DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This action is in response to the papers filed on 08/03/2026. Claims 1, 3-5, 7,10, 12, 15-17, 21, 35-41 are currently pending as per claims filed on 08/03/2026. Claims 27 and 29 corresponding to restricted Groups II and III, respectively have been cancelled by amendments filed 08/03/2026.
Applicant’s election of Group I, without traverse, of claims 1, 3-5, 7,10, 12, 15-17, 21, 35-41 in the reply filed on 07/17/2026 is acknowledged.
Moreover, applicants’ election of the following species without traverse is acknowledged:
Claim 4 prong (ii), which recites, inter alia, that the genetic element comprises the nucleic acid sequence of nucleotides 2463-2876 of SEQ ID NO: 1 or a complement thereof, or a nucleic acid sequence having at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto.
Claim 5 prong (i), which recites, inter alia, that the proteinaceous exterior comprises an ORFl molecule comprising the amino acid sequence of SEQ ID NO: 2,or an amino acid sequence having at least 75%, 80%, 85%, 90%, 95%, 96%, 97%,98%, or 99% sequence identity thereto.
Upon further reconsideration of the election of species requirement for claims 3, 4, 7, and 10 AND the species election within the claims (i-ii/iii for claims 3, 4, 5, 7, and 10) has been withdrawn by the examiner.
The requirement is still deemed proper and is therefore made FINAL.
Therefore, claims 1, 3-5, 7,10, 12, 15-17, 21, 35-41 are subject to examination to
which the following grounds of rejection are applicable. Claims 1, 17 and 21 are independent claims.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International
Application No. PCT/US2023/064434 filed 03/15/2023 which claims priority to US Provisional Application No. 63/320,515 filed 03/16/2022
Additionally, the application is a CIP of PCT/US2022/077923 filed 10/11/2022 which claims priority to US Provisional Application No. 63/320,515 filed 03/16/2022. Thus, the earliest possible priority for the instant application is 03/16/2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 05/27/2025 and
08/03/2026 were filed before the mailing date of the current office action. The
submission is in compliance with the provisions of 37 CFR 1.97.
Accordingly, the information disclosure statement is being considered by the
examiner.
Claim Objections
Claim 5 is objected to because abbreviations such as ORF1 and VP1 should be spelled out at the first encounter in the claims. Appropriate correction is required.
Claim 21 is objected to because abbreviations such as VEGF should be spelled out at the first encounter in the claims. 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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 4, 7, 10, and 12 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 4 recites the term “and/or” in line 21. It is unclear what the metes and bounds of this term, as “and” could be interpreted wherein the genetic element comprises the nucleic acid sequence of (i), or (i) and (ii), or, “or” would imply that the nucleic acid sequences are in the alternative. Appropriate correction is required.
Claim 7 recites the term “and/or” in line 15. It is unclear what the metes and bounds of this term, as “and” could be interpreted wherein the genetic element comprises the nucleic acid sequence of (i), or (i) and (ii), or, “or” would imply that the nucleic acid sequences are in the alternative. Appropriate correction is required.
Claim 10 recites the term “and/or” in line 23. It is unclear what the metes and bounds of this term, as “and” could be interpreted wherein the genetic element comprises the nucleic acid sequence of (i), or (i) and (ii), or, “or” would imply that the nucleic acid sequences are in the alternative. Appropriate correction is required.
Claim 12 recites the term “and/or” in line 8. It is unclear what the metes and bounds of this term, as “and” could be interpreted wherein the genetic element comprises the nucleic acid sequence of (i), or (i) or (iii), or (i) or (iii), or, “or” would imply that they are all in the alternative. Appropriate correction is required.
Claim Rejections - 35 USC § 112(a) - Scope of Enablement
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 3-5, 7,10, 12, 15-17, 21, 35-41 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for:
a method of delivering the exogenous effector to the posterior eye cup (PEC) or the retinal pigmented epithelium (RPE) of a mouse, the method comprising subretinal injection of a RING19-based anellovirus vector and chicken anemia virus (CAV)-based anellovirus
transduction in human RPE cells in vitro of a RING19-based anellovirus vector
the RING19-based anellovirus comprising a VP1 or ORF1 molecule of an anellovirus
does not reasonably provide enablement for a method of delivering a genus of exogenous effectors to the PEC or RPE and genus of proteinaceous encapsulating elements to a subject by using any route of administration to target the PEC or the RPE using a genus of anelloviridae family vectors. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
In relation to claims 3, 4, 5, 7, and 10, which recite wherein the genetic element comprises specific nucleic acid sequences from SEQ ID NO: 1, 54, and 5 (claims 3, 4, 7 and 10) and wherein the proteinaceous exterior comprises an amino acid sequence of SEQ ID NO: 2, 58, or 251 (claim 5), the claims additionally recite, in the alternative, the genetic element/proteinaceous exterior can have at least 75-99% identity to the respective sequence. However, the specification is only enabling for 100% sequence identity to:
nucleotides 1-71 of SEQ ID NO: 1 (RING19) (Table N1.1)
nucleotides 323-393 of SEQ ID NO: 54 (RING2) (Table N2)
nucleotides 1-374 of SEQ ID NO: 5 (CAV) (Table N3)
nucleotides 1-100 of SEQ ID NO: 1 (RING19) (Table N1.1)
nucleotides 2463-2876 of SEQ ID NO: 1 (RING19) (Table N1.1)
amino acid sequence of SEQ ID NO: 2 (RING 19 ORF1) (Table A1)
amino acid sequence of SEQ ID NO: 58 (RING 2 ORF1) (Table A2)
amino acid sequence of SEQ ID NO: 251 (CAV VP1) (Table A3)
Thus, the specification does not enable for genetic elements and proteinaceous elements with a range of 75-99% identity to the corresponding range of nucleotides or amino acid sequences as recited in the claims.
breadth of the claim; nature of the invention
Claim 1 is broad, encompassing a method of delivering any exogenous effector to the PEC or the RPE of any subject, the method comprising administering, in any route of administration, any anelloviridae family vector. Furthermore, the claim recites the vector can comprise any genetic element which comprises a nucleic acid to encode the exogenous effector and comprises any proteinaceous exterior. Thus, the claims are drawn to a large genus of exogenous effectors, proteinaceous exterior, and Anelloviridae vectors, which can be administered to a variety of subjects using various routes of administration. Claim 3, 4, 7, and 10 further limits the genetic element of claim 1 to specific sequences set forth in SEQ ID NO: 1, 5, and 54 and claim 5 further limits the proteinaceous exterior to specific sequences set forth in SEQ ID NO: 2, 58, and 251. Claim 15 and 16 further limit the subject in claim 1 to a subject having macular degeneration and a retinal disease or a VEGF-associated disorder. Claim 17 is an independent claim and recites the method comprises subretinal or intravitreal administration of an Anelloviridae. Claim 21 is an independent claim reciting a method of treating a disease or disorder selected from a group, the method comprising administering an Anelloviridae family vector to a subject.
the amount of direction provided by the inventor; the existence of working examples:
However, the specification does not disclose a reduction to practice in the method of delivering any exogenous effector to the PEC or RPE by any route of administration and using any Anelloviridae family vector comprising any proteinaceous exterior. The specification recites a method comprising subretinally injecting a CAV vector comprising a luciferase payload (CAV-luc) genetic element in a mouse showing vector expression in the PEC which contains the RPE (example 23, para 1220), subretinally injecting a RING19-eGFP Anellovector in a mouse showing vector expression in the PEC (example 26, para 1235), and transducing human MOLT-4 cells with a RING19-eGFP Anellovector using in vitro cell culture (example 27, para 1264). Furthermore, the specification discloses testing two concentrations (high dose: 1.2 e+11; low dose: 1.2 e+10 vg/ml) when subretinally injected into the eyes of mice (Table AA4, Example 28) and that the proteinaceous exterior is an ORF1 of the RING19 and RING2 vector as set forth in SEQ ID NO: 2 and 58 and the VP1 of CAV as set forth in SEQ ID NO: 251. The specification provides no examples of treating any disease or disorder in any subject using any of the disclosed vectors.
Thus, the specification does not provide sufficient teachings for the enablement of using any Anelloviridae family vector, other than CAV and RING19 and RING2. The specification also does not disclose that the CAV and RING19 and RING2 vector can be administered to the PEC or RPE of any subject by any means of administration, except in vivo RPE transduction for human RPE cells (for RING19 vector) and subretinal injection in mice (for CAV and RING19) and the exogenous effector being eGFP. Furthermore, the specification lacks any examples of treating any disease or disorder, let alone any recited in the claim 21.
the state of the prior art; the level of predictability in the art:
The use of Anelloviridae family vectors as a gene therapy vehicle remains in infancy stage of development. While Anelloviridae family vectors have demonstrated promise as a viral vector to efficiently deliver therapeutics for ocular diseases, the state of the prior indicates high degree of unpredictability.
There are limited studies investigating the ability of Anelloviridae family vectors to be administered to the PEC or the RPE of a subject such that it can deliver exogenous effectors to the PEC or the RPE. Nawandar et al (bioRxiv, 2022, pages 1-32) used an anellovirus derived from human retinal pigmental epithelium (nrVL4619), subsequently in vitro produced in a cell line, and show infectivity when subretinally or intravitreally injected into a mouse eye (page 14-15, Subretinal Injection and Intravitreal Injection; Figure 8A-B). Similarly, Prince et al (Molecular Therapy: Methods & Clinical Development, 2025, pages 1-17) corroborates the finding that anellovectors of nrVL4619 can transduce human RPE cells during in vitro culture (page 6, left col, para 2) and can successfully infect the PEC (which is composed of RPE cells) and express eGFP payload when subretinally administered in a mouse ocular model (page 6, right col, para 3). While not necessarily related to administration to the PEC or the RPE, Prince further demonstrated that if one wished to transduce cells of the central nervous system, the anellovector can be intracerebroventricular (ICV) injected through the left and right lateral ventricles in the brain in a mouse model (page 8, right col, para 2), further indicating that a more localized injection is required to transduce cells of interest. Importantly, these studies do not demonstrate any treatment of any disease or disorder, but rather only suggest that the anellovirus vector hold potential in use as a vehicle for therapeutic delivery. Similarly, the state of prior art indicates that further investigation of Anellovector-mediated transgene expression is even well tolerated by a host (Prince, page 11, left col, para 2).
Collectively, the prior art does not indicate that administration of any anellovirus vector by any means of administration would predictability be delivered to the PEC or the RPE of any subject. Rather, the prior art of Nawandar and Prince are, to the Examiner’s knowledge, are the only studies describing using an anellovirus vector to deliver an exogenous effector to the PEC or the RPE and wherein the delivery is achieved via subretinal or intravitreal injection or through transduction by in vitro culture. Moreover, the use of anellovirus as vectors remains at a proof-of-concept stage, signifying treatment of any disease or disorder has yet to be shown.
the quantity of experimentation needed to make or use the invention based on the content of the disclosure:
The skilled artisan would be required to perform under levels of experimentation in order to practice the claimed invention. While the instant application discloses a method of delivering a eGFP -CAV and -RING19 anellovirus vector to a mouse PEC or RPE via intravitreal or subretinal injection or transducing in vitro human RPE cells with RING19 vector, there is not enough information in the prior art indicating the feasibility and predictable outcomes regarding delivering any exogenous effector to the PEC or the RPE of any subject using an anelloviridae family vector and with any method of administration such that the method could treat the array of disorders recited in claim 21.
Thus, the skilled artisan would be forced to identify 1) the type of anellovirus required which can be administered to the PEC or the RPE of the subject, 2) what percent identity of the nucleic acid sequence is required for the genetic element, 3) the route of administration necessary to deliver the exogenous effector using the Anelloviridae family vector to the PEC or the RPE of the subject, 4) the proteinaceous element that can be used, including the percent identity to the SEQ ID NO required, to encapsulate the genetic element and 5) determine if the method can sufficiently treat the disease or disorder upon administration of the Anelloviridae family vector.
Conclusion
When all of the Wands factors are considered together, they establish a prima facie case that the specification is not enabling for the claims. The specification and state of the prior art only provide details pertaining to a method of delivering eGFP to the PEC or the RPE of a mouse subject, of in vitro cultured human RPE cells, the method comprising administering a RING19 or RING2 or CAV-based Anellovirus which is subretinally or intravitreally administered to the mouse eye or transduced in cell culture for human cells. Moreover, the specification only discloses that 100% sequence identity for the nucleic acid sequence and the amino acid sequences to the corresponding SEQ ID NOs recited in claims 3, 4, 5, 7 and 10.
While a lack of a working embodiment showing relevant data to support the methods cannot be a sole factor in determining enablement, the lack of any working examples, in light of the unpredictable nature of the art and the minimal direction applicants present, provides additional weight to the scope of enablement in consideration of the Wands factors as a whole. Thus, one of ordinary skill in the art would not have had a reasonable expectation of success in making or using the claimed invention beyond the scope of the disclosure and current state of the art.
Written Description
Claims 1, 3-5, 7,10, 12, 15-17, 21, 35-41 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The Federal Circuit has clarified the written description requirement. The court stated that a written description of an invention "requires a precise definition, such as by structure, formula, [or] chemical name, of the claimed subject matter sufficient to distinguish it from other materials". University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568; 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). The court also concluded that "naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not description of that material". Id. Further, the courtheld that to adequately describe a claimed genus, Patent Owner must describe a representative number of the species of the claimed genus, and that one of skill in the art should be able to "visualize or recognize the identity of the members of the genus".
The claims are drawn to a method of delivering an exogenous effector to the PE or RPE of a subject, the method comprising administering to the PEC or the RPE of a subject an Anelloviridae family vector comprising (i) a genetic element comprising a nucleic acid sequence encoding an exogenous effector; and (ii) a proteinaceous exterior encapsulating the genetic element. Furthermore, claims 3, 4, 5, 7, and 10, which depend on claim 1, recite recite wherein the genetic element comprises specific nucleic acid sequences from SEQ ID NO: 1, 54, and 5 (claims 3, 4, 7 and 10) and wherein the proteinaceous exterior comprises an amino acid sequence of SEQ ID NO: 2, 58, or 251 (claim 5), the claims additionally recite, in the alternative, the genetic element/proteinaceous exterior can have at least 75-99% identity to the respective sequence.
With the exception of anellovirus vectors RING19, RING2, and CAV which comprise 100% sequence identity to the following nucleotide ranges and SEQ ID NOs:,
GENETIC ELEMENT
nucleotides 1-71 of SEQ ID NO: 1 (RING19) (Table N1.1)
nucleotides 323-393 of SEQ ID NO: 54 (RING2) (Table N2)
nucleotides 1-374 of SEQ ID NO: 5 (CAV) (Table N3)
nucleotides 1-100 of SEQ ID NO: 1 (RING19) (Table N1.1)
nucleotides 2463-2876 of SEQ ID NO: 1 (RING19) (Table N1.1)
PROTEINACOUS ELEMENT
amino acid sequence of SEQ ID NO: 2 (RING 19 ORF1) (Table A1)
amino acid sequence of SEQ ID NO: 58 (RING 2 ORF1) (Table A2)
amino acid sequence of SEQ ID NO: 251 (CAV VP1) (Table A3)
the Applicant’s do not describe a representative number of species of the broadly claimed anellovirdae family vector comprising genetic element comprising any nucleic acid sequence and any proteinaceous exterior encapsulating the genetic element. Furthermore, the Applicant does not describe representative examples of the nucleic acid sequence of nucleotides of the claims ranges (as recited in claim 3, 4, 7, and 10 for genetic element) and the amino acid sequence (as recited in claim 5) being any less than 100% identical (at least 75%, 70%, 85%, etc). Rather, the specification only provides examples of using RING19, RING2, and CAV in the following manner:
GENETIC ELEMENT
nucleotides 1-71 of SEQ ID NO: 1 (RING19) (Table N1.1)
nucleotides 323-393 of SEQ ID NO: 54 (RING2) (Table N2)
nucleotides 1-374 of SEQ ID NO: 5 (CAV) (Table N3)
nucleotides 1-100 of SEQ ID NO: 1 (RING19) (Table N1.1)
nucleotides 2463-2876 of SEQ ID NO: 1 (RING19) (Table N1.1)
PROTEINACOUS ELEMENT
amino acid sequence of SEQ ID NO: 2 (RING 19 ORF1) (Table A1)
amino acid sequence of SEQ ID NO: 58 (RING 2 ORF1) (Table A2)
amino acid sequence of SEQ ID NO: 251 (CAV VP1) (Table A3)
With the exception of RING19, RING2, and CAV anellovirus vector with 100% sequence match to the respective genetic element nucleic acid sequence (and ranges) and proteinaceous exterior amino acid sequence as recited above, Applicants have not described any other anelloviridae vector with a genetic element and a proteinaceous exterior that is less than 100% identical to the respective sequence, let alone the genetic element and proteinaceous element being of any origin, such that the vector can confer the phenotype of being appropriately delivered to the PEC or the RPE of a subject with a contemplated use of treating a disease or disorder of the eye as disclosed in the specification (para 1021-1035). Applicants fail to specifically describe any other possible anelloviridae vector, genetic element, or proteinaceous exterior from the broadly claimed genus, including any with at least 75-99% identity to their respective sequence.
This disclosure is not deemed to be descriptive of the complete structure of a representative number of species encompassed by the claims as one of skill in the art cannot envision all the genetic elements and proteinaceous exteriors in any anelloviridae family vector such that the vector can be administered to the PEC or the RPE of a subject based on the teachings in the specification. The specification does not teach regions or domains of the genetic element and proteinaceous exterior that are essential for the claimed activity.
As discussed in MPEP 2163(I)(A), “a biomolecule sequence described only by a functional characteristic, without any known or disclosed correlation between that function and the structure of the sequence, normally is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence”
Moroever, the instant Specification fails to provide guidance for which nucleotides of SEQ ID NO: 1, 54, and 5 can be substituted, and to which nucleotides must not be changed, to maintain the functional activity of the encoded genetic element. This failed guidance is similarly applicable to the modifications claimed to the amino acid sequences set forth in SEQ ID NO: 2, 58, and 251. Focusing on the nucleic acid sequences, the Specification fails to provide guidance for which nucleotides (and similarly, amino acids for claim 5) can be deleted and which regions of the genetic element (and proteinaceous element for claim 5) can tolerate insertions and/or additions and still produce a functional protein. Describing and reducing to practice the claimed genus of nucleotide substitutions/deletions/insertions in the gene of SEQ ID NO: 1, 54, and 5 is unpredictable. While it is known that many nucleotide substitutions, additions or deletions are generally possible in any given gene, the positions within the gene’s sequence where the resulting amino acid changes can be made with a reasonable expectation of success (without altering protein function) are limited. Certain positions in the sequence are critical to the protein’s structure/function. (see Ngo, in The Protein Folding Problem and Tertiary Structure Prediction, Merz et al. (eds.), Birkhauser Boston: Boston, MA, pp. 433 and 492-495, 1994). Rudinger (in Peptide Hormones, Parsons (ed.), University Park Press: Baltimore, MD, pp. 1-7, 1976) discloses that even for peptide hormones, which are much smaller than the instant anelloviridae family vector, one cannot predict variant amino acid sequences for a biologically active virus. As an example related to sequence modifications of a capsid sequence which encodes a proteinaceous exterior from an AAV viral vector, it is known that a single nucleotide change such as the 251/503 sites of AAV capsid can significantly alter the in vivo gene expression of the exogenously delivered gene. (see Mao 2016, BMC Biotechnology, page 1 abstract/conclusion).
To put the situation in perspective, claim 7 recites the genetic element comprises a nucleotide sequence comprising at least 75% sequence identity to nucleotides 1-423 of SEQ ID NO: 54. That 25 percent variance results in a situation in which even if a 423 contiguous nucleotide region is independently varied among the 4 different nucleotides (4234), there would be 32,015,587,041 possible combinations. In fact, since the variation could occur at any position, the actual number of different molecules is orders of magnitude greater than 32,015,587,041. Thus, the Specification fails to overcome the unpredictability of reducing to practice the large numbers of nucleotide deletions/substitutions/insertions/additions in the sequences of SEQ ID NO:1, 5, 54, 58, and 251 and still retain the contemplated function delivering an exogenous effector to the PEC of the RPE.
The Specification fails to provide an adequate written description to support the breadth of the claims as only a RING2, RING19, and CAV vector with corresponding genetic elements and proteinaceous exteriors (see listed examples above). Therefore, the specification does not describe the claimed variation anelloviridae vectors and sequence identity for the genetic elements and proteinaceous exteriors in such full, clear, concise and exact terms so as to indicate that Applicant has possession of these vectors at the time of filing the present application. Thus, it is concluded that the written description requirement is not satisfied for the claimed genera.
Claim Rejections - 35 USC § 102
Claim 12 and 37 are interpreted such that the method of claim 1 has limitations (i)-(iii/iv) are in the alternative based on the recitation “and/or” (i.e. can be “or”).
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 12, 15, 16, 21, 35-41, are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Weinstein et al (WO 2020123773 A2; as cited in IDS) and as evidenced by Reiter (Frontiers in Medicine, 2026, pages 1-21).
The applied Weinstein reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(1). The publication dated for Weinstein is 06/18/2020. The earliest effective filing date of the instant application is 03/16/2022.
Therefore rejection under 35 U.S.C. 103 CANNOT be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(c) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02. Because the reference qualifies as prior art under 102(a)(1), the provisions of MPEP 717.02 do not apply.
Regarding claim 1, 15, 16, 21, 40, and 41, Weinstein teaches a method of delivering an exogenous effector comprising specifically administering an anellosome (e.g., an Anellovirus particle) viral vector comprising a genetic element which encodes an effector and is encapsulated in a proteinaceous exterior (e.g., a proteinaceous exterior comprising an Anellovirus capsid protein) to a cell (e.g., a cell in a subject to be treated therapeutically) (page 1, line 23-25; page 8, line 18-24). Weinstein teaches that the disease treated by the exogenous effector is retinopathy and is age-related macular degeneration (e.g., wet AMD or dry AMD) (page 20, line 1-3), which are diseases related to the retinal pigmented epithelium (RPE) as evidenced by Reiter (“dry and
wet AMD share overlapping pathophysiological features, marked by degeneration
of the RPE”; Abstract), hence the method comprises administrating the viral vector to the posterior eye cup (PEC) or the retinal pigmented epithelium (RPE). Thus, Weinstein anticipates a method of delivering an exogenous effector to the posterior eye cup (PEC) or the retinal pigmented epithelium (RPE) of a subject, the method comprising administering to the PEC or the RPE of the subject an Anelloviridae family vector comprising: (i) a genetic element comprising a nucleic acid sequence encoding an exogenous effector; and (ii) a proteinaceous exterior encapsulating the genetic element (claim 1), wherein the subject has macular degeneration (claim 15), and wherein the subject has a retinal disease (claim 16), and a method of treating a disease or disorder selected from a polygenic disease, a macular degeneration, a retinal disease, the method comprising administering to the subject an Anelloviridae family vector (claim 21), wherein the subject has age-related macular degeneration (AMD) (claim 40), and wherein the subject has wet AMD or dry AMD (claim 41).
Regarding claim 12, the teachings of Weinstein anticipate claim 1. Moreover, Weinstein teaches the method treats a disorder or a disease in a subject and the disease is a cardiovascular or metabolic disease, which are polygenic diseases (page 19, line 25).
Regarding claim 35, the teachings of Weinstein anticipate claim 1. Moreover, Weinstein teaches the anellosome comprises a genetic element encapsulated in a proteinaceous exterior (e.g., an Anellovirus ORF1 protein or a polypeptide encoded by an Anellovirus ORF1 nucleic acid) (page 1, line 23-25), hence Weinstein anticipates wherein the proteinaceous exterior comprises an ORF1 molecule.
Regarding claim 36, the teachings of Weinstein anticipate claim 1 and 35. Moreover, Weinstein teaches the ORF1 molecule (comprised by the anellosome) comprises a jelly-roll domain (page 61, line 1-5), hence Weinstein anticipates the ORF1 molecule comprises a jelly-roll domain.
Regarding claim 37, the teachings of Weinstein anticipate claim 1. Moreover, Weinstein teaches the genetic element of an anellosome of the present disclosure is typically a circular and/or single-stranded DNA molecule (page 1-2, line 33-1) hence Weinstein anticipates wherein the genetic element: (i) is single-stranded; (ii) is circular; and (iv) comprises DNA.
Regarding claim 38 and 39, the teachings of Weinstein anticipate claim 1. Moreover, Weinstein teaches that the genetic element a genetic element encoding the exogenous effector is a therapeutic DNA sequence (page 1, line 23-25), hence Weinstein anticipates wherein the exogenous effector comprises a therapeutic agent (claim 38) and wherein the exogenous effector comprises or a therapeutic nucleic acid (claim 39).
Claim Rejections - 35 USC § 103
Claim 4, 5, 7 and 10 are interpreted such that the method of claim 1 has limitations (i)-(ii/iii) are in the alternative based on the recitation “and/or” (i.e. can be “or”).
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 3-5, 7, and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Weinstein et al (WO 2020123773 A2; as cited in IDS) and further in view of Noteborn et al (WO 9204446 A1; hereinafter termed “Noteborn 1992”), Biagini et al (J. of General Virology, 2007, pages 2696–2701), Galmès et al (Pulmonary Infection, 2013, pages 470-479), Noteborn et al (US 5922600 A; hereinafter termed “Noteborn 1999”), and as evidenced by Reiter (Frontiers in Medicine, 2026, pages 1-21).
Regarding claim 1, Weinstein teaches a method of delivering an exogenous effector comprising specifically administering an anellosome (e.g., an Anellovirus particle) viral vector comprising a genetic element (e.g., a genetic element comprising a therapeutic DNA sequence) encapsulated in a proteinaceous exterior (e.g., a proteinaceous exterior comprising an Anellovirus capsid protein) to a cell (e.g., a cell in a subject to be treated therapeutically) (page 1, Summary; page 8, line 18-24). Weinstein teaches that the disease treated by the exogenous effector is retinopathy and is age-related macular degeneration (page 20, line 1-3), which are diseases related to the retinal pigmented epithelium (RPE) as evidenced by Reiter (“dry and wet AMD share overlapping pathophysiological features, marked by degeneration of the RPE”; Abstract), hence the method comprises administrating the viral vector to the posterior eye cup (PEC) or the retinal pigmented epithelium (RPE). Thus, Weinstein anticipates a method of delivering an exogenous effector to the posterior eye cup (PEC) or the retinal pigmented epithelium (RPE) of a subject, the method comprising administering to the PEC or the RPE of the subject an Anelloviridae family vector comprising: (i) a genetic element comprising a nucleic acid sequence encoding an exogenous effector; and (ii) a proteinaceous exterior encapsulating the genetic element (claim 1).
Regarding claims 3 and 10, the teachings of Weinstein anticipate claim 1.
Weinstein does not teach wherein the genetic element comprises:
the nucleic acid sequence of nucleotides 1-71 of SEQ ID NO: 1 or a complement thereof, or a nucleic acid sequence having at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;
(ii) the nucleic acid sequence of nucleotides 323-393 of SEQ ID NO: 54 or a complement thereof, or a nucleic acid sequence having at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; or
(iii) the nucleic acid sequence of nucleotides 1-374 of SEQ ID NO: 5 or a complement thereof, or a nucleic acid sequence having at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto.
Noteborn 1992 teaches a Chicken Anemia Virus (CAV)-specific nucleotide sequence (as seen in Figure 1) and the use thereof for diagnostics, vaccination or protein production in viral particles which has 100% sequence identity to nucleotides 1-374 of SEQ ID NO: 5. See alignment below:
Qy = instant application nucleotides 1-374 of SEQ ID NO: 5; Db = Noteborn
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Regarding claim 4, the teachings of Weinstein anticipate claim 1.
Weinstein does not teach wherein the genetic element comprises:
the nucleic acid sequence of nucleotides 1-100 of SEQ ID NO: 1 or a complement thereof, or a nucleic acid sequence having at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and/or
(ii) the nucleic acid sequence of nucleotides 2463-2876 of SEQ ID NO: 1 or a complement thereof, or a nucleic acid sequence having at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto.
Biagini teaches a Torque Teno Mini Virus (TTV)-like mini virus isolate comprising nucleic acid sequence with 99% identity to nucleotides 1-100 of SEQ ID NO: 1. See sequence alignment below.
Qy = instant application nucleotides 1-100 of SEQ ID NO: 1; Db = Biagini
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245
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It is noted that the genetic element is interpreted as comprising (i) or, in the alternative, (ii) as recited in claim 4.
Regarding claim 5, the teachings of Weinstein anticipate claim 1.
Weinstein does not teach wherein the proteinaceous exterior comprises:
an ORF1 molecule comprising the amino acid sequence of SEQ ID NO: 2, or an amino acid sequence having at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;
an ORF1 molecule comprising the amino acid sequence of SEQ ID NO: 58, or an amino acid sequence having at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; or
a VP1 molecule comprising the amino acid sequence of SEQ ID NO: 251, or an amino acid sequence having at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto.
Noteborn 1999 teaches the amino acid sequence of the VP1 protein of Chicken Anemia Virus (set forth in SEQ ID NO: 3) in a recombinant vector which has 100% sequence identity to SEQ ID NO: 251 of the instant application. See alignment below.
Qy = instant application SEQ ID NO: 251; Db = Noteborn 1999 SEQ ID NO: 3
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Regarding claim 7, the teachings of Weinstein anticipate claim 1.
Weinstein does not teach wherein the genetic element comprises:
the nucleic acid sequence of nucleotides 1-423 of SEQ ID NO: 54 or a complement thereof, or a nucleic acid sequence having at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and/or
the nucleic acid sequence of nucleotides 2813-2979 of SEQ ID NO: 54 or a complement thereof, or a nucleic acid sequence having at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto.
Galmès teaches a nucleic acid sequence encoding a TTV-like mini virus which has 100% sequence identity to nucleotides 1-423 of SEQ ID NO: 54 of the instant application. See alignment below:
Qy= instant application nucleotides 1-423 of SEQ ID NO: 54; Db = Galmès
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****
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Weinstein et al and further in view of Kiss (Retinal Physician, 2020, pages 1-8).
Regarding claim 17, Weinstein teaches a method of delivering an exogenous effector comprising specifically administering an anellosome (e.g., an Anellovirus particle) viral vector comprising a genetic element (e.g., a genetic element comprising a therapeutic DNA sequence) encapsulated in a proteinaceous exterior (e.g., a proteinaceous exterior comprising an Anellovirus capsid protein) to a cell (e.g., a cell in a subject to be treated therapeutically) (page 1, Summary; page 8, line 18-24). Weinstein teaches that the disease treated by the exogenous effector is retinopathy and is age-related macular degeneration (page 20, line 1-3).
Weinstein does not teach that the method of delivering an effector to a subject, comprises subretinally or intravitreally administering to the subject an Anelloviridae family vector.
Kiss teaches that ocular gene delivery may be accomplished via various route and that intravitreal injection and subretinal surgical delivery are the 2 most common routes of administering a viral-based therapy for retinal disease (Routes of Delivery, page 5-6).
It would have been prima facie obvious to one of ordinary skill, in the art at the time of the effective filing date, to administer the exogenous effector of Weinstein to treat ocular diseases via subretinal or intravitral administration since Kiss teaches that delivery of viral gene therapies for ocular diseases is typically accomplished by intravitreal injection and subretinal surgical delivery. One would be motivated to do so to ensure the effector is efficiently delivered to the subject and have a reasonable expectation of success.
Provisional Statutory Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 1, 3-5, 7,10, 12, 15-17, 21, 35-41 are provisionally rejected under 35 U.S.C. 101 as claiming the same invention as that of claim 23 of copending Application No. 18/700524 (reference application).
Claim 23 of co-pending application 18/700524 recites “A method of delivering an effector (e.g., an exogenous effector or an endogenous effector, e.g., overexpressing an endogenous effector) to an eye of the subject (e.g., to a photoreceptor, retina, posterior eye cup (PEC), optic nerve, optic nerve head, intravitreal space, subretinal space, retinal ganglion, or retinal pigmented epithelium (RPE) of the subject), the method comprising administering to the eye of the subject (e.g., to a photoreceptor, retina, posterior eye cup (PEC), optic nerve, optic nerve head, intravitreal space, subretinal space, retinal ganglion, or retinal pigmented epithelium (RPE) of the subject) an Anelloviridae family vector (e.g., an anellovector)”.
Claim 1 of the instant application recites “A method of delivering an exogenous effector to the posterior eye cup (PEC) or the retinal pigmented epithelium (RPE) of a subject, the method comprising administering to the PEC or the RPE of the subject an Anelloviridae family vector comprising: (i) a genetic element comprising a nucleic acid sequence encoding an exogenous effector; and (ii) a proteinaceous exterior encapsulating the genetic element.” Hence, the active step of “delivering an exogenous effector to the posterior eye cup (PEC) or the retinal pigmented epithelium (RPE) of a subject, the method comprising administering to the PEC or the RPE of the subject an Anelloviridae family vector” is anticipated by Claim 23 of co-pending application 18/700524.
This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented.
Conclusion
No claims are allowed.
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/JULIANA IRENE CANDELARIA/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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