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 .
Status of the Claims
Claims 1-6 are pending and examined on the merits.
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. The instant application claims domestic benefit from U.S. provisional application 63/311717 filed on February 18, 2022.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Objections to the Specification
The disclosure is objected to because of the following informalities:
Claim 1 recites “BMS1” “BMS27” and “PI3K-IN-20” as members of the Markush group of the plurality of drug molecules, however, there appear to be inconsistencies between the drug molecules as claimed and the drug molecules as recited in other parts of the disclosure. “BMS1” is claimed in claim 1 and is singularly recited in the specification at Pg. 2, line 17. However, all further recitations appear as “BMS001” or “BMS 001” (Pg. 2, lines 22, 26, and 30; Pg. 6, line 5; Pg. 7, line 5; and FIGS. 23 and 34). “BMS27” is claimed and recited in the specification at Pg. 2, lines 18, 22, 25, and 30; whereas “BMS37” is recited at Pg. 6, line 11 and Pg. 7, line 11 in the specification as well as in FIGS. 18, 25, and 36. “PI3K-IN-20” is claimed and singularly recited in the specification at Pg. 2, line 18; whereas “PI3K-IN-10” is recited at Pg. 2, lines 22, 26, and 31; Pg. 6, line 20; and Pg. 7, line 20 and in FIGS. 18, 28, 39, and 46. It is unclear whether these are typographical errors relating to the same compound, and, if they are typographical errors, which recitation is the correct name of the compound that is intended to be instantly claimed.
Additionally, FIG. 40 shows a therapeutic structure comprising a DCL ligand and DCL drug combination which is not disclosed elsewhere in the specification or claims. Similarly, FIG. 47 shows UAMC-1110 ligand and UAMC-1110 drug combinations which is not disclosed elsewhere in the specification or claims.
Appropriate correction is required. It appears that some of these inconsistencies may be typographical errors which are intended to refer to the same drug molecule. However, these inconsistencies reduce clarity as to the intended scope of Applicant’s claimed invention. It is recommended that Applicant thoroughly review the full contents of the disclosure for possible typographical errors and make necessary amendments for clarity.
The use of the term GIVLAARI on Pg. 1, line 20 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.
Claim Rejections - 35 USC § 112
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 1-6 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.
Claim 1 recites the term “a RNA nanostructure motion element” in line 2 which renders the claim indefinite. The term “RNA nanostructure motion element”, and specifically the term “motion element” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. As claimed, it is unclear what specific structural and/or functional elements are meant to be encompassed by an “RNA nanostructure motion element”.
Claim 1 recites the term “UAMC-1110 ligand” in line 4 which renders the claim indefinite. It is unclear whether the term ligand is intended to be used as a descriptor for the UAMC-1110 molecule or to refer to an element to which UAMC-1110 binds. Additionally, it is unclear whether the term ligand is intended to distribute to the other members of the Markush group in lines 3 and 4 of claim 1 (i.e., methotrexate (MTX) and N-[N- [(S)-1,3-dicarboxypropyl]carbamoyl]-(S)-lysine (DCL)). Upon review of the prior art, it appears that UAMC-1110 is a ligand for fibroblast activation protein and thus the term ligand is interpreted as intended to be a descriptor of UAMC-1110. The remainder of the action presumes that the term ligand is intended to be used as a descriptor, which appears to be supported by it’s use in the instant specification as it relates to the function of MTX as a ligand for dihydrofolate reductase (Pg. 12, lines 15-16).
Claim 2 recites the limitation "the RNA nanostructure" in line 11. There is insufficient antecedent basis for this limitation in the claim as there is no prior recitation of an RNA nanostructure.
Claims 3-6, which depend from claim 2 are included in this rejection for importing the defect by dependency while not being corrective.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Guo et al. (WO 2019156726 A1, hereafter “Guo”).
The instant application uses the recitation “RNA nanostructure motion element” in line 2 of claim 1. This term is not specifically defined in the instant disclosure. Based on the specification, the term “motion element” appears to refer to “self-motion elements” which enable delivery of a drug to a target (Pg. 2, lines 5-6 and 8-9). However, the term “motion element” does not appear to confer any structural differences to an RNA nanostructure as instantly claimed and therefore is not considered to be limiting. The recitation “RNA nanostructure motion element” appears to refer to a nanoparticle structure comprising RNA oligonucleotides (Specification Pg. 3, lines 8-9; FIG. 2) which are capable of being modified by attachment of additional compounds. This interpretation is used for the purposes of examination.
With regard to claim 1, Guo teaches RNA nanostructures which can be composed of one or more modules or motifs and which can be used in formulations comprising conjugated therapeutic drug cargo, which is considered to read on a therapeutic structure containing RNA nanostructures (Abstract). Guo teaches that the RNA motifs can be composed of at least three synthetic RNA oligonucleotides coupled to each other (Pg. 1, lines 30-31) and which can further include a “cargo compound” (Pg. 2, 1st Para., line 9) and a “functional group” (Pg. 2, 1st Para., line 12), this is considered to reasonably read on an “RNA nanostructure motion element” based on the claim interpretation above. Guo teaches wherein the cargo compound refers to “any molecule, compound, or composition that can be loaded onto the RNA nanostructure…and can be delivered to a subject” (Pg. 36, lines 27-29), which is considered to read on a plurality of drug molecules. Guo also teaches wherein the functional group refers to compounds which add functionality to the RNA nanostructure (Pg. 36, lines 31-33), can comprise a targeting moiety used to direct the RNA nanostructure to a “location, cell type, organ, or structure within a subject” (Pg. 41, lines 25-28), and which can be a compound, molecule, or any other composition (Pg. 41, lines 26-27). Additionally, Guo teaches that the drug molecules and/or functional group can be chemotherapeutics (Pg. 37, line 9) such as paclitaxel (Pg. 40, line 24), camptothecin (Pg. 40, line 25), and methotrexate (Pg. 40, line 33).
As mentioned above under 112 claim rejections, it is unclear if the recitation of “ligand” in line 4 of claim 1 is intended to be interpreted as applying to the entire Markush group as recited in claim 1, lines 3-4 or only to a UAMC-1110 ligand. Guo is silent as to methotrexate’s ability to function as a ligand. However, it is well known in the art that methotrexate functions as a ligand for dihydrofolate reductase which is supported by the instant specification (Pg. 12, lines 15-16).
With regard to claims 2 and 3, Guo teaches RNA nanostructures comprising one or more modules or motifs (Abstract) wherein the RNA motifs can be composed of at least three synthetic RNA oligonucleotides which can be coupled to each other, form a central core domain, and comprise at least three double-stranded arms arranged around the core domain and extending away from the central core domain (Pg. 1, last para and Pg. 2, first para., lines 1-2). Guo teaches wherein the functional group, which may include methotrexate (Pg. 40, line 33), can be attached to a nucleotide of at least one of the synthetic RNA oligonucleotides (Pg. 2, 1st para., lines 12-13) and wherein at least 3 to 100 drug molecules can be attached to a synthetic RNA oligonucleotide (Pg. 2, 1st para., lines 10-11). Guo further teaches wherein the RNA oligonucleotides can be configured to self-assemble to form the RNA motif (Pg. 2, 1st para., lines 18-19), which is considered to read on the RNA nanostructure.
With regard to claim 4, Guo teaches that the functional group, which may include methotrexate (Pg. 40, line 33) can be attached to a terminal nucleotide (Pg. 2, 1st para., lines 13-14).
With regard to claim 5, Guo teaches wherein the RNA nanostructures provide various sites wherein drug molecules can be attached (Pg. 34, lines 10-11) allowing for a plurality of drug molecules to be attached at one or more nucleotides in the double-stranded arms (Pg. 32, lines 25-26 and FIGs. 18 and 20), which is considered to reasonably read on drug molecules which are attached to non-terminal nucleotides.
With regard to claim 6, Guo teaches wherein the Tm of the RNA nanostructure can range from about 65 to 100 degrees Celsius (Pg. 2, 1st para., lines 22-23).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERIN V PAULUS whose telephone number is (571)272-6301. The examiner can normally be reached Mon-Fri 8 AM-5 PM.
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/ERIN V PAULUS/Examiner, Art Unit 1631
/JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631