DETAILED ACTION
Notice of 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 .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Election/Restrictions
Applicant’s election without traverse of Group I and the following species in the reply filed on 03/31/2026 is acknowledged:
Applicant elected the process/method: claims 48-61;
Applicant elected the method comprising staple crossover asymmetry of claims 2-4 (i.e. claims 5-8 are nonelected);
Applicant elected the input step of claim 9 (i.e. claims 10-12, 14-16 and 21 are nonelected);
Applicant elected the square as the morphology of claim 11;
Applicant elected the identifying step of claims 22-23 (i.e. claim 24-25 are nonelected);
Applicant elected the kind of helices spanning each edge of claims 35-38 (i.e. claims 34-47 from Groups II-VII are nonelected);
Applicant elected the two anti-parallel helices spanning each edge as the kind of helices spanning each edge of claim 35) (i.e. claims 34-47 from Groups II-VII are nonelected);
Applicant elected the RNA scaffold comprising one or more selected from the group consisting of mRNA, repRNA, genomic transcript RNA of claims 48-54, 60; and
Applicant elected the antisense molecules, siRNA, miRNA, shRNA, RNAi as the kind of functional RNA of claim 54.
In this instant application, claims 5-8, 10-12, 14-16, 21, 24-25 and 34-47 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention/species there being no allowable generic or linking claim. Claims 1-4, 9, 13, 17-20, 22-23, 26-33 and 48-61 are being examined on the merits.
Status of the Claims
Claims 1-61 are pending.
Claims 5-8, 10-12, 14-16, 21, 24-25 and 34-47 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species/invention, as set forth in the Restriction Requirement dated 01/08/2026.
Claims 1-4, 9, 13, 17-20, 22-23, 26-33 and 48-61 are examined.
Claims 1, 3, 22, 49-50 and 52-53 are objected to.
Claims 1-4, 9, 13, 17-20, 22-23, 26-33 and 48-61 are rejected.
Priority
This US Application 18/191,723 (03/28/2023) claims benefit of US Application 63/324,538 (03/28/2022), as reflected in the filing receipt mailed on 06/12/2023. The claims to the benefit of priority are acknowledged; and the effective filing date of claims 1-4, 9, 13, 17-23, 26-33 and 48-61 is 03/28/2022.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 11/07/2023 was considered by the examiner.
Claim objections
Claim 1 is objected to because of the following informality: the recited step (b) is missing punctuation at the end of line 2.
Claim 1 is objected to because of the following informality: missing a conjunction -"and/or" - between steps (b)(ii) and (b)(iii).
Claim 3 is objected to because of the following informality: the recited "of from" presents improper writing structure.
Claim 22 is objected to because of the following informality: the recited "wherein" clause of step (iii) presents incorrect indentation. As set forth in 37 CPR 1.75, each element or step of the claim should be separated by a line indentation (608.01(m) Form of Claims). Sub-steps / elements should be indented from their parent step / element. This rule should be applied throughout the claims as needed.
Claims 49-50 and 52-53 are objected to because of the following informality: the previously introduced abbreviation " messenger RNA (mRNA)" has not been used properly. There is no need to repeat the word "messenger RNA" once the abbreviation has been introduced in claim 48.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Claims 1-4, 9, 13, 17-20, 22-23, 26-33 and 48-61 are rejected under 35 U.S.C. 112(b)as being indefinite for failing to particularly point out and distinctly claim the subject matter the invention. Dependent claims are rejected similarly, unless otherwise noted below. The following issues cause the respective claims to be rejected under 112(b) as indefinite:
The following recitations require but lack antecedent basis, rendering their claims indefinite because there is no previous recitations of the followings terms as written:
claim 1, "the geometric parameters"
claims 1 (step (b)(iii)), 22 (step (vi)) and 28, "the Euler cycle"
claim 1 (step (c)), "the sequences of the single-stranded RNA scaffold"
claim 17, "the crossover"
claims 17 and 23, "the length"
claim 22, "the vertices" (step (ii)), "the nodes" (step (ii)), "the graph" (step(ii)) and "the point" (step (iv))
claim 28, "the A-trail Euler circuit"
claim 29, "the three-dimensional structure"
claims 48, 51 and 54, "the group"
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-4, 9, 13, 17-20, 22-23, 26-33 and 48-61 are rejected under 35 USC § 101 because the claimed inventions are directed to one or more Judicial Exceptions (JEs) without significantly more. Regarding JEs, "Claims directed to nothing more than abstract ideas..., natural phenomena, and laws of nature are not eligible for patent protection" (MPEP 2106.04 §I). Abstract ideas include mathematical concepts and procedures for evaluating, analyzing or organizing information, which are a type of mental process (MPEP 2106.04(a)(2)).
101 background
MPEP 2106 organizes JE analysis into Steps 1, 2A (Prong One & Prong Two), and 2B as analyzed below. MPEP 2106 and the following USPTO website provide further explanation and case law citations: uspto.gov/patent/laws-and-regulations/examination-policy/examination-guidance-and-training-materials.
Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter (MPEP 2106.03)?
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
Analysis of instant claims
Step 1: Are the claims directed to a 101 process, machine, manufacture, or composition of matter (MPEP 2106.03)?
The instant claims are directed to a method (claims 1-4, 9, 13, 17-20, 22-23, 26-33 and 48-61) which falls within one of the categories of statutory subject matter.
[Step 1: claims 1-4, 9, 13, 17-20, 22-23, 26-33 and 48-61: Yes]
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
Background
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. MPEP § 2106.04(a)(2) further explains that abstract ideas are defined as:
• mathematical concepts (mathematical formulas or equations, mathematical relationships
and mathematical calculations) (MPEP 2106.04(a)(2)(I));
• certain methods of organizing human activity (fundamental economic principles or practices, managing personal behavior or relationships or interactions between people) (MPEP 2106.04(a)(2)(II)); and/or
• mental processes (concepts practically performed in the human mind, including observations, evaluations, judgments, and opinions) (MPEP 2106.04(a)(2)(III)).
Analysis of instant claims
With respect to the instant claims, under the Step 2A, Prong One evaluation, the claims are found to recite abstract ideas that fall into the grouping of mathematical concepts (in particular mathematical relationships and formulas) and mental processes (in particular procedures for observing, analyzing and organizing information) are as follows.
Mathematical concepts (in particular mathematical relationships and formulas) include:
• "(a) providing the geometric parameters of an input, wherein the input comprises a 3D polyhedral or 2D polygon geometric shape of an RNA nanostructure, and optionally one or more of its physical dimensions" (independent claim 1);
• "(i) rendering the geometric shape as a closed surface polyhedral network or an open surface polygonal network" (independent claim 1);
• "(ii) determining a spanning tree of the network" (independent claim 1);
• "(iii) calculating the Euler cycle of the network, wherein the Euler cycle represents the route of a single-stranded RNA scaffold that traces once along each edge in both directions throughout the entire geometric shape" (independent claim 1);
• "(i) rendering the geometric shape as a closed surface polyhedral network or an open surface polygonal network" (claim 22);
• "(ii) determining a spanning tree of the network, wherein the vertices and lines of the graph are the nodes and edges of the network, respectively" (claim 22);
• "(vi) calculating the Euler cycle of the network, wherein the Euler cycle represents the route of a single-stranded RNA scaffold that traces once along each edge in both directions throughout the entire geometric shape" (claim 22); and
• "(d) predicting the three-dimensional structure of the scaffolded RNA nanostructure" (claim 30).
The claims identified above read on math. The abstract ideas recited in the claims are evaluated under the Broadest Reasonable Interpretation and determined each element performed either in the mind and/or by mathematical operation. Without further detail as to the methodology involved in "calculating/designing RNA scaffold structures", under the BRI, the recitations identified above require mathematical techniques as the only supported embodiments. Further support for the mathematical techniques used in the claims is provided in the specification at pg. 111 para. 2, which discloses A-form design rules with staple crossover asymmetry implemented in a top-down design algorithm that calculates sequences for folding an input target shape with wireframe edges. Thus, the recited terms correspond to verbal equivalents of mathematical concepts because they constitute actions executed by a group of mathematical steps in a form of a mathematical algorithm; thus mathematical concepts (MPEP 2106.04(a)(2)). A mathematical concept need not be expressed in mathematical symbols, because "words used in a claim operating on data to solve a problem can serve the same purpose as a formula." In re Grams, 888 F.2d 835, 837 and n.1, 12 USPQ2d 1824, 1826 and n.1 (Fed. Cir. 1989). MPEP 2106.04(a)(2) pertains.
Mental processes, defined as concepts or steps practically performed in the human mind such as steps of observations, evaluations, judgments, analysis, opinions or organizing information include:
• "(b) identifying a route for a single-stranded RNA scaffold that traces throughout the geometric shape based on A-form helical nucleic acid geometry" (independent claim 1);
• "(c) generating the sequences of the single-stranded RNA scaffold and optionally the nucleic acid sequence of staple strands that combine to form a scaffolded RNA nanostructure having the geometric shape" (independent claim 1);
• "generating the sequences of staple strands that combine to form a scaffolded RNA nanostructure comprising staple crossover asymmetry, with 11 nucleotides per helical turn " (claim 2);
• "(iii) classifying each edge of the network based on its membership in the spanning tree, wherein edges that are members of the spanning tree do not have a scaffold double crossover, and edges that are not members of the spanning tree have a scaffold double crossover" (claim 22);
• "(iv) splitting each edge that is not a member of the spanning tree into two edges, each containing a pseudo-node at the point of the scaffold crossover" (claim 22);
• "(v) splitting each node at each of the vertices into two pseudo-nodes" (claim 22);
• "(e) assembling the scaffolded RNA nanostructure" (claim 31); and
• "(f) validating the scaffolded RNA nanostructure) (claim 32).
Under the BRI, the recited limitations are mental processes because a human mind is also sufficiently capable of integrating, eliminating data and arrange data presented to reduce visual overlap.
Dependent claims 3-4, 9, 13, 17-20, 23, 26-29, 33 and 48-61 recite further steps that limit the judicial exceptions in independent claim 1 and, as such, also are directed to those abstract ideas. For example, claims 3-4, 17-19 and 23 recite further details about the staple crossover asymmetry; claim 9 recites further details about step (a) for providing parameters; claim 13 recites further details about the geometry shape; claim 20 recites further details about the staples generated; claims 26-27 recite further details about the spanning tree; claim 28 recites further details about the Euler circuit; claim 29 recites further details about the rendering step; claim 33 recites further details about validating the scaffolded RNA; and claims 48-61 recite further details about the RNA scaffold nanostructure.
[Step 2A Prong One: claims 1-4, 9, 13, 17-20, 22-23, 26-33 and 48-61: Yes ]
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Background
MPEP 2106.04(d).I lists the following example considerations for evaluating whether a judicial exception is integrated into a practical application:
An improvement in the functioning of a computer or an improvement to other technology or another technical field, as discussed in MPEP §§ 2106.04(d)(1) and 2106.05(a);
Applying or using a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition, as discussed in MPEP § 2106.04(d)(2);
Implementing a judicial exception with, or using a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim, as discussed in MPEP § 2106.05(b);
Effecting a transformation or reduction of a particular article to a different state or thing, as discussed in MPEP § 2106.05(c); and
Applying or using the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception, as discussed in MPEP § 2106.05(e).
Analysis of instant claims
Instant claim 61 recite additional elements that are not abstract ideas:
• "synthesizing the RNA scaffold sequence by a method comprising in vitro transcription" (claim 61);
Considerations under Step 2A, Prong Two
The recited limitations in claims 1-4, 9, 13, 17-20, 22-23, 26-33 and 48-61 are interpreted as requiring the use of a computer as disclosed in this instant specification at pg. 30 para. 3, pg. 35 para. 6, pg. 37 para. 5 and pg. 58 para. 1. Hence, the claims explicitly recite steps executed by computers and therefore can be described as computer functions or instructions to implement on a generic computer.
Further steps directed to additional non-abstract elements of a computing device/computer do not describe any specific computational steps by which the "computer parts" perform or carry out the judicial exceptions, nor do they provide any details of how specific structures of the computer are used to implement these functions. The claims state nothing more than a generic computer which performs the functions that constitute the judicial exceptions.
The judicial exceptions in the claims are considered to perform the claimed abstract idea with a computer, which is not sufficient to integrate an abstract idea into a practical application (see MPEP 2106.05(f)); since steps that can be performed mentally and merely performing the mental process in a computer environment do not negate the fact that something that can be carried out in the human mind. See MPEP 2106.04(a)(2).III.C.
The recited "synthesizing" step reads on a generic "apply it" step because the claim recites an idea of a solution or outcome without any indication of how the judicial exception impacts or influences this step. There are no additional limitations to indicate details of exactly how the judicial exception is being integrated into the recited step of synthesizing. There are no additional limitations to indicate that the claimed computer, processor, or computer readable medium require anything other than generic computer components in order to carry out the recited abstract idea in the claims. Claims that amount to instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible. Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984. MPEP 2106.05(b).
Hence, these are mere instructions to apply the abstract idea using a computer and insignificant extra-solution activity and therefore the claims do not integrate that abstract idea into a practical application (see MPEP 2106.04(d) § I; 2106.05(f); and 2106.05(g)).
In Step 2A, Prong One above, claim steps and/or elements were identified as part of one or more judicial exceptions (JEs).
In this Step 2A, Prong Two immediately above claim steps and/or elements were identified as part of one or more additional elements. Additional elements are further discussed in Step 2B below.
Here in Step 2A, Prong Two, no additional step or element clearly demonstrates integration of the JE(s) into a practical application.
[Step 2A Prong Two: claims 1-4, 9, 13, 17-20, 22-23, 26-33 and 48-61: No]
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
According to analysis so far, the additional elements described above do not provide significantly more than the judicial exception. A determination of whether additional elements provide significantly more also rests on whether the additional elements or a combination of elements represents other than what is well-understood, routine, and conventional. Conventionality is a question of fact and may be evidenced as: a citation to an express statement in the specification or to a statement made by an applicant during examination that demonstrates a well-understood, routine or conventional nature of the additional element(s); a citation to one or more of the court decisions as discussed in MPEP 2106(d)(II) as noting the well-understood, routine, conventional nature of the additional element(s); a citation to a publication that demonstrates the well-understood, routine, conventional nature of the additional element(s); and/or a statement that the examiner is taking official notice with respect to the well-understood, routine, conventional nature of the additional element(s).
Claims 1-4, 9, 13, 17-20, 22-23, 26-33 and 48-61 recite a computer or computer functions, interpreted as instructions to apply the abstract idea using a computer, where the computer does not impose meaningful limitations on the judicial exceptions; which can be performed without the use of a computer (MPEP 2106.04(d) § I; and MPEP 2106.05(f)).
With respect to the instant claims, the prior art review to Jedrzejczyk ("Designing synthetic RNA for delivery by nanoparticles." Journal of Physics: Condensed Matter 29(12):123001 (2017)), newly cited) discloses that using rational RNA structural design and synthesis of new RNA nano-objects based on RNA folding and determination of structure is routine, well-understood and conventional in the art. Said portions of the prior art are, for example, pg. 3 col. 2 para. 3
When the claims are considered as a whole, they do not integrate the abstract idea into a practical application; they do not confine the use of the abstract idea to a particular technology; they do not solve a problem rooted in or arising from the use of a particular technology; they do not improve a technology by allowing the technology to perform a function that it previously was not capable of performing; and they do not provide any limitations beyond generally linking the use of the abstract idea to a broad technological environment. See MPEP 2106.05(a) and 2106.05(h).
The instant claims constitute insignificant extra solution activity, and when considered individually, are insufficient to constitute inventive concepts that would render the claims significantly more than an abstract idea (see MPEP 2106.05(g)). Hence, these elements, when considered individually, are insufficient to constitute inventive concepts that would render the claims significantly more than an abstract idea (see MPEP 2106.05(d)).
[Step 2B: claims 1-4, 9, 13, 17-20, 22-23, 26-33 and 48-61: No]
Conclusion: Instant claims are directed to non-statutory subject matter
For the reasons above, the claims in this instant application, when the limitations are considered individually and as a whole, are directed to an abstract idea and lack an inventive concept not clearly anything significantly more.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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.
A. Claims 1-4, 9, 13, 19, 26, 28 and 30-33 are rejected under 35 U.S.C. 103(a) as being unpatentable over Elonen ("Algorithmic design of RNA polyhedra." Thesis dissertation - Aalto University (2018)) in view of Benson ("DNA rendering of polyhedral meshes at the nanoscale." Nature 523.7561:441-444 (2015)), as cited on the attached Form PTO-892.
Claim 1 recites:
(a) providing the geometric parameters of an input, wherein the input comprises a 3D polyhedral or 2D polygon geometric shape of an RNA nanostructure, and optionally one or more of its physical dimensions;
(b) identifying a route for a single-stranded RNA scaffold that traces throughout the geometric shape based on A-form helical nucleic acid geometry wherein identifying a route for a single-stranded RNA scaffold that traces throughout the geometric shape in step (b) comprises the steps of:
(i) rendering the geometric shape as a closed surface polyhedral network or an open surface polygonal network;
(ii) determining a spanning tree of the network;
(iii) calculating the Euler cycle of the network, wherein the Euler cycle represents the route of a single-stranded RNA scaffold that traces once along each edge in both directions throughout the entire geometric shape; and
(c) generating the sequences of the single-stranded RNA scaffold and optionally the nucleic acid sequence of staple strands that combine to form a scaffolded RNA nanostructure having the geometric shape
• Elonen teaches the design and simulation of single stranded RNA polyhedral (pg. 9 para. 5); wherein the input to the algorithm is any single polyhedron (i.e. step (a)) (pg. 33 para. 3) used for converting polyhedra to RNA strands (pg. 32 para. 1); wherein a sorting algorithm routes a strand around any spanning tree (i.e. (ii) determining a spanning tree of the network) to find an unknotted path around a polyhedron (i.e. (b) identifying a route for a single-stranded RNA scaffold that traces throughout the geometric shape) (pg. 9 para. 2); wherein RNA are naturally helical and all RNA helices are considered to be of the A-form, which is the most common form in nature (i.e. based on A-form helical nucleic acid geometry) (pg. 9 para. 1); wherein the algorithm combs across the spheres surface from one pole to the other until it reaches the starting point again where a sphere can be mapped to a plane by puncturing a hole in it and by stretching it across the plane, i.e., the non-crossing cycle on the sphere will be non-crossing also on a plane (i.e. (i) rendering the geometric shape as an open surface polygonal network) (pg. 19 para. 1); wherein the designed RNA primary structure, i.e., the final sequence itself, from its secondary structure is generated (i.e. (c) generating the sequences of the single-stranded RNA scaffold) (pg. 24 para. 1). It is interpreted that the recited "optionally one or more of its physical dimensions" and "optionally the nucleic acid sequence of staple strands that combine to form a scaffolded RNA nanostructure having the geometric shape" constitutes a non-requirement since the claim does not require such one or more of its physical dimensions.
(iii) calculating the Euler cycle of the network, wherein the Euler cycle represents the route of a single-stranded RNA scaffold that traces once along each edge in both directions throughout the entire geometric shape
• Elonen does not teach the recitation above. However, Benson teaches a general method of folding arbitrary polygonal digital meshes in DNA (i.e. reading on nucleic acid sequences) that readily produces structures (pg. 441 col. 1 para. 1); wherein having selected a target 3D polygon mesh in the design step, the first condition for a triangulated mesh to be routable with the scaffold strand traversing every edge once, is that the mesh graph must admit an Eulerian circuit (pg. 442 col. 1 para. 2); wherein the proposed method adopted routeing based on A-trails, a specific type of Eulerian circuit (pg. 442 col. 1 para. 3); wherein the algorithm managed to find a routeing for all the designed meshes within seconds (i.e. (iii) calculating the Euler cycle of the network, wherein the Euler cycle represents the route of a single-stranded RNA scaffold that traces once along each edge in both directions throughout the entire geometric shape) (pg. 442 col. 2 para. 1).
Claim 2 recites:
wherein generating the sequences of the single-stranded RNA scaffold in step (c) comprises generating the sequences of staple strands that combine to form a scaffolded RNA nanostructure comprising staple crossover asymmetry, with 11 nucleotides per helical turn
• Elonen does not teach the recitation above. However, Benson teaches the use of staple strands sequences used in the in the design process (Methods pg. 2 col. 1 para. 4) for creating DNA origami polygonal (pg. 441 col. 1 para. 1); wherein all RNA helices are considered A-form (pg. 14 para. 1) with the helicity parameter set to 11 base pairs (i.e. 11 nucleotides in each strand per helical turn) (pg. 13 Table 2.2).
Claim 3 recites:
wherein the staple crossover asymmetry comprises a difference in the nucleotide position across two helices of an edge of from one to ten nucleotides, inclusive (c) generating the sequences of the single-stranded RNA scaffold and optionally the nucleic acid sequence of staple strands that combine to form a scaffolded RNA nanostructure having the geometric shape
Claim 4 recites:
wherein the staple crossover asymmetry comprises a difference in the nucleotide position across two helices of an edge of four nucleotides
• Elonen does not teach the recitation above. However, Benson teaches the use of staple strands sequences used in the in the design process (Methods pg. 2 col. 1 para. 4) for creating DNA origami polygonal (pg. 441 col. 1 para. 1); wherein optimal length of edges are discretized into steps of 5 nucleotides, where with an odd multiple of 5 nucleotides, a crossing occurs. (i.e. a 5 nucleotide offset between crossover positions across an edge as in claims 3 and 4) (Supplemental Information pg. 11 para. 2); wherein the routeing of the staple strands are the helper DNA oligonucleotides that drive DNA-origami folding by completing the edge connection at the vertices (i.e. generating the sequences of staple strands that combine to form a scaffolded nanostructure comprising staple crossover asymmetry) (pg. 442 col. 2 para. 2).
• Benson teaches a 5 nucleotide offset between crossover positions across an edge which makes obvious the instantly claimed "difference in the nucleotide position across two helices of an edge of from one to ten nucleotides" and "a difference in the nucleotide position across two helices of an edge of four nucleotides." It would have been prima facie obvious to one of ordinary skill in the art to select any portions of the disclosed ranges including the instantly claimed ranges from the ranges disclosed in the prior art references, particularly in view of the fact that: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set percentage ranges is the optimum combination of percentages" In re Peterson 65 USPQ2d 1379 (CAFC 2003). See also In re Malagari, 182 USPQ 549,533 (CCPA 1974) and MPEP 2144.05 modifying the values for identity, coverage and e-value would improve the quality of the data being filtered for the database created since it would yield more complete sequences (with less sequences overlaps when it comes to e-values) being identified by the method.
Claim 9 recites:
wherein the input in step (a) further comprises one or more of the geometric shape's physical dimensions
• Elonen does not teach the recitation above. However, Benson teaches scaling the structures to scaffold sizes of between six and eight thousand nucleotides (pg. 443 col. 1 para. 4); wherein the scaling (physical dimension) of each 3D model can be set arbitrarily before the relaxation simulation and will determine the double-helix characteristics at each edge (pg. 443 col. 1 para. 4)
Claim 13 recites:
wherein the geometric shape does not have spherical topology
• Elonen does not teach the recitation above. However, Benson teaches target 3D geometries rendered with DNA automatically, with fine-grained control over the design in a graphical user interface before sequence generation (pg. 443 col. 1 para. 3); wherein six polyhedral models were designed: a ball, a nicked torus, a helix, a rod, a humanoid stickman (i.e. reading on a non-spherical topology), a soda bottle and a bunny (pg. 443 col. 1 para. 4).
Claim 19 recites:
wherein the staples are DNA
• Elonen does not teach the recitation above. However, Benson teaches the use of staple strands sequences used in the in the design process (Methods pg. 2 col. 1 para. 4) for creating DNA origami polygonal (pg. 441 col. 1 para. 1).
Claim 26 recites:
wherein the spanning tree of the network is determined using a breadth-first search or depth-first search
• Elonen teaches the spanning tree path-tracing done by the way of a depth first search, where the next vertex is always chosen in such a way as to avoid topological knots (pg. 18 para. 2).
Claim 28 recites:
wherein the Euler circuit is the A-trail Euler circuit
• Elonen does not teach the recitation above. However, Benson teaches a general method of folding arbitrary polygonal digital meshes in DNA (i.e. reading on nucleic acid sequences) that readily produces structures (pg. 441 col. 1 para. 1); wherein the proposed method adopted routeing based on A-trails, a specific type of Eulerian circuit (pg. 442 col. 1 para. 3).
Claim 30 recites:
further comprising the step of: (d) predicting the three-dimensional structure of the scaffolded RNA nanostructure
• Elonen teaches the design and simulation of single stranded RNA polyhedral (i.e. predicting the three-dimensional structure) (pg. 9 para. 5); wherein the input to the algorithm is any single polyhedron (i.e. step (a)) (pg. 33 para. 3) used for converting polyhedra to RNA strands (pg. 32 para. 1); for the design and synthesize of nano-scale objects with RNA (i.e. scaffolded RNA nanostructure) (pg. 46 para. 1)
Claim 31 recites:
further comprising the step of: (e) assembling the scaffolded RNA nanostructure
• Elonen teaches the design and simulation of single stranded RNA polyhedral (i.e. predicting the three-dimensional structure) (pg. 9 para. 5); wherein the input to the algorithm is any single polyhedron (i.e. step (a)) (pg. 33 para. 3) used for converting polyhedra to RNA strands (pg. 32 para. 1); for the design and synthesize of nano-scale objects with RNA (i.e. scaffolded RNA nanostructure) (pg. 46 para. 1); wherein the RNA-based bottom-up nanotechnology (pg. 45 para. 1) was used to create nanostructures through the self-assembly - synthesis of nanoscale building blocks (pg. 7 para. 2).
Claim 32 recites:
further comprising the step of: (f) validating the scaffolded RNA nanostructure
Claim 33 recites:
wherein the scaffolded RNA nanostructure is validated by comparison with a predicted three-dimensional structure
• Elonen teaches the design and simulation of single stranded RNA polyhedral (i.e. predicting the three-dimensional structure) (pg. 9 para. 5); wherein the input to the algorithm is any single polyhedron (i.e. step (a)) (pg. 33 para. 3) used for converting polyhedra to RNA strands (pg. 32 para. 1); for the design and synthesize of nano-scale objects with RNA (i.e. scaffolded RNA nanostructure) (pg. 46 para. 1); wherein, after the generation of primary structures, they were validated against computer simulations (i.e. validated by comparison with a predicted three-dimensional structure as in claims 32-33) (pg. 30 para. 4) and transcribed from a synthesized DNA strand (pg. 30 para. 5).
Rationale for combining (MPEP §2142-2143)
Regarding claims 1-4, 9, 13, 19, 26, 28 and 30-33, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the methods of Elonen in view of Benson because all references disclose methods for designing scaffolded nucleic acid nanostructures. The motivation would have been to incorporate an effective branch-and-bound search algorithm that makes it feasible to find the requisite scaffold routings quickly, even in 3D designs with a large polygon count (pg. 444 col. 1 para. 2 Benson).
Therefore it would have been obvious to one of ordinary skill in the art to substitute designing scaffolded nucleic acid nanostructures method of Elonen to the methods by Benson because such a substitution is no more than the simple substitution of one known element for another. One of ordinary skill in the art would be able to motivated to combine the teachings in these references with a reasonable expectation of success since the described teachings pertain to methods for designing scaffolded nucleic acid nanostructures.
B. Claims 17-18 are rejected under 35 U.S.C. 103(a) as being unpatentable over Elonen and Benson as applied to claim 1 above further in view of Sparvath ("Computer-aided design of RNA origami structures." 3D DNA Nanostructure: Methods and Protocols. New York, NY: Springer New York 51-80 (2016)), as cited on the attached Form PTO-892.
Claim 17 recites:
wherein the crossover type is anti-parallel crossover, wherein the length of each edge is expressed as a multiple of 11 base pairs, and wherein the length of each edge is between 22 base pairs and 1,100 base pairs, inclusive
Claim 18 recites:
wherein the length of each edge is 44 base pairs, 55 base pairs, 66 base pairs, or 77 base pairs
• Elonen teaches scale-factor it determines how many bases are placed on each edge (pg. 20 para. 3); wherein since twist for A-form helices is 32.73° for a cylinder shape, the scale factor defines the number of bases as a multiple of 11 (i.e. wherein the length of each edge is expressed as a multiple of 11 base pairs) (pg. 22 para. 1).
• Elonen does not teach the "anti-parallel crossover." However, Benson teaches the stapling being designed so that when the scaffold strand hybridizes with the antiparallel staples, the entire structure folds into the required polyhedral beam framework.
• Neither Elonen or Benson teach "wherein the length of each edge is between 22 base pairs and 1,100 base pairs, inclusive." However, Sparvath teaches generating a 44 base pair RNA double helix made of 4 helix turns (i.e. 44 base pair edge – multiple of 22 - as in claims 17-18) (pg. 59 para. 5)
Rationale for combining (MPEP §2142-2143)
Regarding claims 17-18, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the methods of Elonen and Benson in view of Sparvath because all references disclose methods for designing scaffolded RNA nanostructures. The motivation would have been to incorporate a detailed protocol for the single-stranded RNA origami design and use computer programs to design RNA sequences that are compatible with the structure (pg. 1 Abstract Sparvath).
Therefore it would have been obvious to one of ordinary skill in the art to substitute designing scaffolded RNA nanostructures method of Elonen and Benson to the methods by Sparvath because such a substitution is no more than the simple substitution of one known element for another. One of ordinary skill in the art would be able to motivated to combine the teachings in these references with a reasonable expectation of success since the described teachings pertain to methods for designing scaffolded RNA nanostructures.
C. Claim 20 is rejected under 35 U.S.C. 103(a) as being unpatentable over Elonen and Benson as applied to claim 1 above further in view of Torelli ("Isothermal folding of a light-up bio-orthogonal RNA origami nanoribbon." Scientific Reports 8(1):6989 (2018)), as cited on the attached Form PTO-892.
Claim 20 recites:
wherein the staples are RNA
• Neither Elonen or Benson teach the recitation above. However, Torelli teaches RNA scaffold and the complementary staples folding in a physiologically compatible isothermal condition (pg. 1 para. 1).
Rationale for combining (MPEP §2142-2143)
Regarding claim 20, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the methods of Elonen and Benson in view of Torelli because all references disclose methods for designing scaffolded RNA nanostructures. The motivation would have been to incorporate RNA origami nanostructure as an useful platform to organize new genetic control system (pg. 8 para. 5 Torelli).
Therefore it would have been obvious to one of ordinary skill in the art to substitute designing scaffolded RNA nanostructures method of Elonen and Benson to the methods by Torelli because such a substitution is no more than the simple substitution of one known element for another. One of ordinary skill in the art would be able to motivated to combine the teachings in these references with a reasonable expectation of success since the described teachings pertain to methods for designing scaffolded RNA nanostructures.
D. Claims 22, 27 and 29 are rejected under 35 U.S.C. 103(a) as being unpatentable over Elonen and Benson as applied to claims 1 and 26 above further in view of Ratanalert ("Sequence design principles for 3D wireframe DNA origami." Dissertation. Massachusetts Institute of Technology, 2018), as cited on the attached Form PTO-892.
Claim 22 recites:
(i) rendering the geometric shape as a closed surface polyhedral network or an open surface polygonal network;
• Elonen teaches the design and simulation of single stranded RNA polyhedral (pg. 9 para. 5); wherein the algorithm combs across the spheres surface from one pole to the other until it reaches the starting point again where a sphere can be mapped to a plane by puncturing a hole in it and by stretching it across the plane, i.e., the non-crossing cycle on the sphere will be non-crossing also on a plane (i.e. (i) rendering the geometric shape as an open surface polygonal network) (pg. 19 para. 1).
(ii) determining a spanning tree of the network, wherein the vertices and lines of the graph are the nodes and edges of the network, respectively;
• Elonen does not teach the recitation above. However, Benson teaches generating Eulerian circuits for 3D polyhedra by deriving the polyhedral graph, then identifying the odd degree nodes, pairing them and doubling the edges along each path connecting the designated pair to obtain the Eulerian graph where nodes are depicted as vertices and edges are depicted as lines (Supplemental Information pg. 4 Fig. S1.1); wherein the Eulerian circuit in a derived graph resulted from the search tree based on binary choices for vertices (pg. Methods pg. 1 para. 9)
(iii) classifying each edge of the network based on its membership in the spanning tree, wherein edges that are members of the spanning tree do not have a scaffold double crossover, and edges that are not members of the spanning tree have a scaffold double crossover;
• Elonen does not teach the recitation above. However, Benson teaches the Eulerian circuit in a derived graph results from the search tree based on binary choices for vertices (pg. Methods pg. 1 para. 9); wherein the optimal length of edges is discretized into steps of 5 nucleotides, where if the length of the edge is an even multiple of 5 nucleotides, the endpoint nucleotides that belong to one strand will end up on the same side of a half plane dividing the helix along its axis and a crossing will not occur but if the length of the edge is an odd multiple of 5 nucleotides, a crossing occurs (i.e. step (iii)); wherein the difference between a non-crossing and crossing routing is depicted in Fig. S2.1a and S2.1b (Supplemental Information pg. 1 para. 2).
(iv) splitting each edge that is not a member of the spanning tree into two edges, each containing a pseudo-node at the point of the scaffold crossover;
(v) splitting each node at each of the vertices into two pseudo-nodes; and
(vi) calculating the Euler cycle of the network, wherein the Euler cycle represents the route of a single-stranded RNA scaffold that traces once along each edge in both directions throughout the entire geometric shape
• Neither Elonen or Benson teach the recitation above. However, Ratanalert teaches rendering arbitrary geometries as node-edge networks based on the double crossovers-based wireframe motif (pg. 29 para. 2); wherein once the spanning tree has been determined, the graph needs to be converted to an Eulerian circuit (pg. 39 para. 3); wherein first, for each edge that is not in the spanning tree, a pair of pseudo-nodes is added to split the edge into two halves, each corresponding to one side of a scaffold crossover then, for each vertex in the graph, a set of pseudo-nodes is added to replace the vertex node (i.e. steps (iv)-(v)) (pg. 39 para. 4); wherein for each face, a pseudo-node is placed that joins the two bordering edges and disconnects them from the other edges and after all pseudo-nodes are placed for all vertices, the original vertex nodes are no longer part of the graph, and each edge is now bounded on both ends by pseudo-nodes; which defines the Eulerian circuit through which the scaffold will be routed (i.e. steps (vi)) (pg. 39 para. 4).
Claim 27 recites:
wherein the spanning tree is calculated using Prim's formula or Kruskal's formula
• Neither Elonen or Benson teach the recitation above. However, Ratanalert teaches generating a spanning tree, where solving the scaffold routing problem is identical to solving for a spanning tree of the structure (pg. 38 para. 4); wherein given a network, Prim's algorithm can be used to find the minimum weight spanning tree (pg. 38 para. 4).
Claim 29 recites:
wherein rendering the geometric shape as polyhedral network comprises producing a node-edge network of the three-dimensional structure
• Neither Elonen or Benson teach the recitation above. However, Ratanalert teaches 3D wireframe structures in which two double helices, joined by double crossovers or parallel crossovers, form a 3D network as its edges (pg. 25 para. 2); wherein rendering arbitrary geometries as node-edge networks are based on the double crossovers-based wireframe motif (pg. 29 para. 2).
Rationale for combining (MPEP §2142-2143)
Regarding claims 22, 27 and 29, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the methods of Elonen and Benson in view of Ratanalert because all references disclose methods for designing scaffolded nucleic acid nanostructures. The motivation would have been to create algorithms to enable autonomous top-down design of nucleic acid structures (pg. 25 para. 3 Ratanalert) and incorporate features essential to biomolecular applications that use spatially specific asymmetric sequence programming for protein or RNA scaffolding, as well as other chemical functionalization (pg. 33 para. 1 Ratanalert).
Therefore it would have been obvious to one of ordinary skill in the art to substitute designing scaffolded nucleic acid nanostructures method of Elonen and Benson to the methods by Ratanalert because such a substitution is no more than the simple substitution of one known element for another. One of ordinary skill in the art would be able to motivated to combine the teachings in these references with a reasonable expectation of success since the described teachings pertain to methods for designing scaffolded nucleic acid nanostructures.
E. Claim 23 is rejected under 35 U.S.C. 103(a) as being unpatentable over Elonen, Benson and Ratanalert as applied to claims 1 and 22 above further in view of Sparvath as cited on the attached Form PTO-892.
Claim 23 recites:
wherein the crossover type is parallel crossover, and wherein the length of each edge is between 22 base pairs and 1,100 base pairs, inclusive
• Neither Elonen or Benson or Ratanalert teach the recitation above. However, Sparvath teaches the RNA origami method that uses double-crossovers to arrange the RNA helices in parallel to each other using multiple strands (pg. 52 para. 3); wherein a 44 base pair RNA double helix made of 4 helix turns was generated (i.e. 44 base pair edge – length of each edge is between 22 base pairs and 1,100 base pairs) (pg. 59 para. 5).
Rationale for combining (MPEP §2142-2143)
Regarding claim 23, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the methods of Elonen, Benson and Ratanalert in view of Sparvath because all references disclose methods for designing scaffolded RNA nanostructures. The motivation would have been to incorporate a detailed protocol for the single-stranded RNA origami design and use computer programs to design RNA sequences that are compatible with the structure (pg. 1 Abstract Sparvath).
Therefore it would have been obvious to one of ordinary skill in the art to substitute designing scaffolded RNA nanostructures method of Elonen, Benson and Ratanalert to the methods by Sparvath because such a substitution is no more than the simple substitution of one known element for another. One of ordinary skill in the art would be able to motivated to combine the teachings in these references with a reasonable expectation of success since the described teachings pertain to methods for designing scaffolded RNA nanostructures.
F. Claims 48-53 and 60 are rejected under 35 U.S.C. 103(a) as being unpatentable over Elonen and Benson as applied to claim 1 above further in view of Sahin ("An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma." Nature 585.7823:107-112 (2020)), as cited on the attached Form PTO-892.
Claim 48 recites:
wherein the RNA scaffold comprises one or more selected from the group consisting of messenger RNA (mRNA), replicating RNA (repRNA), guide-strand RNA (gsRNA), ribosomal RNA (rRNA), transfer RNA (tRNA), genomic transcript RNA, aptamer RNA and functional RNA(s).
Claim 49 recites:
wherein the RNA scaffold comprises messenger RNA (mRNA) encoding one or more polypeptides or proteins
Claim 50 recites:
wherein the messenger RNA (mRNA) encodes one or more polypeptide or protein antigens
Claim 51 recites:
wherein the antigen is selected from the group consisting of a viral antigen, bacterial antigen, protozoan antigen, environmental allergen, food allergen and tumor antigen
Claim 52 recites:
wherein the messenger RNA (mRNA) encodes one or more enzymes, fluorescent proteins or antigen-binding proteins
• Neither Elonen or Benson teach the recitation above. However, Sahin teaches an nanoparticulate liposomal RNA vaccine (pg. 107 col. 1 para. 2) assembled with messenger RNAs (i.e. RNA scaffold comprising messenger RNA as in claim 48), encoding four tumour- associated antigens (i.e. messenger RNA (mRNA) encodes one or more polypeptide or protein antigens as in claim 50 wherein the antigen is a tumor antigen as in claim 51) - specifically, NY- ESO-1, MAGEA3, tyrosinase (i.e. messenger RNA (mRNA) encoding an enzyme as in claim 52) and TPTE (i.e. messenger RNA (mRNA) encoding one or more polypeptides or proteins as in claim 49) (pg. 107 col. 2 para. 2).
Claim 53 recites:
wherein the messenger RNA (mRNA) encodes the prokaryotic green fluorescent protein (GFP) protein
• Neither Elonen or Benson teach the recitation above. However, Sahin teaches an nanoparticulate liposomal RNA vaccine (pg. 107 col. 1 para. 2) assembled with messenger RNAs encoding vaccine antigens, enhanced green fluorescent protein (eGFP), influenza matrix protein 1 (M1) or tetanus p2/p16 sequences (Methods pg. 2 col. 1 para. 3).
Claim 60 recites:
further comprising formulating the scaffolded RNA nanostructure into a vaccine
• Neither Elonen or Benson teach the recitation above. However, Sahin teaches an nanoparticulate liposomal RNA vaccine (pg. 107 col. 1 para. 2) assembled with messenger RNAs that encoding four tumour- associated antigens (pg. 107 col. 2 para. 2).
Rationale for combining (MPEP §2142-2143)
Regarding claims 48-53 and 60, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the methods of Elonen and Benson in view of Sahin because all references disclose methods for designing scaffolded RNA nanostructures. The motivation would have been to incorporate a potent RNA based immunotherapy with tumor antigens as targets for cancer vaccination (pg. 107 Abstract Sahin).
Therefore it would have been obvious to one of ordinary skill in the art to substitute designing scaffolded RNA nanostructures method of Elonen and Benson to the methods by Sahin because such a substitution is no more than the simple substitution of one known element for another. One of ordinary skill in the art would be able to motivated to combine the teachings in these references with a reasonable expectation of success since the described teachings pertain to methods for designing scaffolded RNA nanostructures.
G. Claim 54 is rejected under 35 U.S.C. 103(a) as being unpatentable over Elonen, Benson and Sahin as applied to claim 1 and 48 above further in view of Sparvath as cited on the attached Form PTO-892.
Claim 54 recites:
wherein the RNA scaffold comprises a functional RNA selected from the group consisting of antisense molecules, silencing RNA (siRNA), micro RNA (miRNA), ribozymes, riboswitches, short hairpin RNA (shRNA), triplex forming RNA, and interfering RNA (RNAi).
• Neither Elonen or Benson or Sahin teach the recitation above. However, Sparvath teaches that RNA origami structures provide a stable framework that can be decorated with functional RNA elements such as riboswitches, ribozymes, interaction sites, and aptamers for binding small molecules or protein targets (pg. 51 Abstract).
Rationale for combining (MPEP §2142-2143)
Regarding claim 54, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the methods of Elonen, Benson and Sahin in view of Sparvath because all references disclose methods for designing scaffolded RNA nanostructures. The motivation would have been to incorporate a detailed protocol for the single-stranded RNA origami design and use computer programs to design RNA sequences that are compatible with the structure (pg. 1 Abstract Sparvath).
Therefore it would have been obvious to one of ordinary skill in the art to substitute designing scaffolded RNA nanostructures method of Elonen, Benson and Sahin to the methods by Sparvath because such a substitution is no more than the simple substitution of one known element for another. One of ordinary skill in the art would be able to motivated to combine the teachings in these references with a reasonable expectation of success since the described teachings pertain to methods for designing scaffolded RNA nanostructures.
H. Claims 55-57 are rejected under 35 U.S.C. 103(a) as being unpatentable over Elonen and Benson as applied to claim 1 above further in view Zhao ("Non-Viral Intracellular mRNA Delivery to Hard-To-Transfect Cells Using Synthetic Lipidoid Nanoparticles." Dissertation. Tufts University, 2020), as cited on the attached Form PTO-892.
Claim 55 recites:
wherein the RNA scaffold and/or staple sequences include one or more modified nucleotides
Claim 56 recites:
wherein the modified nucleotides reduce or prevent degradation of the modified RNA by RNAse enzymes
Claim 57 recites:
wherein the one or more modified nucleotides comprises 2'-fluorinated deoxy-uridine, or 2'- fluorinated deoxy-cytosine, or 5-methoxyuridine
• Neither Elonen or Benson teach the recitation above. However, Zhao teaches the application of nanotechnology in mRNA therapeutics (pg. 1 para. 1); wherein mRNA protection keeps it from RNAase degradation (i.e. modified nucleotides reduce or prevent degradation of the modified RNA by RNAse enzymes as in claim 56) (pg. 1 para. 1); wherein several chemical modifications of mRNA address degradation (i.e. RNA scaffold and/or staple sequences include one or more modified nucleotides as in claim 55) such as base moiety (ex: 5-methylcytosine, pseudouridine, 5-methoxyuridine) (i.e. 5-methoxyuridine modification as in claim 57) (pg. 10 para. 2)
Rationale for combining (MPEP §2142-2143)
Regarding claims 55-57, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the methods of Elonen and Benson in view of Zhao because all references disclose methods for designing scaffolded RNA nanostructures. The motivation would have been to incorporate an efficient mRNA delivery system in vitro and in-vivo (pg. ii para. 2 Zhao).
Therefore it would have been obvious to one of ordinary skill in the art to substitute designing scaffolded RNA nanostructures method of Elonen and Benson to the methods by Zhao because such a substitution is no more than the simple substitution of one known element for another. One of ordinary skill in the art would be able to motivated to combine the teachings in these references with a reasonable expectation of success since the described teachings pertain to methods for designing scaffolded RNA nanostructures.
I. Claims 58-59 and 61 are rejected under 35 U.S.C. 103(a) as being unpatentable over Elonen and Benson as applied to claims 1 and 31 above further in view of Agarwal ("Enzyme-driven assembly and disassembly of hybrid DNA–RNA nanotubes." Journal of the American Chemical Society 141(19):7831-7841 (2019)), as cited on the attached Form PTO-892.
Claim 58 recites:
wherein nanostructure comprises one or more RNA/DNA hybrid regions
Claim 59 recites:
wherein one or more of the RNA/DNA hybrid regions facilitates release of the scaffold RNA and/or one or more cargo molecules in the presence of an RNA/DNA hybrid specific nuclease
• Neither Elonen or Benson teach the recitation above. However, Agarwal teaches DNA-RNA nanotube system (i.e. nanostructure comprises one or more RNA/DNA hybrid regions as in claim 58) whose assembly and disassembly can be controlled using transcriptional programs where nanotubes assemble when inert DNA monomers are directly and selectively activated by RNA molecules that become embedded in the structure (pg. 7831 Abstract); wherein disassembly of filaments can be induced by an RNA-degrading enzyme (i.e. release of the scaffold RNA and/or one or more cargo molecules in the presence of an RNA/DNA hybrid specific nuclease as in claim 59) (pg. 7832 col. 1 para. 2); wherein RNAase (i.e. specific nuclease) participate in enzyme-mediated control of assembly and disassembly of hybrid DNA/RNA tubes (pg. 7835 Fig. 4).
Claim 61 recites:
wherein assembling the scaffolded RNA nanostructure comprises synthesizing the RNA scaffold sequence by a method comprising in vitro transcription
• Neither Elonen or Benson teach the recitation above. However, Agarwal teaches the assembly and disassembly of DNA/RNA nanotubes under different transcription and degradation conditions (pg. 7835 Fig. 4).
Rationale for combining (MPEP §2142-2143)
Regarding claims 58-59 and 61, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the methods of Elonen and Benson in view of Agarwal because all references disclose methods for designing scaffolded nucleic acid nanostructures. The motivation would have been to combine the natural functionalities of RNA molecules with the stability and predictability of DNA self-assembled systems (pg. 7832 col. 1 para. 2 Agarwal).
Therefore it would have been obvious to one of ordinary skill in the art to substitute designing scaffolded nucleic acid nanostructures method of Elonen and Benson to the methods by Agarwal because such a substitution is no more than the simple substitution of one known element for another. One of ordinary skill in the art would be able to motivated to combine the teachings in these references with a reasonable expectation of success since the described teachings pertain to methods for designing scaffolded nucleic acid nanostructures.
Conclusion
No claims are allowed.
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/F.F.L./Examiner, Art Unit 1685
/JANNA NICOLE SCHULTZHAUS/Examiner, Art Unit 1685
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