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 Group I (claims 133-150) in the reply filed on February 3, 2026 is acknowledged.
Claims 151-152 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on February 3, 2026.
Applicants also elected the following species, without traverse: siRNA, SEQ ID NO: 22, SEQ ID NO: 1, SEQ ID NO: 19, an antibody, and a circular polynucleotide. However, upon further consideration, the election of species requirement is withdrawn. Claims 133-150 will be examined in their entirety.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, U.S. Provisional Patent Application No. 63/308,776 fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The prior-filed application fails to provide support for any of SEQ ID NOS: 22-26.
Therefore, claims 135 and 145-146 have an effective filing date of February 9, 2023, which is the filing date of the instant application, which is the earliest application to disclose the listed sequences described above. Claims 133-135, 136-143, and 147-150 are deemed to have an effective filing date of February 10, 2022, the filing date of U.S. Provisional Patent Application No. 63/308,776.
Information Disclosure Statement
The Information Disclosure Statements filed August 19, 2024 (4) have been considered.
Specification
The use of the terms TRITON and LIPOFECTAMINE, which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear 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.
Claim Objections
Claims 133 is objected to because of the following informalities:
At claim 133, line 3, “an adaptor molecule” should be changed to “the adaptor molecule.”
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 133-150 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 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 Gostelli, 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.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co., the court stated:
A written description of an invention involving a chemical genus, like a description of a chemical species, "requires a precise definition, such as by structure, formula, [or] chemical name," of the claimed subject matter sufficient to distinguish it from other materials. Fiers v. Revel, 984 F.2d at 1171,25 USPQA2d, 1601; In re Smyth, 480 F.2d 1376,1383, 178 USPQ 279,284 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is an unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus...") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is "not a sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence." MPEP § 2163. The MPEP does state that, for a generic claim, the genus can be adequately described in the disclosure presents a sufficient number of representative species that encompass the genus. MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitutes a sufficient number of representative species, the courts have indicated what does not constitute a representative number of species to adequately describe a broad genus. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872 F.2d at 1012, 10 USPQ2d at 1618. 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: (1) Actual reduction to practice, (2) Disclosure of drawings or structural chemical formulas, (3) Sufficient relevant identifying characteristics (such as: i. Complete structure, ii. Partial Structure, iii. Physical and/or chemical properties, iv. Functional characteristics when coupled with a known or disclosed structure, and v. Correlation between function and structure), (4) Method of making the claimed invention, (5) Level of skill and knowledge in the art, and (6) Predictability in the art.
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. This disclosure of only one or a few species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 115; Noelle v. Lederman, 355 F.3d, 1343, 1350, 69 USPO2d 1508, 1514 (Fed. Cir. 2004) ("[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated."). In addition, it has been well known that minor structural differences even among structurally related compounds can result in substantially different biology, expression, and activities. The instant claims require i) a cargo sequence, which can be an miRNA, an siRNA, an antisense RNA, or a sequence that encodes for an antibody, an enzyme or a protein and ii) a targeting moiety is selected from an antibody, a ligand for a receptor, a vitamin, a hormone, a small molecule mimetic of a ligand, a peptide, a polypeptide, a peptidomimetic, a carbohydrate, a lipid, an aptamer, a nucleic acid, a toxin, a microorganism component, and any molecule that binds to a cell surface molecule and induces endocytosis, and a combination thereof. The rejected claims thus comprise vast genuses of cargo polynucleotides and targeting moieties. The specification recites that cargo polynucleotide can encode any of any siRNAs, miRNAs, antisense RNAs, enzymes, antibodies, or any protein. The specification further recites that the targeting moiety can be any type of molecule, between nucleic acids, peptides, small molecules, as noted above.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof. The specification, while providing sequences and examples of dendrimer binding sequences, DNA targeting sequences, nuclear localization sequences, linker sequences, and support molecule sequences, fails to provide any specific examples of cargo polynucleotides or targeting moieties.
Thus, it is impossible for one to extrapolate from the vast list of cargo polynucleotides and targeting moieties to specific, functioning entities.
The prior art does not appear to offset the deficiencies of the instant specification. The prior art teaches that, while “RNAi is more and more popular for gene targeting and gene silencing,” “to identify efficient and safe vectors do deliver siRNA for successful RNAi process remains the major challenge, both in vitro and in vivo” (Wu et al., 2013 The Scientific World Journal 630654, 1-16 (2013), and cited in the Information Disclosure Statement filed August 19, 2024).
In addition, the prior art discloses dendrimers and their use in pharmaceutical delivery (Mittal et al., 2021 BioMed Research International 8844030, 1-11 (2021), and cited in the Information Disclosure Statement filed August 19, 2024) (abstract). Mittal, while noting that dendrimers’ three dimensional structure can incorporate a wide variety of drugs (abstract). However, while Mittal does note that usefulness of dendrimers, the instant specification itself fails to disclose or suggest any specific cargo polynucleotide or targeting moiety that can be used with the claimed DNA dendrimers.
Thus, the variation in the cargo polynucleotides and targeting moieties are complex and are not extrapolatable to all possible uses of DNA dendrimers.
Therefore, the description of the cargo polynucleotides and targeting moieties is not sufficient to support the genus of cargo polynucleotides and targeting moieties. Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed.” (See Vas-Cath at page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is now is claimed." (See Vas-Cath at page 1116). As discussed above, the skilled artisan cannot envision the detailed cargo polynucleotides and targeting moieties. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential antibody-DNA conjugate. The compound itself is required. See Fiers v. Revel, 25USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18USPQ2d 1016. Therefore, the skilled artisan would have reasonably concluded applicants were not in possession of the claimed invention for claims 133-150.
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 133-150 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.
At claim 133, lines 1-2, it is not clear what is meant by “a DNA dendrimer . . . or associated with a targeting moiety and an adaptor molecule0cargo polynucleotide complex.” Is the association a physical association, a covalent association, or is any proximity of the DNA dendrimer and the targeting moiety/adapter molecule-cargo polynucleotide complex acceptable? If the dendrimer and complex are in proximity with each other, is there a minimum and/or maximum distance between the two components?
Claims 134-150 depend from claim 133, and are therefore included in this rejection.
At claim 135, lines 1-2, it is not clear if the claimed nucleotide sequences must recite the specific sequences. It is suggested that “a” at line 1 be changed to “the.”
At claim 147, improper Markush language is used. In order to provide the required closed group from which the targeting moiety is selected, “or” at line 6 should be changed to “and.”
At claim 148, line 2, it is not clear if the information in the parentheses is intended to be a claim limitation or not. It is suggested that “(e.g., plasmid)” be deleted.
At claim 148, improper Markush language is used. In order to provide the required closed group from which the cargo polynucleotide is selected, “or” at line 4 should be changed to “and.”
Claim 149 depends from claim 148, and is therefore included in these rejections.
At claim 149, line 4, it is not clear if the DTS is the same DTS as claimed in claim 133, or if the DTS of claim 149 is a different DTS.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 133-134, 137-138, 140-144, and 146-150 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 12, 14, 16-17, 19, 21-24, 28-36, 38-39, and 45-47 of copending Application No.19/509,826 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘826 application and the instant application claim DNA dendrimers and compositions comprising the dendrimers.
Regarding claim 133, the ‘826 application claims a composition comprising: a DNA dendrimer; a targeting moiety; and an adaptor molecule-cargo polynucleotide complex, wherein the DNA dendrimer is linked to, conjugated to, or associated with the targeting moiety and the adaptor molecule-cargo polynucleotide complex. The ‘826 application claims the adaptor molecule-cargo polynucleotide complex comprises an adaptor molecule and a cargo polynucleotide. The ‘826 application claims the cargo polynucleotide comprises at least one promoter and at least one coding sequence encoding for at least one molecule of interest. The ‘826 application claims the cargo polynucleotide further comprises at least one DNA targeting sequence (DTS). The ‘826 application claims the cargo polynucleotide further comprises at least one nuclear localization signal sequence (NLS). The ‘826 application claims the adaptor molecule comprises a DNA dendrimer binding sequence (DBS) and a cargo binding region (CBR). The ’826 application claims the cargo polynucleotide encodes for an antibody, an enzyme, a protein, a miRNA, a siRNA, or an antisense RNA (claims 1-2, 5-8).
Regarding claim 134, the ‘826 application claims the adaptor is linked to the DNA dendrimer through the DBS, wherein the DBS comprises a nucleic acid sequence that is complimentary to a nucleic acid sequence on the DNA dendrimer (claim 9).
Regarding claim 137, the ‘826 application claims the adaptor molecule further comprises a tag, a tag that can be used as an affinity tag to isolate/purify the composition complex (claim 11).
Regarding claim 138, the ‘826 application claims the adaptor molecule further comprises at least one NLS, wherein the at least one NLS is located between or overlaps with the DBS and the cargo binding region (claim 12).
Regarding claims 140 and 146, the ‘826 application claims the nitrogen/phosphate (N/P) ratio of the support molecule is between 0.5 and 10 (claims 46).
Regarding claim 141, the ‘826 application claims the at least one NLS further comprises at least one spacer located before or after the at least one NLS, wherein the at least one spacer comprises polyethylene glycol (PEG), propylene glycol alginate (PGA), PEG-polylactic acid (PLA), poly lactic-co-glycolic acid (PGLA), a glycine/alanine spacer, a glycine/serine spacer, or any combination thereof (claim 14).
Regarding claim 142, the ‘826 application claims the adaptor molecule further comprises at least one DTS, wherein the at least one DTS is located between or overlaps with the DBS and the CBR. The ‘826 application claims the adaptor molecule further comprises a cell penetrating peptide sequence (CPP), wherein the CPP is located between or overlapping with the DBS and the CBR (claims 16-17).
Regarding claim 143, the ‘826 application claims the adaptor molecule further comprises at least one cleavage site (claim 19).
Regarding claim 144, the ‘826 application claims the adaptor molecule further comprises at least one flexible linker selected from the group consisting of polyethylene glycol (PEG), 196 propylene glycol alginate (PGA), PEG-polylactic acid (PLA), poly lactic-co-glycolic acid (PGLA), (GG)n, (GGGGS)n, or (GGGGA)n, wherein each n is, independently, 1-5 (claim 21).
Regarding claim 147, the ‘826 application claims the targeting moiety is selected from the group consisting of an antibody, a naturally-occurring ligand for the receptor or a functional derivative thereof, a vitamin, a hormone, a small molecule mimetic of a naturally-occurring ligand, a peptide, a polypeptide, a peptidomimetic, a carbohydrate, a lipid, an aptamer, a nucleic acid, a toxin, a component of a microorganism, any other molecule provided it binds specifically to the cell surface molecule and induces endocytosis of the bound moiety, or any combination thereof (claims 28 and 30).
Regarding claim 148, the ‘826 application the cargo polynucleotide is a nicked circular polynucleotide, a linear polynucleotide with a closed 5' and 3' end, a linear polynucleotide with open 5' and 3' ends, or a linear polynucleotide with one open and one closed end, wherein the one open and one closed end can be at either the 5' and 3' of the polynucleotide (claims 34 and 50).
Regarding claim 149, the ‘826 application claims plasmid backbone comprising at least two enzyme restriction recognition sites, at least one promoter, at least one coding sequence encoding for at least one molecule of interest, and, optionally, a DBS, wherein the plasmid is capable of forming a cargo polynucleotide with various structures depending on whether the plasmid has one or more, or none of, a 5' end and a 3' end (claim 50).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented (claim 47).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Getts et al. (Getts I, U.S. Patent No. 12,076,410, issued September 3, 2024) disclose nucleic acid carriers comprising one or more layers comprising multiple monomers. Getts I discloses that such multi-molecular scaffold devices include DNA dendrimers. However, Getts I fails to disclose or suggest compositions of DNA dendrimers that have the instantly claimed structures and components.
Getts et al. (Getts II, U.S. Patent Application Publication No. 2021/0121580, published April 29, 2021, and cited in the Information Disclosure Statement filed August 19, 2024) disclose DNA dendrimers comprising DNA sequences that encode a polypeptide or a regulatory sequence. Getts II discloses that the regulator sequence can be an siRNA, an miRNA, or an shRNA (see paragraph [0015]). However, Getts II also fails to disclose or suggest compositions of DNA dendrimers that have the instantly claimed structures and components.
Liu et al. (9 Journal of Materials Chemistry B 4991-5007 (2021)) disclose that DNA dendrimer nanostructures have been applied in biosensing, therapeutics, and protein engineering (abstract). Liu discloses a history and timeline of dendrimer applications and research (Table 1 and Figure 2). While Liu also discloses that DNA dendrimers can be used to deliver various agents, including drugs, for the treatment of a variety of diseases (page 5002, column 2, first paragraph) and for gene therapy using antisense oligonucleotides, siRNAs, and DNAzymes (page 5003, column 2, first full paragraph), Liu does not disclose or suggest the DNA dendrimer compositions having the instantly claimed structures and components.
Thus, although DNA dendrimers and uses thereof are known, the prior art fails to disclose or suggest the claimed composition comprising a DNA dendrimer linked to a targeting moiety and an adaptor molecule-cargo polynucleotide complex having the claimed structure of a dendrimer binding sequence, a cargo binding region, a DNA targeting sequence, at least one nuclear localization sequence, at least one promoter, and a cargo sequence.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NANCY J LEITH whose telephone number is (313)446-4874. The examiner can normally be reached Monday - Thursday 8:00 AM - 6:30 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, NEIL HAMMELL can be reached at (571) 270-5919. 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.
NANCY J. LEITH
Primary Examiner
Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636
Prosecution Insights