DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Invention I, claims 26, 28-32, 34, 37-39, & 42, and the required species, in the reply filed on 12/26/2025 is acknowledged.
Claims 44, 48-49, 52, 56, 58, and 60-62 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, Claim 37 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/26/2025.
Applicant elected the following species:
Group A) A specific peptide encoded by the isolated nucleic acid molecule: SEQ ID NO: 8.
Group B) A specific nucleic acid molecule sequence that corresponds to the elected peptide sequence: SEQ ID NO: 23.
Amended claims 26, 28-32, 34, 38-39, and 42 are under examination on the merits.
Information Disclosure Statement
The Information Disclosure Statements (IDSs) submitted on 10/19/2022, 10/27/2022, 7/20/2024, and 5/30/2025 are in compliance with 37 CFR 1.97. Accordingly, the IDSs are being considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Interpretation
The specification indicates an "isolated" biological component (such as a nucleic acid molecule, protein, or virus) has been substantially separated or purified away from other biological components (e.g., other chromosomal and extra-chromosomal DNA and RNA, proteins and/or organelles (spec., para [0176]). For purposes of examination, and in the interest of compact prosecution, the examiner is interpreting the term “isolated” to include nucleic acid molecules that are encapsidated in AAV particles, as indicated by claim 39 ([a] recombinant AAV vector, comprising the isolated nucleic acid molecule”).
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on p. 69 (“https:www.pymo.org:2/)”. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http://, www, or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claim 29 is objected to because of the following informalities: line 3 contains a typographical mistake, where “particle” should instead be “particles”. Appropriate correction is required.
Claim 32 is objected to because of the following informalities: on line 3, claim 32 recites “a lipid, or a nucleic acid polymer, or to a combination thereof”, but should instead recite “a lipid, a nucleic acid polymer, or a combination thereof”. Appropriate correction is required.
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 26, 28-31, 34 & 38 are rejected under 35 U.S.C. 101 because:
the claimed invention is directed to a natural phenomenon without significantly more. The claims recite an isolated nucleic acid molecule, comprising: a nucleic acid sequence encoding a polypeptide for modulating the formation of extracellular vesicles and/or AAV particles in cells and/or the secretion of extracellular vesicles and/or AAV particles from cells, wherein the encoded polypeptide comprises a membrane-associated accessory protein (MAAP) or a fragment thereof. This judicial exception is not integrated into a practical application because the claims read on natural AAV genomes, which would possess a nucleic acid molecule comprising a nucleic acid sequence encoding a MAAP polypeptide that would inherently have the functions of modulating the formation and/or secretion of extracellular vesicles and/or AAV particles in cells. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because although the claims indicate that the nucleic acid molecule is “isolated”, the claims still read on an AAV genome, which encodes a MAAP, and an AAV genome is a natural product.
The claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. These claims are analyzed for eligibility in accordance with their broadest reasonable interpretation. In view of the Subject Matter Eligibility Test for Products and Processes and the Steps cited below.
In this case, claims 26, 28-31, 34, & 38 recite or are directed to a composition of matter (Step 1) and are drawn to a product of nature (Step 2A). As disclosed by Ogden (Science. 2019 Nov 29;366(6469):1139-1143), MAAP is an frameshifted gene in the VP1 region that modulates AAV production (Abstract).
Further, in view of Step 2B and the “No” pathway, the claims do not recite additional elements that amount to significantly more than the judicial exception. Thus, the claims as a whole do not amount to significantly more than the exception. It is asserted that the claims are directed to judicial exceptions by reciting a natural product, a nucleic acid sequence encoding an AAV MAAP. The additional claim limitations regarding modulating the formation or secretion of extracellular vesicles and/or AAV particles in cells are inherent properties of the MAAP-encoding nucleic acid sequence, which is a part of the natural product, AAV genome (see Ogden and instant disclosure). Further, the claimed sequence SEQ ID NO: 8 appears to be a natural sequence (spec., Table 1). Therefore, claims 26, 28-31, 34, & 38 do not recite eligible subject matter under 35 U.S.C. 101 in view of the Subject Matter Eligibility Test for Products and Processes.
Applicant is directed towards the USPTO memos, which support this analysis of the claims (https://www.uspto.gov/patent/laws-and-regulations/examination-policy/subject-matter-eligibility); please review the latest materials regarding 35 USC 101 rejections.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 26, 28-32, 39, and 42 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 following quotation from section 2163 of the Manual of Patent Examination Procedure is a brief discussion of what is required in a specification to satisfy the 35 U.S.C. 112 written description requirements for a generic claim covering several distinct inventions:
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice .... reduction to drawings .... or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus... See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
Thus, when a claim covers a genus of inventions, the specification must provide written description support for the entire scope of the genus. Support for a genus is generally found where the applicant has provided a number of examples sufficient so that one in the art would recognize from the specification the scope of what is being claimed.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, or any combination thereof.
Claims 26, 28-32, 39, and 42 are drawn to an isolated nucleic acid molecule, comprising a nucleic acid sequence encoding a polypeptide that comprises a MAAP or a fragment thereof, for modulating the formation and/or secretion of extracellular vesicles and/or AAV particles, a relatively broad limitation, yet limited structure is provided by the disclosure. The specification identifies particular regions of MAAP from AAV8 which are critical for expression and AAV secretion (Example 7 and Fig. 3B-J). Further, the disclosure shows that overexpressed MAAP8 promotes secretion of a specific type of a spherical, extracellular vesicle that is between 20-50 nm in diameter (Example 10, Fig. 5). However, the specification fails to demonstrate the capacities of each MAAP, or specific fragment thereof, for modulating the formation and/or secretion of extracellular vesicles and/or AAV particles.
Regarding the structure function correlation, the structure involves the MAAP or fragment thereof that confers the claimed function of modulating the formation and/or secretion of extracellular vesicles and/or AAV particles. While Applicant has made and tested many MAAP mutants for AAV8 and several other AAV serotypes, the number is not commensurate in scope with the size of the claimed genus, a generic fragment of a generic MAAP. The specification does not provide concrete structure that correlates with the required function.
Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed invention. Applicant is in possession of a number of isolated nucleic acid molecules encoding MAAPs or fragments or mutants thereof, particularly of the MAAP originating from AAV8.
Claims 26, 28-32, 34, 38-39, and 42 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 an isolated nucleic acid molecule, comprising a nucleic acid sequence encoding a full-length AAV MAAP, for modulating the formation of extracellular vesicles and/or AAV particles in cells and/or the secretion of extracellular vesicles and/or AAV particles from cells, does not reasonably provide enablement for an isolated nucleic acid molecule, comprising a nucleic acid sequence encoding a generic fragment of an AAV MAAP for modulating the formation of extracellular vesicles and/or AAV particles in cells and/or the secretion of extracellular vesicles and/or AAV particles from cells. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
Nature of the invention/Breadth of the claims. The claimed invention encompasses an isolated nucleic acid molecule, comprising: a nucleic acid sequence encoding a polypeptide for modulating the formation of extracellular vesicles and/or AAV particles in cells and/or the secretion of extracellular vesicles and/or AAV particles from cells, wherein the encoded polypeptide comprises a membrane-associated accessory protein (MAAP) or a fragment thereof (claim 26). Other embodiments of the claimed invention encompass a recombinant adeno-associated virus (AAV) vector, comprising the isolated nucleic acid molecule (claim 39), or wherein the vector further comprises a promoter operably linked to the isolated nucleic acid molecule, wherein the promoter drives the expression of the encoded polypeptide (claim 42).
In specific embodiments, the encoded polypeptide modulates the formation of extracellular vesicles and/or AAV particles (claim 28), or the rate or efficiency of the secretion of extracellular vesicle and/or AAV particle from the cells (claim 29). In more specific embodiments, modulating comprises increasing (claim 30), or decreasing (claim 31) the rate or efficiency of extracellular vesicle and/or AAV particle secretion from the cells.
In another embodiment, the MAAP or fragment thereof is fused to one or more of a polypeptide, a glycopeptide, a polysaccharide, a glycolipid, a lipid, a nucleic acid polymer, or to a combination thereof (claim 32). In other embodiments, the encoded polypeptide comprises the sequence SEQ ID NO: 8 (claim 34) or SEQ ID NO: 23 (claim 38).
The claims are very broad, since not only do they encompass an isolated nucleic acid molecule encoding a MAAP protein with the claimed functions, but they also encompass a generic fragment of a MAAP protein with the same function.
State of the art/Predictability of the art. The art teaches that protein chemistry is probably one of the most unpredictable areas of biotechnology. For example, replacement of a single “lysine” residue at position 118 of acidic fibroblast growth factor by “glutamic acid” led to the substantial loss of heparin binding, receptor binding and biological activity of the protein (Burgess et al., J of Cell Bio. 111:2129-2138, 1990). In transforming growth factor alpha, replacement of aspartic acid at position 47 with alanine or asparagine did not affect biological activity while replacement with serine or glutamic acid sharply reduced the biological activity of the mitogen (Lazar et al. Molecular and Cellular Biology 8:1247-1252, 1988). As these references illustrate, it is unpredictable that a polypeptide variant of a known target protein binder will also bind said target. It is also unpredictable that they would bind said target in the same way, having the same effect on the target (i.e. inhibit or activate). Ju (Proceedings of the National Academy of Sciences, U.S.A., Vol. 88, Pg. 2658-2662, 1991) teaches that the interleukin 1 receptor (IL-1R) antagonist IL-1ra is a naturally occurring protein with no agonist activity in vitro or in vivo (Abstract). However, substitution of a single amino acid lysine145 to aspartic acid changes the property of this peptide to a partial agonist of IL-1R (Abstract). Thus, even a single substitution can change the biological property of a peptide.
This substitution need not be at a position where said residue would contact the target protein. Baker (Immunity, Vol. 13, Pg. 475-484, 2000) teaches that Tax-peptide is an agonist of the of T cell activity (Abstract). However, mutation of proline at position 6 of this peptide to alanine creates a T cell antagonist (Abstract). Importantly, this residue does not contact the T cell receptor (Abstract).
In another case, Huang (The Journal of Biological Chemistry, Vol. 272, No. 43, Pg. 27155-27159, 1997) teaches that conjugation of peptides to other proteins can change their biological properties. They teach that multiple conjugation of the peptide TGFβ1 (residues 41-65) to carrier proteins enhances its antagonist activity but also confers partial agonist activity as well (Abstract). Thus, the chemical context of a biologically active peptide is also important.
Truncation of proteins can also lead to adverse effects on protein structure and thus protein function. Martindale (Nature Genetics, Vol. 18, Pg. 150-154, 1998) teaches that truncation of huntingtin leads to aggregate development which compromises cell viability (Abstract). Nonaka (Human Molecular Genetics, Vol. 18, No. 18, Pg. 3353-3364, 2009) teaches that truncation of TDP-43 to its C-terminal fragments causes abnormally phosphorylated and ubiquitinated inclusions of the protein (Abstract). Taken together, not just any truncation of a protein will yield a soluble, functional, protein fragment.
In summary, these examples teach that the biological function of peptide variants is unpredictable because even a single mutation can abolish activity or give a different function. For example, agonist and antagonist peptides can be interconverted through conjugation or mutagenesis. Importantly, binding can still occur after mutation or conjugation in the literature examples provided above, illustrating that a simple show of binding is not predictive of the nature of a peptide’s biological activity. This point is underlined by Montrose-Rafizadeh (The Journal of Biological Chemistry, Vol. 272, Pg. 21201-21206, 1997) who teaches that receptor binding does not predict agonist or antagonist activity (Pg. 21205, Column 2, Paragraph, first full, Sentence, first).
With respect to the use of peptides in the modulation of particular processes, the state of the art at the time of filing was such that it was unpredictable whether or not a peptide would function therapeutically. Their functionality depends, in part, on whether or not they reach their intended target in a sufficient quantity as to cause a therapeutic effect. Mendoza (Arch. Immunol. Ther. Exp., Vol. 53, Pg. 47-60, 2005) teaches that peptides derived from larger molecules that are important modulators of apoptosis are frequently becoming leads for the development of anticancer therapeutics (Pg. 48, Column 2, Paragraph, first partial). However, they also state that natural peptides have low bioavailability and short half-life in the mammalian circulation system, while synthetic peptides have potential cytotoxicities (Pg. 57, Column 1, Paragraph, last full). Due to these characteristics, systematic testing in in vivo as well as in vitro settings must be done rigorously to verify peptide applications in the clinic (Pg. 57, Column 1, Paragraph, last full). Taken together, barring experimental evidence, no peptide can merely be assumed to function in the modulation of a process, for example cancer, in vivo just because it functions as an inhibitor in vitro.
Working examples/Guidance in the specification. The disclosure states that MAAPs share conserved N-and C- terminal regions (Example 1), MAAP’s cationic, amphipathic C-terminal domain associates with cell surface and subcellular membrane (Example 2), not all MAAPs are tightly clustered (Example 3), AAV1, AAV2, AAV5, AAV8, and AAV9 MAAPs fused to C-terminal GFP associate with cell surface and subcellular organelle membranes (Example 4).
The disclosure also identifies particular regions of MAAP from AAV8 which are critical for expression and AAV secretion (Example 7 and Fig. 3B-J). Further, the disclosure shows that overexpressed MAAP8 promotes secretion of a specific type of a spherical, extracellular vesicle that is between 20-50 nm in diameter (Example 10, Fig. 5).
Amount of experimentation necessary. There would be undue experimentation for one of ordinary skill in the art to make or use the claimed invention when considering the breadth of the claims, nature of the invention, and prior art. Notably, the claims are relatively broad, claiming a generic fragment of a MAAP. As discussed above, a single mutation, even when not in an interaction domain, or truncation can result in the loss of a peptide’s function. The disclosure’s working examples do not support the very broad claimed group of MAAP peptides that maintain modulatory functions of formation of extracellular vesicles and/or AAV particles in cells and/or the secretion of extracellular vesicles and/or AAV particles from cells.
Since the art teaches that it is unpredictable whether or not peptide variants of known modulators will function as such and it is also unpredictable that even a known modulatory peptide that functions in vitro will function in vivo, and the specification does nothing to ameliorate these concerns, one would be burdened with undue experimentation to use the products of instant claims as broadly as they are currently claimed.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 26, 28-32, 34, 38-39, and 42 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.
The term “isolated” in claims 26, 28-32, 34, & 38 renders the claims indefinite. The term “isolated” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Rather, the specification indicates that “isolated” means to be substantially separated or purified away (spec., para. [0176]), which is indefinite because “substantially” is a relative term. Further, the specification indicates that “[t]he term ‘isolated’ (or purified) does not require absolute purity: rather, it is intended as a relative term” (Id.; emphasis added). Since two practitioners could have different definitions of substantially and relatively isolated, the claims have multiple interpretations. It is suggested that Applicant consider use of purified instead if support can be found for it. “A claim may be rendered indefinite when a limitation of the claim is defined by reference to an object and the relationship between the limitation and the object is not sufficiently defined. That is, where the elements of a claim have two or more plausible constructions such that the examiner cannot readily ascertain positional relationship of the elements, the claim may be rendered indefinite.” See, e.g., Ex parte Miyazaki, 89 USPQ2d 1207 (Bd. Pat. App. & Inter. 2008). MPEP §2173.05(b).
Claim Rejections – Improper Markush Grouping
Claims 34 and 38 are rejected on the judicially-created basis that they contain an improper Markush grouping of alternatives.
See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984).
The improper Markush grouping includes species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature. The members of the improper Markush grouping do not share a substantial structural feature and a common use that flows from the substantial structural feature for the following reasons:
MPEP 803.02 provides guidance on the analysis of a proper Markush group. Members of a proper Markush group are disclosed in the specification to possess at least one property in common which is mainly responsible for their function in the claimed relationship, and it is clear from their very nature or from the prior art that all of them possess this property. The MPEP further provides that in the members of a proper Markush group there should be (1) a common utility, and (2) a substantial structural feature essential to that utility.
In the instant case, the group of membrane-associated accessory proteins (MAAPs) SEQ ID NOs: 01-15 (claim 34), or the nucleic acid sequences that encode the MAAPs contain species with different sequences. The MAAPs appear to modulate the formation of extracellular vesicles and/or AAV particles in cells and/or the secretion of extracellular vesicles and/or AAV particles from cells (claim 26; specification in general). However, the amino acid sequences of the MAAPs are varied, and do not appear to have conserved domains. Thus, it is not apparent which domains or residues are associated with the claimed functions Since the instant claims contain Markush groups with members of MAAPs with differing sequences lacking shared, discernable, discrete domains associated with the claimed functions of modulating the formation of extracellular vesicles and/or AAV particles in the cells, or the secretion of extracellular vesicles and/or AAV particles from the cells, the claims contain an improper Markush group and are rejected here.
In response to this rejection, Applicant should either amend the claim(s) to recite only individual species or grouping of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claims(s) in fact share a substantial structural feature as well as a common use that flows from the substantial structural feature. This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 U.S.C. §134 and 37 CFR 41.31(a)(1).
Claim Rejections - 35 USC § 102
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 (i.e., changing from AIA to pre-AIA ) 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.
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 26, 28-32, 34, 38, 39, and 42 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ogden, et al. (Science. 2019 Nov 29;366(6469):1139-1143; hereinafter referred to as “Ogden”) as evidenced by Elmore, et al. (Nat Commun. 2021 Oct 29;12(1):6239; hereinafter referred to as “Elmore”).
Ogden teaches that AAV encodes a +1 frameshifted ORF in the VP1 region, which is 119 amino acids in length (Fig. 2A; p. 1139, col. 3, para. 3), which they named membrane-associated accessory protein (MAAP; p. 1140, cols 2-3). Ogden further discloses that to validate the ORF’s translation, they added a FLAG tag at the C-terminus and transfected the plasmid into HEK293T cells (p. 1139, col. 3, para. 4). Ogden also created a C-terminal GFP fusion of the ORF, from sequences derived from AAV5, AAV8, and AAV9, in addition to the AAV2 ORF (p. 1140, col. 2, para. 1). Notably, MAAP localized to the cell membrane (Figs. 2C, S6, and S8). Ogden also generated recombinant MAAP-null viruses, including 27ΔStart, where the VP-P27-CCT codon was mutated to CCC, and 32ΔStop, in which the VP-P32-CCT codon was mutated to ATA (V), making an early stop codon in MAAP (Fig. 2D-2E; p. 1140, col. 3; Supplemental materials, pp. 4-5). Ogden also discloses that the MAAP ORF starts with CTG, which is a noncanonical start codon which encodes leucine (p. 1139, col. 3, para. 3). Notably, claims 34 and 38 require the isolated nucleic acid to comprise SEQ ID NO: 23 or encode SEQ ID NO: 8, or fragments thereof. The MAAP encoded by SEQ ID NO: 23 starts with a CTG (leucine), and SEQ ID NO: 8 starts with a leucine—accordingly, Ogden anticipates claims 34 and 38 because it encodes a MAAP that, at the very least, has those bases or amino acid in common with SEQ ID NO: 23 or SEQ ID NO: 8, respectively.
Elmore provides evidence that MAAP is a viral egress factor, with a highly conserved cationic amphipathic domain critical for AAV secretion (Abstract). Elmore further discloses that while AAV with a mutated MAAP (MAAPΔ) start site showed markedly attenuated secretion (including AAV2 and AAV8), and correspondingly increased intracellular retention, trans-complementation with MAAP restored secretion of multiple AAV/MAAPΔ serotypes (Abstract; Fig. 4).
The express, implicit, and inherent disclosures of a prior art reference may be relied upon in the rejection of claims under 35 U.S.C. 102 or 103. MPEP §2112. "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). MPEP §2112(I). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003). MPEP §2112((II). The MAAP and recombinant AAV mutants disclosed by Ogden inherently have the claimed characteristics of modulating the formation of extracellular vesicles and/or AAV particles, modulating (i.e., increasing) the rate or efficiency of the secretion of extracellular vesicle and/or AAV particles from cells, as demonstrated by Elmore. Similarly, the recombinant AAV viruses disclosed by Ogden would inherently comprise a promoter operably linked to the isolated nucleic acid molecule, wherein the promoter drives the expression of the encoded polypeptide, because of the native AAV promoter.
Therefore, claims 26, 28-32, 34, 38, 39, and 42 are anticipated by Ogden as evidenced by Elmore.
Claims 26, 28-30, 34, 38, 39, and 42 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Samulski, et al. (PGPub US 20090191597 A1, published 7/30/2009, filed 12/9/2008; hereinafter referred to as “Samulski”) as evidenced by Elmore, et al. (supra).
Samulski discloses methods of producing recombinant adeno-associated viruses (rAAV) in insect cells and uses thereof (para. [0003]). Samulski discloses an AAV8 VP1 encoding sequence, SEQ ID NO: 7, which is 100% identical to the instant SEQ ID NO: 23 (Samulski, SEQ ID NO: 7; para. [0013]). See sequence alignment in ABSS below:
PNG
media_image1.png
116
266
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Greyscale
Further, the +1 frameshift of Samulski’s SEQ ID NO: 7 translated contains a polypeptide that is 100% identical to SEQ ID NO: 8. See sequence alignment from ABSS below:
PNG
media_image2.png
256
802
media_image2.png
Greyscale
Elmore provides evidence that MAAP is a viral egress factor, with a highly conserved cationic amphipathic domain critical for AAV secretion (Abstract). Elmore further discloses that while AAV with a mutated MAAP (MAAPΔ) start site showed markedly attenuated secretion (including AAV2 and AAV8), and correspondingly increased intracellular retention, trans-complementation with MAAP restored secretion of multiple AAV/MAAPΔ serotypes (Abstract; Fig. 4).
The express, implicit, and inherent disclosures of a prior art reference may be relied upon in the rejection of claims under 35 U.S.C. 102 or 103. MPEP §2112. "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). MPEP §2112(I). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003). MPEP §2112((II). The MAAP and recombinant AAV mutants disclosed by Samulski inherently have the claimed characteristics of modulating the formation of extracellular vesicles and/or AAV particles, modulating (i.e., increasing) the rate or efficiency of the secretion of extracellular vesicle and/or AAV particles from cells, as demonstrated by Elmore. Similarly, the recombinant AAV viruses disclosed by Samulski would inherently comprise a promoter operably linked to the isolated nucleic acid molecule, wherein the promoter drives the expression of the encoded polypeptide, because of the native AAV promoter.
Therefore, claims 26, 28-30, 34, 38, 39, and 42 are anticipated by Samulski as evidenced by Elmore.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEFFREY MARK SIFFORD whose telephone number is (571)272-7289. The examiner can normally be reached 8:30 a.m. - 5:30 p.m. ET with alternating Fridays off.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Allen can be reached at 571-270-3497. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JEFFREY MARK SIFFORD/Examiner, Art Unit 1671 /Michael Allen/Supervisory Patent Examiner, Art Unit 1671