must describe a sufficient number of species to reflect the variation within the genus. What constitutes a "representative number" is an inverse function of the skill and knowledge in the art. Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that applicant was in possession of the necessary common attributes or features of the elements possessed by the members of the genus in view of the species disclosed. In an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus.
The specification as filed disclosed a limited number of species of nucleic acid that will function in the invention. More specifically, the specification as filed, in the background and specific examples/embodiments shows that complexes can be formed between naturally-occurring schizophyllan and either of poly(dA)or poly(C) ribonucleotides (poly(C): [0003]; poly(A): [0010], [0059] onwards; comparative examples 1-7 and Table 1 - 3, on pages 60 - 72). Further examples demonstrate in vitro activity.
However, the specification does not show:
i) any nucleic acid other than poly(dA) formed a complex
ii) the complex formed between any β(1[Wingdings font/0xE0]3) glucan such as curdlan with a nucleic acid followed any stoichiometric ratio or via H-bonding.
The specification suggests that a complex was formed between schizophyllan and poly(dA), wherein the poly(dA) was in turn bonded to an siRNA (example 8), a double-stranded siRNA (example 9), miRNA (example 10) (pages 72-74). Some of the complexes containing poly(dA) were tested in vitro (examples 9 - 15). No disclosure is provided for a complex comprising a beta-1,3-glucan and the poly(U) double stranded oligonucleotide, or any other homogenous nucleic acid directly, for e.g. Finally, the specification does not indicate the nature of the complex formed between curdlan and either of poly(dA) or any other nucleic acid say poly(dG), as Table 3, where the indication of a complex being formed with curdlan is provided, presents no evidence in this regard.
Such findings regarding poly(A), poly(C) and poly(U) were also presented in Sakurai et al., (J. Am. Chem. Soc. 122: 4520-4521, 4/21/2000, IDS filed April 07, 2023). See e.g., Figs. 2 and 3 on page 4521, and right column. Referring to schizophyllan as “SPG”, and to single chain schizophyllan as “s-SPG”, Sakurai stated that these data “confirm the view that s-SPG/polynucleotide macromolecular complexes are formed at lower temperatures in both poly(dA)+ s-SPG and poly(C) + s-SPG, and no complex is formed in poly(U) + s-SPG. See first full paragraph on page 4521.
Such findings regarding curdlan were also presented in the Gu paper (Lehtovaara et al., Carbohydrate Polymers 87 (2012) 1881– 1885). See e.g. Figs. 1- 2 on pages 1882 and 1883. A gel was formed between curdlan and DNA, with increasing incorporation of DNA into the gel when DNA content was increased. The results do not show that there is a one-to-one ratio of DNA to curdlan interaction. The association with curdlan lacks base pairing type of precision, so it is most likely random rather than strict molecular matching. Gu stated that these data “Using the macroscopic cylinders, the nature of the system as a LCG (Liquid crystalline gels) is verified.”. See first full paragraph on RHS of page 1884.
The instant claims limit the sequence to a homo-polymer comprising any base but the claims do not limit the strandedness of the nucleic acid with which the polymer forms a complex, i.e. the nucleic acid may be of any nucleotide base as long as it is a homo-polymer, and can have any number of strands (double stranded, triple stranded, etc.). The evidence suggests that the nature of the nucleotide bases in the nucleic acid has an effect on whether or not the nucleic acid can form a complex with the beta-1,3-glucan (poly(U) cannot form a complex) and not all β(1[Wingdings font/0xE0]3) glucan bind stoichiometrically with nucleic acids. Moreover, the prior art suggests that schizophyllan does not form a complex with the double stranded RNA oligonucleotide poly(U). However, the claims encompass not just schizophyllan as the glucan to form a complex with either poly(U) or with a poly(A) helix or any other nucleic acid. Neither the specification nor the prior art provides any guidance that would allow one of skill to predict which nucleic acid sequences, other than poly(dA) and poly(C), are suitable to form complexes with naturally-occurring SPG in a strict molecular ratio.
In summary, the claims embrace complexes formed between any beta-1,3-glucans and nucleic acids of any homo-nucleotide sequence or strandedness. The evidence suggests that the art of forming such complexes is unpredictable, and that nucleic acid sequence and strandedness affect whether or not complex formation can be achieved. The specification as filed provides no guidance that would allow one of skill in the art to predict which nucleic acid sequences will support complex formation. The disclosure of a SPG and a homopolymeric oligonucleotide such as poly(dA) that support complex formation does not provide the basis for predicting which of the practically infinite number of nucleic acid species embraced by the claims will have the requisite complex-forming activity. The disclosure of only one species in an unpredictable art would not convey to one of skill that Applicant was in possession of the breadth of the genus that is claimed.
Dependent claims 2-9, 19-26, and 17 are also rejected because they depend on Claim 1 and 10 respectively and do not remedy the issues of lack of written description as discussed above.
Examiner Suggestion: Amend the claims to recite the nucleic acid structures and β(1[Wingdings font/0xE0]3) glucans with hydrogen-bonding sites on the polymer chain that are supported by the evidence to form triple helices in strict stoichiometric ratio by H-bonding.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1 – 10 and 17 – 24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sakurai (Sakurai & Mochizuki, WO 2016/098832, IDS dated April 07, 2023). The human-assisted machine-English translation was relied upon for citation.
Regarding claims 1 – 10 and 17 – 24: Sakurai teaches a polynucleotide/schizophyllan composite that includes schizophyllan (i.e., a β(1[Wingdings font/0xE0]3) glucan) and a polynucleotide or a polynucleotide derivative (that has a CpG sequence) and is hydrogen bonded to the schizophyllan such that the complex comprises one molecular chain of the polynucleotide or the polynucleotide derivative and two molecular chains of the schizophyllan (abstract; English translation, pg. 23, paras. 0073-0074). The phosphate backbones of DNA are phosphorothioate (English translation, pg. 23, para. 0073). An example of a complex is: ((dA) 40-K3) with poly dA tail: (dA) 40, attached to K-type CpG DNA, with schizophyllan (English translation, pg. 23, paras. 0073-0074). Sakurai teaches the difference in molecular weight of the complex can be manipulated in order to isolate the product (English translation, pg. 24, para. 0076). Sakurai teaches that the particle size of the complexes formed depend on the molecular weight of schizophyllan utilized, wherein the radii increase with an increase in molecular weight of schizophyllan (i.e. particle size is manipulated, and thereby controlled, English translation, pg. 25-26, para. 0080, pg. 26, table 6). Although Sakurai does not disclose the particle size or % of the composition complexes above, the particle sizes inherently differ and are thus controlled, allowing any % of the composition to comprise a particular population as required by instant claims, absent evidence to the contrary. Particularly, Sakurai’s description of one molecular chain of the polynucleotide and two molecular chains of the schizophyllan meet instant claims recitation of homo-polynucleotide that binds to β(1[Wingdings font/0xE0]3) glucan via a hydrogen bond contained in one molecule of the complex is 1, 2 or 3 (claims 1 – 10, 17 - 24). With respect to the limitation of nucleic acids in the complex being homogenous in length as specifically recited in claim 10, Sakurai discloses the type and number of bases and nucleotides; i.e., length of nucleic acids in the complex can be controlled depending on the length of the attached polynucleotide or polynucleotide derivative portion having the CpG sequence, the molecular weight of the schizophyllan used, and other factors (English translation, pg. 14, para. 0043).
Thus, Sakurai anticipates instant claims 1 – 10 and 17 – 24.
Claim Rejections - 35 USC § 103
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
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 25 – 26 are rejected under 35 U.S.C. 103 as being unpatentable over Sakurai (Sakurai & Mochizuki, WO 2016/098832, IDS filed September 11, 2023) as applied to claims 1 – 10 and 17 – 24 above. The human-assisted machine-English translation was relied upon for citation.
Regarding claim 25: As discussed above Sakurai teaches the complex of claim 1.
Sakurai does not explicitly teach wherein the nucleic acid in the complex comprises an antisense nucleic acid, siRNA or miRNA as the additional nucleic acid, attached to the 5’ end, as recited by instant claims 25-26.
However, Sakurai teaches that they previously disclosed that schizophyllan forms new types of complexes with various nucleic acids, including nucleic acid drugs such as antisense DNA and further citing various patent and non-patent literature (English translation, pg. 3, para. 0005), as required by claim 25. The further limitations of nucleic acids i.e., siRNA or miRNA is recited as optional, the cited prior art renders obvious the embodiments were siRNA or miRNA are not explicitly required.
Regarding claim 26, Sakurai teaches the complexation of CpG DNA to the 5’ end of the polyd(A) (5 '-(dA) 40-ATCGACTCTCGAGCGTTCTC -3 '(SEQ ID NO: 1; (dA) 40-K3) with poly dA tail: (dA) 40 added as K-type CpG DNA with schizophyllan (English translation, pg. 23, paras. 0073-0074).
Since Sakurai and the references cited by Sakurai are directed to nucleic acid/β-1,3-glucan complexes for transfection, it would have been prima facie obvious to a person of ordinary skill in the art at the time of invention to use antisense nucleic acid, siRNA or miRNA as the additional nucleic acid instead of CpG as the nucleic acid in the complex as taught by Sakurai with the predictable result of creating a complex suitable for transfection. One would be motivated to make such a combination for the advantage of using a natural compound as a carrier for transporting a therapeutic nucleic acid into a cell. Given the teachings of the prior art and the level of the ordinary skilled artisan at the time of the Applicant’s invention, it must be considered, absent evidence to the contrary, that said skilled artisan would have had a reasonable expectation of success in practicing the claimed invention. See MPEP 2143 B.
Thus, Sakurai makes obvious instant claims 25 - 26.
Therefore the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHABANA MEYERING, Ph.D. whose telephone number is (703)756-4603. The examiner can normally be reached M - F: 9am to 5pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ram Shukla can be reached at (571) 272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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SHABANA S. MEYERING, Ph.D.
Examiner
Art Unit 1635
/SHABANA S MEYERING/ Examiner, Art Unit 1635
/RAM R SHUKLA/ Supervisory Patent Examiner, Art Unit 1635