DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 168-187 were previously pending.
Receipt is acknowledged of the claim amendments submitted on 03 August 2026. Claims 182-183, and 185-187 are amended. Claims 169-171, 173, and 177-181 are canceled. Claims 188-196 are newly added.
Applicant’s election without traverse of the invention of group VI (claims 182-187) in the reply filed on 10 March, 2026 was previously acknowledged.
Claims 168, 172, and 174-176 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Therefore, claims 168, 172, 174-176, and 182-196 are pending and claims 182-196 are under examination in the present Official Action.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/EP2022/052145, filed 28 January, 2022, which claims priority to United Kingdom of Great Britain and Northern Ireland Application Nos. GB2102301.6, and GB2103551.4, filed 29 January, 2021, and 15 March, 2021 respectively. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copies of papers required by 37 CFR 1.55 have been filed in this application on 28 July, 2023.
The earliest possible priority for the instant application is 29 January, 2021.
Drawings
The objection to the drawings is withdrawn and the new drawings submitted on 03 August 2026 are accepted by the Examiner.
Specification
The objection to the disclosure is withdrawn in view of Applicant’s submission of replacement drawings.
Claim Interpretation
Claims 183-184 recite “optionally” numerous times throughout the claims. These claims are being interpreted consistent with their broadest reasonable interpretation as not requiring any of the claim limitations recited after each recitation of “optionally”.
Withdrawn Rejections/Objections in view of Applicant’s Amendments/Arguments
Claim Rejections - 35 USC § 112
The rejection of claims 183, and 185 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends is withdrawn in view of Applicant’s amendments to the claims. Applicant has amended claim 182 to read on a nucleic acid more generally and not specifically a single-stranded nucleic acid.
Maintained Rejections/Objections in view of Applicant’s Amendments/Arguments
Claim Rejections - 35 USC § 112
Claims 185-186 remain rejected and claims 184, 189, and 191 are newly 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 as necessitated by Applicant’s amendments to the claims. Applicant has amended the claims to remove all previously raised issues of indefiniteness with the exception of the rejection of claim 185. Applicant has also raised new issues of indefiniteness with their amendments.
Claim 185 remains rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential elements, such omission amounting to a gap between the elements. See MPEP § 2172.01. The omitted elements are: those responsible for enabling the nucleic acid to have the ability to express the transgene in a target cell. The omission of such elements is indefinite here because it is unclear how a nucleic acid itself “can express the transgene in a target cell” considering the fact that a nucleic acid at least needs a promoter, and that expression typically involves specific proteins and cell machinery. Therefore, it is unclear if the recitation “can express” is a positive limitation or only requires the ability to express.
Claim 186 still recites “and/or” in the nineteenth line of the claim. It is unclear whether Applicant intends the scope of claim 186 to encompass peptide motifs comprising either a polar side chain or an acidic or basic side chain or instead to encompass peptide motifs which have both a polar side chain and an acidic or basic side chain. Accordingly, a person having ordinary skill in the art would not be apprised of the scope of the patent protection sought.
Claim 185 recites the limitation "the single-stranded nucleic acid" in the first and second lines of the claim. There is insufficient antecedent basis for this limitation in the claim. Amended claim 182 now recites “a nucleic acid” rendering “the single-stranded nucleic acid” in claim 185 without proper antecedent basis.
Claim 184 recites the limitation "the single-stranded nucleic acid" in the first and second lines of the claim. There is insufficient antecedent basis for this limitation in the claim. Amended claim 182 now recites “a nucleic acid” rendering “the single-stranded nucleic acid” in claim 184 without proper antecedent basis.
Claim 189 recites the limitation "the single-stranded nucleic acid" in the first and second lines of the claim. There is insufficient antecedent basis for this limitation in the claim. Amended claim 182 now recites “a nucleic acid” rendering “the single-stranded nucleic acid” in claim 185 from which claim 189 depends and in claim 189 without proper antecedent basis.
Claim 191 recites the limitation "the single-stranded nucleic acid" in the first line of the claim. There is insufficient antecedent basis for this limitation in the claim. Amended claim 182 now recites “a nucleic acid” rendering “the single-stranded nucleic acid” in claim 185 from which claim 191 depends and in claim 191 without proper antecedent basis.
Response to Arguments
Applicant argues against the indefiniteness of claim 185 by arguing that no promoter is required where the nucleic acid is mRNA. The Examiner concedes this point. However, this does little to resolve the issue with claim 185 because where the nucleic acid is mRNA there are still necessary elements missing for the functional activity of “can express the transgene in a target cell”. For example, mRNA typically needs a 5’cap, a start codon, a stop codon, and some length of a poly-A tail to enable the mRNA to be translated into protein. Even still, the claim reads on a nucleic acid somehow expressing itself when “expression typically involves specific proteins and cell machinery”. Thus, the metes and bounds of claim 185 remain unclear and Applicant’s arguments are not found to be persuasive.
Claim Rejections - 35 USC § 103
Claims 183-185, and 187 remain rejected and new claims 188-191 and 195 are newly rejected under 35 U.S.C. 103 as being unpatentable over Kwok, et al., Acs Nano 7.5 (2013): 4668-4682. Hereinafter “Kwok” (Of Record) as evidenced by Promega (https://www.promega.com/products/vectors/protein-expression-vectors/pci-mammalian-expression-vector/?catNum=E1731, Accessed: 08 January, 2026) in view of Samaridou, et al. (Advanced drug delivery reviews 154 (2020): 37-63, hereinafter “Samaridou”), Mignani, et al. (Drug Discovery Today 25.6 (2020): 1065-1073, hereinafter “Mignani”), Abes, et al. Biochemical Society Transactions 35.4 (2007): 775-779, hereinafter “Abes”, US20130085139, hereinafter “Dickson”, Gan, et al. Nature communications 10.1 (2019): 871, hereinafter “Gan”, and Kuhn et al., Bioconjugate Chem. 18 March 2020; 31 (3): 729–742, hereinafter “Kuhn”. This rejection has been modified as necessitated by Applicant’s amendments to the claims.
Specifically, claims 182 and 186 now read on the composition of Kwok and have been rejected under 35 U.S.C. 102 below. Claims 183-185, and 187 remain rejected with new claims 188-191 and 195 being newly rejected with the addition of the Abes, Dickson, Gan, and Kuhn references.
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Regrading claims 183-184, Kwok teaches a composition comprising a peptide dendrimer, a nucleic acid, and a lipid (Kwok, Abstract). The peptide dendrimer of Kwok has a core peptide with lysine as a branching amino acid and two first peptide motifs (Kwok, Figure 1, See left). Kwok teaches transfection of HeLa cells with DNA complexes with or without the addition of a lipid component (DOTMA/DOPE) and a luciferase-expressing plasmid (pCI-Luc) (page 4671, legend Fig.2) . Thus, Kwok teaches the pCl-Luc plasmid as the DNA being transfected (Kwok, page 4678, third paragraph), where transfection with lipid/dendrimer/DNA complexes enhances transfection relative to dendrimer/DNA complexes alone (page 4670; col 2). A person having ordinary skill in the art understands the pCl-Luc plasmid to be at least 30 nucleotides as evidenced by Promega (see plasmid map). Thus, a person having ordinary skill in the art understands the composition of Kwok to be able to contain nucleic acids well above 30 nucleotides.
Kwok does not teach RNA or a single-stranded nucleic acid as the nucleic acid.
Thus, the prior art (Kwok) contained a composition which differs from the claimed composition by the substitution of a single stranded nucleic acid for the pCl-Luc plasmid of Kwok.
The level of ordinary skill in the art of lipid nanoparticle delivery of nucleic acids encompasses packaging nucleic acids of various types into lipid nanoparticles, including mRNA and siRNA (Samaridou, pages 48-54, “5.1.” and “5.2.” headings). In addition, Mignani teaches therapeutic aptamers of 40-100 nucleotides in length which are single stranded RNA or DNA that can specifically carry therapeutic oligonucleotides and be combined with dendrimers for precision therapies (Mignani, Abstract; page 1065, first paragraph; page 1067, last partial paragraph; page 1066, last full paragraph). Thus, a person having ordinary skill in the art would have understood from the teachings of Samaridou and Mignani that therapeutic nucleic acids of various kinds were able to be delivered via lipid/dendrimer/DNA complexes and that the interactions of said single stranded RNA or DNA with dendrimers were well known in the art.
Kwok teaches that compositions like the ones disclosed are efficient and useful reagents for transfection of mammalian cells (Kwok, “Conclusions”) and that their compositions improve transfection 6-10-fold over commercial reagents (Kwok, Abstract). A person having ordinary skill in the art understands that the pCl-Luc plasmid is a reporter plasmid (Kwok, page 4672, first full paragraph). Thus, a person having ordinary skill in the art could have substituted an aptamer carrying a therapeutic oligonucleotide as taught by Mignani or an mRNA as taught by Samaridou for the reporter plasmid in the lipid/dendrimer/DNA complexes compositions of Kwok and the results of that substitution would have been predictable insofar as the peptide dendrimer composition would still function to deliver a payload at a transfection efficiency 6-10-fold higher than commercial reagents, and the aptamer carrying a therapeutic oligonucleotide or the mRNA would continue to possess their respective functions. The substitution of a single stranded nucleic acid as taught by Mignani and Samaridou for the reporter plasmid of Kwok in the composition of Kwok is no more than the simple substitution of one known element for another to produce predictable results. Accordingly, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have substituted an RNA or a ssDNA according to Mignani and Samaridou for the plasmid of Kwok and to have arrived at the invention claimed in instant claims 183-184 with predictable results.
Regarding claim 185, one of the mRNAs taught by Samaridou to be deliverable via lipid nanoparticle is an mRNA encoding influenza H1 hemagglutinin antigen (a transgene) which functions as a vaccine and is, thus, expressed in target cells (Samaridou, page 48, fifth paragraph).
Regarding claims 187 and 195, neither Kwok, Samaridou, nor Mignani disclose including a cell penetrating peptide in the composition or the specific cell penetrating peptide of SEQ ID NO: 2.
However, Abes teaches cell-penetrating-peptide-based delivery of oligonucleotides (Abes, Title). Abes specifically teaches that CPPs have been used widely for intracellular delivery of drugs, biomolecules, and particles and teaches a new arginine rich CPP for efficient intracellular delivery (Abes, Abstract). The Abes reference is cited by Dickson who teaches therapeutic oligomers (Dickson, Abstract). Dickson specifically teaches to conjugate a dendrimer to a cell penetrating peptide wherein the cell penetrating peptide is a sequence having 100% identity to instant SEQ ID NO: 2 where X is 6-aminohexanoic acid and A is β-alanine (See screenshot below and [0018]).
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Dickson also teaches the successful delivery of nucleic acids with dendrimers conjugated to the cell penetrating peptide (Dickson, [0035]-[0039]). Thus, a person having ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to conjugate the CPP of Dickson/Abes to the dendrimer of Kwok to improve the intracellular delivery of the nucleic acids. They would have reasonably expected success in adding the CPP of Dickson/Abes to the dendrimer complexes of Kwok insofar as Dickson teaches that the CPP can be conjugated to dendrimers and still possess its functional properties.
Regarding claim 188, Samaridou teaches mRNA.
Regarding claim 189, neither Kwok, Samaridou, nor Mignani disclose the delivery of a single-stranded nucleic acid which can modulate expression or activity of an endogenous gene via exogenous expression of further copies of the endogenous gene.
However, Gan teaches mRNA molecules encoding VEGF-A injected into patients with type II diabetes (Gan, Title, Abstract). VEGF-A is an endogenous gene. The claimed composition differed from the composition of Kwok, Mignani, and Samaridou only in the use of a VEGF-A encoding mRNA specifically. The substitution of an mRNA encoding VEGF-A as taught by Gan for the reporter plasmid of Kwok in the composition of Kwok is no more than the simple substitution of one known element for another to produce predictable results. Accordingly, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have substituted an mRNA encoding VEGF-A as taught by Gan for the plasmid of Kwok and to have arrived at the invention claimed in instant claim 189 with predictable results.
Regarding claim 190, Samaridou teaches vaccines which deliver antigens.
Regarding claim 191, neither Kwok, Samaridou, nor Mignani disclose the delivery of a single-stranded nucleic acid encoding one or more components of a CRISPR/Cas system.
However, Kuhn teaches Cas9/sgRNA ribonucleoprotein complexes delivered via sequence-defined oligo amides (OAAs) (Kuhn, Abstract). Kuhn teaches the delivery of these ribonucleoprotein complexes in this way as the mere packaging of the complexes in OAAs as opposed to other forms of delivery and teaches that Cas9/sgRNA ribonucleoprotein complexes can be efficiently delivered in this way (Kuhn, Abstract, pages 729-730, last partial and first partial paragraphs respectively). sgRNAs are single-stranded nucleic acids which encode in themselves a component of the CRISPR/Cas system. The substitution of a single stranded nucleic acid as taught by Kuhn for the reporter plasmid of Kwok in the composition of Kwok is no more than the simple substitution of one known element for another to produce predictable results. Accordingly, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have substituted an sgRNA as taught by Kuhn for the plasmid of Kwok and to have arrived at the invention claimed in instant claim 191 with predictable results.
Response to Arguments
Applicant argues (1) that the above obviousness rationale “significantly oversimplifies both the technical challenges associated with nucleic acid delivery and the technical contribution demonstrated by the present application,” (Remarks, page 12) (2) that the claimed compositions provide efficient and functional delivery of nucleic acids (Remarks, page 12), (3) that Kwok only evidences in vitro results (Remarks, page 13), and (4) the rejection is based upon hindsight reasoning (Remarks, page 15). These arguments have been fully considered but have not been found persuasive for the following reasons.
At the outset and in response to applicant's arguments against the references individually, it is noted that one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Applicant has argued against Kwok and against Mignani and Samaridou in their individual capacities without addressing the combination of these references.
(1) Applicant argues “this characterisation significantly oversimplifies both the technical challenges associated with nucleic acid delivery and the technical contribution demonstrated by the present application. The present invention is not directed to the identification of new nucleic acid cargo that may be incorporated into a known carrier system. Rather, the application demonstrates that peptide dendrimer/lipid formulations are capable of effectively packaging, protecting, delivering, and functionally expressing nucleic acids in vivo following systemic administration. The achievement of functional extrahepatic delivery represents a particularly significant technical advance given the well-recognised difficulties associated with delivering nucleic acids outside the liver,” (Remarks, page 12).
This argument has been fully considered but has not been found persuasive because Applicant is not claiming an in vivo method of use. Applicant specifically elected the composition for examination on the merits. Precisely because of this election, the claims under examination are decidedly simpler than an in vivo method insofar as where claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). Thus, for the purpose of applying prior art, a disclosure of an identical or substantially identical product is presumed to inherently possess claimed properties. See MPEP 2112.01. Here, Applicant argues for properties not claimed but even were these properties to be claimed in as properties of the composition, the same rejection would apply because an identical or at least substantially identical product is disclosed in the prior art. It is further noted that Applicant’s amendments brought the claimed composition in claim 182 within the reaches of 35 U.S.C. 102 in view of the Kwok disclosure. It is unclear how the composition of Kwok (which is identical to the composition instantly claimed) would not possess the properties that Applicant here touts. Accordingly, this argument has been fully considered but has not been found persuasive.
(2)/(3) Applicant argues
The application as filed contains extensive experimental evidence demonstrating that the claimed compositions provide efficient and functional delivery of nucleic acids, including plasmid DNA (see, e.g., Figures 6 and 8) and mRNA (see, e.g., Figures 10 to 17) to a broad range of tissues. Notably, the data are not limited to observations of tissue accumulation or biodistribution. Rather, the experiments demonstrate functional expression and biological activity of the delivered nucleic acid payloads. This distinction is important because accumulation of a labelled carrier or nucleic acid within a tissue does not establish successful intracellular delivery, endosomal escape, release of cargo, or subsequent biological activity. In particular, Figures 10 to 17 demonstrate that peptide dendrimer/lipid/mRNA formulations are capable of mediating luciferase expression in numerous extrahepatic tissues, including lung, spleen, lymph nodes, gastrocnemius muscle, heart, kidney, adipose tissue, and brain. Moreover, the inventors surprisingly found that, following intravenous administration to mice of peptide dendrimer/lipid/DNA formulations comprising DNA encoding either follistatin (Figure 6) or luciferase (Figure 8), expression of the encoded peptide was abundant in skeletal muscle. The above results establish that the claimed compositions are capable of overcoming barriers that have historically limited the broader application of lipid-based nucleic acid delivery systems. As acknowledged in the application itself, preferential accumulation and expression in the liver is a common characteristic of lipid nanoparticles generally, and achieving efficient extrahepatic delivery has long been recognised as a significant challenge in the field. The present inventors have demonstrated a delivery platform capable of addressing this particular challenge. The application provides further evidence supporting the robustness of the claimed delivery system through studies directed to immune-cell targeting. Figures 21-24 employ fluorescently labelled mRNA to demonstrate delivery to immune-cell populations within the spleen, bone marrow, blood, and lymph nodes. The specification expressly states that delivery of mRNA to a wide range of immune cells within the spleen can be achieved using NTX1 and G1,2-RL,3-LR dendrimer compositions. These data provide additional evidence that the claimed compositions are not merely capable of transporting nucleic acids to tissues, but are capable of mediating delivery to biologically relevant cell populations that are particularly difficult to transfect in vivo. Accordingly, the application provides extensive experimental support demonstrating that the claimed peptide dendrimer/lipid formulations constitute a general platform for the functional delivery of nucleic acids to extrahepatic tissues and diverse cell populations. The technical contribution of the invention therefore lies not in the identity of the nucleic acid cargo, but in the discovery that the peptide dendrimer/lipid/nucleic acid systems can successfully deliver nucleic acids in vivo while achieving therapeutically relevant biological effects. In addition, the present application demonstrates an absence of detectable liver toxicity, for example in Figures 26 and 27, for mRNA and DNA cargos, respectively. In contrast, Kwok provides no teaching that would have led a skilled person to reasonably expect such results. (Remarks, pages 12-13).
This argument has been fully considered but has not been found persuasive for the following reasons. Firstly, to the extent this argument is an attempted argument for unexpected results, it is countered that evidence of unexpected properties may be in the form of a direct or indirect comparison of the claimed invention with the closest prior art which is commensurate in scope with the claims. See In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980) and MPEP § 716.02(d) - § 716.02(e). An affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979). “A comparison of the claimed invention with the disclosure of each cited reference to determine the number of claim limitations in common with each reference, bearing in mind the relative importance of particular limitations, will usually yield the closest single prior art reference.” In re Merchant, 575 F.2d 865, 868, 197 USPQ 785, 787 (CCPA 1978) (emphasis in original). Where the comparison is not identical with the reference disclosure, deviations therefrom should be explained, In re Finley, 174 F.2d 130, 81 USPQ 383 (CCPA 1949), and if not explained should be noted and evaluated, and if significant, explanation should be required. In re Armstrong, 280 F.2d 132, 126 USPQ 281 (CCPA 1960) (deviations from example were inconsequential). See also MPEP 716.02e. Here, no attempt was made to compare the results of the present application directly or indirectly with the results of Kwok. Applicant’s arguments appear to assert that in vitro data is not enough to reasonably expect similar activity for the composition of Kwok in vivo without providing any support for such a claim. In vitro data are typically the first order of investigation before in vivo experiments are performed in the process of developing therapeutics so an argument that runs counter to this notion must have some basis in evidence for it to be persuasive. In fact, the amended claims actually read precisely on the composition of Kwok which is why a new 35 U.S.C. 102 rejection has been made in response. In addition, Applicant is reminded that the claims do not require the in vivo functional activity herein argued and even were they to require it, they would still be anticipated/obvious over Kwok because the claims are directed to a composition and the patentability of the composition is measured by the composition itself not by any inherent properties that would be reasonably expected from the same composition present in the prior art. Accordingly, this argument has been fully considered but has not been found persuasive.
(4) Applicant argues “the Examiner's conclusion can only be reached through hindsight. The cited references do not teach, suggest or provide a reasonable expectation that the peptide dendrimer/lipid systems of Kwok would achieve the functional delivery outcomes demonstrated in the present application, including efficient in vivo delivery and activity in extrahepatic tissues and relevant cell populations, whilst not inducing any toxic side effects. Applicant's experimental results therefore cannot be dismissed as the predictable consequence of a routine experimentation. Instead, they demonstrate that the claimed compositions possess properties and capabilities that are not taught or suggested by the cited art and would not have been reasonably expected by the skilled person,” (Remarks, page 15).
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Here, Kwok discloses the instant composition (hence the 35 U.S.C. 102 rejection below) with the only differences between the composition of Kwok and the instant claims being the nucleic acid cargo within. Applicant does not argue that the composition cannot comprise any nucleic acid because to do so would certainly run counter to the prior art which teaches an identical composition (Kwok) carrying a relatively massive nucleic acid payload (pCl plasmid). Thus, it is unclear how any hindsight can even be implied here beyond that which is already necessary to the construction of the obviousness rejection itself. Mignani and Samaridou teach different nucleic acid payloads that can be encapsulated within other dendrimer/nanoparticulate technologies. The level of ordinary skill in the art of lipid nanoparticle delivery of nucleic acids encompasses packaging nucleic acids of various types into lipid nanoparticles as evidenced by Samaridou. Thus, it would have been obvious to package any nucleic acid molecule within the composition of Kwok for delivery of the nucleic acid molecule according to Kwok and the results of doing so would have been predictable insofar as a person having ordinary skill in the art would have reasonably expected to obtain similar properties to those taught in Kwok. Those properties need not be the precise in vivo efficacy that Applicant argues here (1) because they are not claimed, and (2) because they would be presumed if they were claimed because the composition of Kwok is identical to the composition claimed. Accordingly, this argument has been fully considered but has not been found persuasive.
Double Patenting
Claims 182-187 remain provisionally rejected and new claims 188-196 are newly provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-5, 8-10, 12-13, 17, 19, 25-26, 32-37, and 42 of copending Application No. 19,100,421 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant invention is an obvious variant of the reference invention.
Reference claim 1 recites: “A nanoparticle comprising a peptide dendrimer, a nucleic acid, and a lipid, wherein the peptide dendrimer comprises at least: a core peptide sequence, a first branching residue and two first peptide motifs, wherein the lipid:nucleic acid weight/weight ratio of the nanoparticle is at least 2:1 and/or the nanoparticle is a coated nanoparticle comprising a peptide at its surface, wherein the nanoparticle can target a target cell or tissue, e.g. a myeloid, lymphoid, muscle, lung cell, a CD206+ cell and/or tumour cell, and/or myeloid, lymphoid, muscle, lung tissue and/or tumour tissue, and wherein the nanoparticle is capable of transfecting the target cell in vitro at an efficiency of at least 10%.”
Instant claim 182 recites: “A composition comprising a peptide dendrimer, a nucleic acid and a lipid, wherein the peptide dendrimer comprises at least: a core peptide sequence, a first branching residue and two first peptide motifs wherein the branching residue is lysine, 2,4-diaminobutyric acid, ornithine, or diaminopropionic acid; wherein the nucleic acid comprises a nucleic acid of at least 30, at least 35, at least 40, at least 45, or at least 50 nucleotides.”
The reference claims are both broader and narrower than the instant claims. With respect to the ways in which the reference claims are narrower, they are considered a species of the invention instantly claimed. It is well established that a species of a claimed invention renders the genus obvious. In re Schaumann , 572 F.2d 312, 197 USPQ 5 (CCPA 1978). With respect to the reference claims reciting only “nucleic acid” which is broader than the “single-stranded nucleic acid of at least 30 nucleotides” instantly claimed, note that MPEP 804(II)(2)(a) sets forth instances where it is acceptable to utilize the disclosure of a U.S. patent document in conjunction with its claims for ODP rejections.
In particular, the MPEP notes that the portion of the specification that supports the patent claims may be considered. The court in AbbVie Inc. v. Kennedy Institute of Rheumatology Trust pointed out that “this use of the disclosure is not in contravention of the cases forbidding its use as prior art, nor is it applying the patent as a reference under 35 U.S.C. 103, since only the disclosure of the invention claimed in the patent may be examined.” In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014). The court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Pfizer, Inc. v. Teva Pharm. USA, Inc., 518 F.3d 1353, 86 USPQ2d 1001 (Fed. Cir. 2008); Geneva Pharmaceuticals Inc. v. GlaxoSmithKline PLC, 349 F3d 1373, 1385-86, 68 USPQ2d 1865, 1875 (Fed. Cir. 2003).
The specification of the reference patent discloses that the nucleic acid can be an eGFP mRNA and that mRNA is a single stranded nucleic acid (reference specification, page 48, lines 24-37; page 64, lines 18-20). eGFP mRNA is over 30 nucleotides long. Thus, the instant composition is an obvious variant of the reference nanoparticle.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant requests withdrawal of the double patenting rejection on the bare assertion that the inventions of the respective applications are distinct (Remarks, page 15). Applicant has provided no reasoning and no further detail as to their position that the inventions are distinct. Therefore, this argument has been fully considered but has not been found to be persuasive.
New Rejections Necessitated by Applicant’s Amendments to the claims
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 182, 186, 192-194, and 196 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kwok, et al., Acs Nano 7.5 (2013): 4668-4682. Hereinafter “Kwok” (Of Record) as evidenced by Promega (https://www.promega.com/products/vectors/protein-expression-vectors/pci-mammalian-expression-vector/?catNum=E1731, Accessed: 08 January, 2026). This rejection was necessitated by Applicant’s amendment to claim 182 to read on nucleic acids more generally and not to require single-stranded nucleic acids specifically.
Regarding claim 182, Kwok teaches a composition comprising a peptide dendrimer, a nucleic acid, and a lipid (Kwok, Abstract). The peptide dendrimer of Kwok has a core peptide with lysine as a branching amino acid and two first peptide motifs (Kwok, Figure 1, See left). Kwok teaches transfection of HeLa cells with DNA complexes with or without the addition of a lipid component (DOTMA/DOPE) and a luciferase-expressing plasmid (pCI-Luc) (page 4671, legend Fig.2). Thus, Kwok teaches the pCl-Luc plasmid as the DNA being transfected (Kwok, page 4678, third paragraph), where transfection with lipid/dendrimer/DNA complexes enhances transfection relative to dendrimer/DNA complexes alone (page 4670; col 2). The pCl-Luc plasmid is at least 30 nucleotides long as evidenced by Promega who teaches that pCl plasmid backbone is 4,006bp long (see plasmid map).
Regarding claim 186, Kwok teaches that the first peptide motifs can comprise leucine, lysine, alanine, histidine, or arginine (Kwok, Figure 1).
Regarding claim 192, Kwok teaches two second branching residues with four second peptide motifs comprised of the same amino acids as the first peptide motifs (Kwok, Figure 1).
Regarding claim 193, Kwok teaches four third branching residues with eight third peptide motifs comprised of the same amino acids as the first and second peptide motifs (Kwon, Figure 1).
Regarding claim 194, Kwok teaches the first and second peptide motifs consist of dipeptides comprising an arginine and a leucine (Kwok, Figure 1).
Regarding claim 196, Kwok teaches DOTMA/DOPE as the lipid component of the composition (Kwok, page 4671, legend Fig.2).
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRENDAN THOMAS TINSLEY whose telephone number is (703)756-5906. The examiner can normally be reached Mon-Fri 8:00-5:00.
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, MARIA G LEAVITT can be reached at 571-272-1085. 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.
/BRENDAN THOMAS TINSLEY/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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