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 .
Information Disclosure Statement
The information disclosure statement(s) (IDS) was/were submitted on 4/7/2025, before the mailing of a first office action. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Priority
Priority to US 63/183,702, filed 5/4/2021, is acknowledged.
Claim Status
Claims 1-13, 15, 17-21 are pending. Claims 1-13, 15, and 17-21 are under examination. Claim 16 is missing.
Specification
The use of the term “Scan Image Basic” in para. [0261], which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
The use of the term “Leica CM3050S” in para. [0262] of the specification, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
The use of the term “Alexa Fluor” in para. [0262] and para. [0265], which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
The use of the term “Vectashield” in para. [0262], which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
The use of the term “Leica VT1000S” in para. [0263] of the specification, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
The use of the term “Leica SP8” in para. [0263] of the specification, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
The use of the term “Slidescanner Zeiss Axio” in para. [0263] of the specification, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
The use of the term “Leica VT1000S” in para. [0264] of the specification, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 17-21 are objected to because of the following informalities. The claim set does not contain a claim labeled as 16. The claim set skips from claim 15 to claim 17. Appropriate correction is required.
Claim Rejections - 35 USC § 112
Claims 1-13, 15, and 17-21 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites: “An adeno-associated virus (AAV) targeting peptide comprising an amino acid sequence that comprises at least 4 contiguous amino acids from a sequence selected from the group consisting of GNNTRSV (SEQ ID NO: 13), GNNTRDT (SEQ ID NO: 14) and TNSTRPV (SEQ ID NO: 15).”
MPEP 2173.05(a)(III) states: “Consistent with the well-established axiom in patent law that a patentee or applicant is free to be his or her own lexicographer, a patentee or applicant may use terms in a manner contrary to or inconsistent with one or more of their ordinary meanings if the written description clearly redefines the terms. See, e.g., Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999) ("While we have held many times that a patentee can act as his own lexicographer to specifically define terms of a claim contrary to their ordinary meaning," in such a situation the written description must clearly redefine a claim term "so as to put a reasonable competitor or one reasonably skilled in the art on notice that the patentee intended to so redefine that claim term."); Hormone Research Foundation Inc. v. Genentech Inc., 904 F.2d 1558, 15 USPQ2d 1039 (Fed. Cir. 1990)”.
Furthermore, MPEP 2173.02(II) states: “The essential inquiry pertaining to this requirement is whether the claims set out and circumscribe a particular subject matter with a reasonable degree of clarity and particularity. "As the statutory language of ‘particular[ity]' and 'distinct[ness]' indicates, claims are required to be cast in clear—as opposed to ambiguous, vague, indefinite—terms. It is the claims that notify the public of what is within the protections of the patent, and what is not." Packard, 751 F.3d at 1313, 110 USPQ2d at 1788. Definiteness of claim language must be analyzed, not in a vacuum, but in light of:[AltContent: rect]
(A) The content of the particular application disclosure;
(B) The teachings of the prior art; and
(C) The claim interpretation that would be given by one possessing the ordinary level of skill in the pertinent art at the time the invention was made.”
Applicant refers to both AAV targeting peptides and targeting throughout the specification, such as in para. [0085].
A person of ordinary skill in the art can reasonably interpret the language of claim 1 to mean a peptide that targets AAV, not one that targets AAV to some other target. Furthermore, para. [0088] of the specification attaches said targeting peptide to compositions other than AAV molecules: “The targeting peptide can be conjugated to a nanoparticle, a second molecule, a viral capsid protein, or a combination thereof. The targeting peptide can be a central nervous system (CNS) targeting peptide.”
Of particular note is the sentence “The targeting peptide can be a central nervous system (CNS) targeting peptide.”. In this context, the targeting peptide is clearly meant to actually target the CNS, not assist the CNS targeting some other target.
Removal of the term “adeno-associated virus (AAV)” would alleviate this issue because these peptides would then be referred to as “targeting peptides” which is fully supported by the specification and clearly conveys the invention because these peptides can function as targeting peptides outside the context of AAV.
Consequently, claim 1 is rejected.
Claims 2-13, 15, and 17-21 ultimately refer back to claim 1 and do not resolve this source of indefiniteness.
Consequently, claims 2-13, 15, and 17-21 are rejected.
Regarding claim 13, claim 13 recites the limitation "the targeting AAV peptide" in line 2. There is insufficient antecedent basis for this limitation in the claim. This term has not been used in the claim set.
Furthermore, claim 13 is indefinite because the altered word order of this phrase can be interpreted to claim alanine-alanine-valine.
Consequently, claim 13 is rejected.
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 1-13, 15, and 17-21 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.
Claim 1 is 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.
Claim 1 recites an open-ended number of peptide sequences with a number of possible sub-combinations of the recited contiguous amino acids. This results in a very broad claimed sequence space.
In this case, 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 inventor was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. (MPEP § 2163 (II.A.3.a.ii.))
According to MPEP § 2163 (II.A.3.a.ii.), 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. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014).
As described above, claim 1 recites a huge sequence space of polypeptides.
MPEP § 2163 (II.A.3.a.ii.) states that “for inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’”
Even when several species are disclosed, these are not necessarily representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). Thus, when there is substantial variation within the genus, as here, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. Since each genus recited in the instant claims is large, it would be very challenging to describe sufficient species to cover the structures of the entire genus.
Applicant discloses three examples .
At the time the invention was made, the level of skill for preparing peptides with desired functional properties was high. However, even if a synthesis and selection procedure was, at the time of the invention, sufficient to enable the skilled artisan to identify peptides that yield polypeptides with the recited properties, the written description provision of 35 U.S.C § 112 is severable from its enablement provision. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336 (Fed. Cir. 2010); see also Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1876 (Fed. Cir. 2011) (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”) Absent the conserved structure (length) provided by the provided species, the skilled artisan generally would not be able to visualize or otherwise predict, a priori, what peptide with a particular set of properties would look like structurally.
Applicant discloses 66 examples and reduces those examples to practice. This is a tiny fraction of the claimed sequences, however. Therefore, the provided examples only represent a limited structural diversity.
Since only a limited number of species of peptides are taught within the claimed genus above, the instant claim above fails the written description requirement. A representative number of species has not been taught to describe this genus. Regarding the peptides, a single point mutation can change the biophysical properties of a peptide: “In summary, we have shown that the structural changes in the fibrillar state of the Aβ42 peptide that are observed to occur upon introduction of single point mutations can be accompanied by changes in the dominance of the microscopic processes by which these aggregates are themselves formed.” (Bolognesi et al. ACS Chem Bio 9:2 (2013) page 381 col. 2 para. 3) and “In summary, while ovispirin-1 and novispirin G-10 both had solution structures that were helical and amphipathic in the presence of TFE, a relatively simple change in their primary structure (a single glycine–isoleucine exchange) had profound effects on their respective toxicities for human erythrocytes and epithelial cells.” (Sawai et al. Protein Eng. 15:3 (2002) page 232 col. 1 para. 3).
Furthermore, many sequences allowed by the current scope of the claims, result in non-functional aggregates. Wang (Wang, et al. MAbs. Vol. 1. No. 3. Taylor & Francis, (2009)) discloses a variety of aggregation prone motifs that occur in commercial antibodies (Wang, page 262, Table 2). The scope of the claims currently may incorporate such motifs and result in non-functional aggregates.
Given this unpredictability of protein design, the skilled artisan would not have been in possession of the substantial repertoire of peptide species encompassed by the claimed invention; one of skill in the art would conclude that applicant was not in possession of the structural attributes of a representative number of species possessed by the members of the genus of every polynucleotide molecule recited by claim 1.
Claim 1 is rejected.
Regarding claims 2-13, 15, and 17, these claims all ultimately depend from claim 1. None of the claims sufficiently reduce the sequence space covered to the point where the specification discloses a representative number of species.
Consequently, claims 2-13, 15, and 17 are rejected.
Claim 18 recites: “the AAV capsid protein of claim 17, further comprising at least 4 contiguous amino acids from a second amino acid sequence selected from the group consisting of DGQSSKS (SEQ ID NO: 17), DGAATKN (SEQ ID NO: 16), and LQTSSPG (SEQ ID NO: 18).”
There is no guidance in claim 18 with respect to the relationship between the required amino acids from claim 17 (which is dependent upon claim 1) and the new required amino acids. Because of the comprising transitional phrase, any number of other residues many exist between the sets of required residues. This means this genus encompasses a huge sequence space.
Claim 18 is rejected.
Regarding claims 19-21, the specification also does not disclose a representative number of species for the same reasons as listed for claim 18.
Consequently, claims 19-21 are rejected.
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.
Claim 1 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more. The claims recite peptide sequences found in nature.
Regarding claim 1, claim 1 recites: “An adeno-associated virus (AAV) targeting peptide comprising an amino acid sequence that comprises at least 4 contiguous amino acids from a sequence selected from the group consisting of GNNTRSV (SEQ ID NO: 13), GNNTRDT (SEQ ID NO: 14) and TNSTRPV (SEQ ID NO: 15).”
Step 2A:
Xu et al. (Xu, Zhichao, et al. Gene 574.2: 352-358 (2015)) discloses Cyp3 whose sequence is entered under UnitProt Assession Number V5W4C7 (deposited 2/19/2014):
MSSSSTNSTRPVVFMDVNIGETPAGRLKMELFSDIVPKTAENFRQLCTGEPQGYKGATFHRREAQTVTVGGDFLKGDGTGSFSIYGDKFPDENFKEKHTEPGLLSMANSGPNTNGCQFFVTTAKCDFLDGKHVVFGRVIDGMLTLRKIENVATGANNRPKLVVKIVGTCARRLPNVCAGPHRLIRSPRVW (emphasis added; Xu et al., page 354, Table 1).
This sequence is not markedly different than the claimed sequence because this sequence meets the claim limitations of claim 1. Any required activity is necessarily present because MPEP 2112.01(II) states: “"Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.”
This judicial exception is not integrated into a practical application because the claim is a composition claim that recites a peptide sequence. There is no integration present in the claim.
Step 2B:
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim is a composition claim that recites a peptide sequence. Similar to the integration analysis above, nothing is present in the claim that would amount to “significantly more”.
Consequently, clam 1 is rejected.
Claims 2 and 3 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more. The claims recite peptide sequences found in nature.
Regarding claim 2, claim 2 recites: “The AAV targeting peptide of claim 1, wherein the targeting peptide comprises at least 5 contiguous amino acids from the sequence of GNNTRSV (SEQ ID NO: 13).”
Step 2A:
Paulsen et al. (Paulsen, et al. Nature biotechnology 23.7: 873-878. (2005)) discloses RNA methyltransferase (Pseudomonas fluorescens strain Pf-5) whose sequence is entered in UniProt Assession No. Q4KGK4 (Deposited 8/2/2005):
MANKRYSCIGLYNPKSPENVGSVMRAAGCYGVASVFYTGKRYERARDFVTDTKKVHQDIPLIGIDDLKKILPLGCIPVAVELVEGARPLPEYTHPDRALYIFGPEDGSLDKEIRDWCEDVVYIPTTGCMNLAATVNVVLYDRLAKGNNTRSGPKF (emphasis added, results of Paulsen were catalogued in UniProt and GenBank).
This sequence is not markedly different than the claimed sequence because this sequence meets the claim limitations of claim 2. Any required activity is necessarily present because MPEP 2112.01(II) states: “"Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.”
This judicial exception is not integrated into a practical application because the claim is a composition claim that recites a peptide sequence. There is no integration present in the claim.
Step 2B:
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim is a composition claim that recites a peptide sequence. Similar to the integration analysis above, nothing is present in the claim that would amount to “significantly more”.
Consequently, clam 2 is rejected.
Regarding claim 3, claim 3 recites: “The AAV targeting peptide of claim 1, wherein the targeting peptide comprises at least 6 contiguous amino acids from the sequence of GNNTRSV (SEQ ID NO: 13).”
Step 2A:
Paulsen et al. (Paulsen, et al. Nature biotechnology 23.7: 873-878. (2005)) discloses RNA methyltransferase (Pseudomonas fluorescens strain Pf-5) whose sequence is entered in UniProt Assession No. Q4KGK4 (Deposited 8/2/2005):
MANKRYSCIGLYNPKSPENVGSVMRAAGCYGVASVFYTGKRYERARDFVTDTKKVHQDIPLIGIDDLKKILPLGCIPVAVELVEGARPLPEYTHPDRALYIFGPEDGSLDKEIRDWCEDVVYIPTTGCMNLAATVNVVLYDRLAKGNNTRSGPKF (emphasis added, results of Paulsen were catalogued in UniProt and GenBank).
This sequence is not markedly different than the claimed sequence because this sequence meets the claim limitations of claim 3. Any required activity is necessarily present because MPEP 2112.01(II) states: “"Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.”
This judicial exception is not integrated into a practical application because the claim is a composition claim that recites a peptide sequence. There is no integration present in the claim.
Step 2B:
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim is a composition claim that recites a peptide sequence. Similar to the integration analysis above, nothing is present in the claim that would amount to “significantly more”.
Consequently, clam 3 is rejected.
Claim 4 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more. The claims recite peptide sequences found in nature.
Regarding claim 4, claim 4 recites: “The AAV targeting peptide of claim 1, wherein the targeting peptide comprises GNNTRSV (SEQ ID NO: 13).”
Step 2A:
UniProt Accession No. V8NWD4_OPHHA discloses the following sequence (Deposited 2/19/2014):
MQNQPVGTPSSGREGQPSEMLKDLILRWFLETQIVLLLQDGRLPDWFHGFLSRQEAEMLLENKEFGCFLIRLNEKAFGYILSYRGKDRCRHFVISCHRSGRYLVSGDSQTHAQLAELISYYQRSPSADAPTLSRNPSADLLVTRSHFTNQPGHPRIPLQKEQKSLFKEPQNAKEDPDEAPPIPDRSRLLESLSLEEEVGDEGTIYSAVKKPPLDKKSLGKSKEGGRNFGDTKAKEPVGPGQGLSSPCQRKTGTMFGLAKRSDTPFTIKVNPAERAQTGTIYSRIAFDQPKTFWIPAEPPSYQSTCPSSKKSAVPNYPPLKLSPTLPNKSKYSVAFHGSPLGNNTRSVGNKEHGQLNQPKSLFELPKDHTGEKIFQLKNQPSALWADNTTNTQESFRWAKSIFLGSEKPPKASLTRSKGSYDQISAKFGHVSKIQINPESPYEKITDPYSHCSSATSQAASLEDPYEQIPYLPGKRIEGKVTPKSEKPRKFLFTDKKAKS
This sequence is not markedly different than the claimed sequence because this sequence meets the claim limitations of claim 4. Any required activity is necessarily present because MPEP 2112.01(II) states: “"Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.”
This judicial exception is not integrated into a practical application because the claim is a composition claim that recites a peptide sequence. There is no integration present in the claim.
Step 2B:
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim is a composition claim that recites a peptide sequence. Similar to the integration analysis above, nothing is present in the claim that would amount to “significantly more”.
Consequently, clam 4 is rejected.
Regarding claim 4, claim 4 recites: “The AAV targeting peptide of claim 1, wherein the targeting peptide comprises GNNTRSV (SEQ ID NO: 13).”
Step 2A:
UniProt Accession No. V8NWD4_OPHHA discloses the following sequence (Deposited 2/19/2014):
MQNQPVGTPSSGREGQPSEMLKDLILRWFLETQIVLLLQDGRLPDWFHGFLSRQEAEMLLENKEFGCFLIRLNEKAFGYILSYRGKDRCRHFVISCHRSGRYLVSGDSQTHAQLAELISYYQRSPSADAPTLSRNPSADLLVTRSHFTNQPGHPRIPLQKEQKSLFKEPQNAKEDPDEAPPIPDRSRLLESLSLEEEVGDEGTIYSAVKKPPLDKKSLGKSKEGGRNFGDTKAKEPVGPGQGLSSPCQRKTGTMFGLAKRSDTPFTIKVNPAERAQTGTIYSRIAFDQPKTFWIPAEPPSYQSTCPSSKKSAVPNYPPLKLSPTLPNKSKYSVAFHGSPLGNNTRSVGNKEHGQLNQPKSLFELPKDHTGEKIFQLKNQPSALWADNTTNTQESFRWAKSIFLGSEKPPKASLTRSKGSYDQISAKFGHVSKIQINPESPYEKITDPYSHCSSATSQAASLEDPYEQIPYLPGKRIEGKVTPKSEKPRKFLFTDKKAKS
This sequence is not markedly different than the claimed sequence because this sequence meets the claim limitations of claim 4. Any required activity is necessarily present because MPEP 2112.01(II) states: “"Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.”
This judicial exception is not integrated into a practical application because the claim is a composition claim that recites a peptide sequence. There is no integration present in the claim.
Step 2B:
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim is a composition claim that recites a peptide sequence. Similar to the integration analysis above, nothing is present in the claim that would amount to “significantly more”.
Consequently, clam 4 is rejected.
Claims 5-8 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more. The claims recite peptide sequences found in nature.
Regarding claim 5, claim 5 recites: “The AAV targeting peptide of claim 1, wherein the targeting peptide comprises at least 4 contiguous amino acids from the sequence GNNTRDT (SEQ ID NO: 14).”
UniProt Accession No. R0KK08_EXST2 (deposited 6/23/2013) discloses:
MKTLLITLSALTAAVTAASSSGCGKSLPDNVHLGESVNLTIKSESGATPRGYRLHIPPSYEQNTELPLILSFHGRGKDAKFQEALSQFSNASYGFEGIAVYPEGVPNKKGTQQFEGDPDSPKSISDVTFTLELLDHLESTYCIDTSRIYANGKSNGGGFTGILACDAKATKRIAAFAPVSGAFYLDADQQPPPCNPSRKPIPFMEFHGYPDSTIRYQGGNNTRDTASTSDIVTYVNDWARRDGFEPAANKTTHLCSGKKAVTRHSWDDVVVDYNYTNIKHDWPSSFPNGDTDTLLTCEDAEATPIILEWFKKWTI
This sequence is not markedly different than the claimed sequence because this sequence meets the claim limitations of claim 5. Any required activity is necessarily present because MPEP 2112.01(II) states: “"Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.”
This judicial exception is not integrated into a practical application because the claim is a composition claim that recites a peptide sequence. There is no integration present in the claim.
Step 2B:
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim is a composition claim that recites a peptide sequence. Similar to the integration analysis above, nothing is present in the claim that would amount to “significantly more”.
Consequently, clam 5 is rejected.
Regarding claim 6, claim 6 recites: “The AAV targeting peptide of claim 5, wherein the targeting peptide comprises at least 5 contiguous amino acids from the sequence GNNTRDT (SEQ ID NO: 14).”
UniProt Accession No. R0KK08_EXST2 (deposited 6/23/2013) discloses:
MKTLLITLSALTAAVTAASSSGCGKSLPDNVHLGESVNLTIKSESGATPRGYRLHIPPSYEQNTELPLILSFHGRGKDAKFQEALSQFSNASYGFEGIAVYPEGVPNKKGTQQFEGDPDSPKSISDVTFTLELLDHLESTYCIDTSRIYANGKSNGGGFTGILACDAKATKRIAAFAPVSGAFYLDADQQPPPCNPSRKPIPFMEFHGYPDSTIRYQGGNNTRDTASTSDIVTYVNDWARRDGFEPAANKTTHLCSGKKAVTRHSWDDVVVDYNYTNIKHDWPSSFPNGDTDTLLTCEDAEATPIILEWFKKWTI
This sequence is not markedly different than the claimed sequence because this sequence meets the claim limitations of claim 6. Any required activity is necessarily present because MPEP 2112.01(II) states: “"Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.”
This judicial exception is not integrated into a practical application because the claim is a composition claim that recites a peptide sequence. There is no integration present in the claim.
Step 2B:
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim is a composition claim that recites a peptide sequence. Similar to the integration analysis above, nothing is present in the claim that would amount to “significantly more”.
Consequently, clam 6 is rejected.
Regarding claim 7, claim 7 recites: “The AAV targeting peptide of claim 5, wherein the targeting peptide comprises at least 6 contiguous amino acids from the sequence GNNTRDT (SEQ ID NO: 14).”
UniProt Accession No. R0KK08_EXST2 (deposited 6/23/2013) discloses:
MKTLLITLSALTAAVTAASSSGCGKSLPDNVHLGESVNLTIKSESGATPRGYRLHIPPSYEQNTELPLILSFHGRGKDAKFQEALSQFSNASYGFEGIAVYPEGVPNKKGTQQFEGDPDSPKSISDVTFTLELLDHLESTYCIDTSRIYANGKSNGGGFTGILACDAKATKRIAAFAPVSGAFYLDADQQPPPCNPSRKPIPFMEFHGYPDSTIRYQGGNNTRDTASTSDIVTYVNDWARRDGFEPAANKTTHLCSGKKAVTRHSWDDVVVDYNYTNIKHDWPSSFPNGDTDTLLTCEDAEATPIILEWFKKWTI
This sequence is not markedly different than the claimed sequence because this sequence meets the claim limitations of claim 7. Any required activity is necessarily present because MPEP 2112.01(II) states: “"Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.”
This judicial exception is not integrated into a practical application because the claim is a composition claim that recites a peptide sequence. There is no integration present in the claim.
Step 2B:
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim is a composition claim that recites a peptide sequence. Similar to the integration analysis above, nothing is present in the claim that would amount to “significantly more”.
Consequently, clam 7 is rejected.
Regarding claim 8, claim 8 recites: “The AAV targeting peptide of claim 5, wherein the targeting peptide comprises GNNTRDT (SEQ ID NO: 14).”
UniProt Accession No. R0KK08_EXST2 (deposited 6/23/2013) discloses:
MKTLLITLSALTAAVTAASSSGCGKSLPDNVHLGESVNLTIKSESGATPRGYRLHIPPSYEQNTELPLILSFHGRGKDAKFQEALSQFSNASYGFEGIAVYPEGVPNKKGTQQFEGDPDSPKSISDVTFTLELLDHLESTYCIDTSRIYANGKSNGGGFTGILACDAKATKRIAAFAPVSGAFYLDADQQPPPCNPSRKPIPFMEFHGYPDSTIRYQGGNNTRDTASTSDIVTYVNDWARRDGFEPAANKTTHLCSGKKAVTRHSWDDVVVDYNYTNIKHDWPSSFPNGDTDTLLTCEDAEATPIILEWFKKWTI
This sequence is not markedly different than the claimed sequence because this sequence meets the claim limitations of claim 8. Any required activity is necessarily present because MPEP 2112.01(II) states: “"Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.”
This judicial exception is not integrated into a practical application because the claim is a composition claim that recites a peptide sequence. There is no integration present in the claim.
Step 2B:
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim is a composition claim that recites a peptide sequence. Similar to the integration analysis above, nothing is present in the claim that would amount to “significantly more”.
Consequently, clam 8 is rejected.
Claims 9-12 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more. The claims recite peptide sequences found in nature.
Regarding claim 9, claim 9 recites: “The AAV targeting peptide of claim 1, wherein the targeting peptide comprises at least 4 contiguous amino acids from the sequence TNSTRPV (SEQ ID NO: 15).”
Xu et al. (Xu, et al. Gene 574.2: 352-358 (2015)) discloses Cyp3, which is deposited as UniProt V5W4C7 (deposited 2/19/2014):
MSSSSTNSTRPVVFMDVNIGETPAGRLKMELFSDIVPKTAENFRQLCTGEPQGYKGATFHRREAQTVTVGGDFLKGDGTGSFSIYGDKFPDENFKEKHTEPGLLSMANSGPNTNGCQFFVTTAKCDFLDGKHVVFGRVIDGMLTLRKIENVATGANNRPKLVVKIVGTCARRLPNVCAGPHRLIRSPRVW
This sequence is not markedly different than the claimed sequence because this sequence meets the claim limitations of claim 9. Any required activity is necessarily present because MPEP 2112.01(II) states: “"Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.”
This judicial exception is not integrated into a practical application because the claim is a composition claim that recites a peptide sequence. There is no integration present in the claim.
Step 2B:
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim is a composition claim that recites a peptide sequence. Similar to the integration analysis above, nothing is present in the claim that would amount to “significantly more”.
Consequently, clam 9 is rejected.
Regarding claim 10, claim 10 recites: “The AAV targeting peptide of claim 9, wherein the targeting peptide comprises at least 5 contiguous amino acids from the sequence TNSTRPV (SEQ ID NO: 15).”
Xu et al. (Xu, et al. Gene 574.2: 352-358 (2015)) discloses Cyp3, which is deposited as UniProt V5W4C7 (deposited 2/19/2014):
MSSSSTNSTRPVVFMDVNIGETPAGRLKMELFSDIVPKTAENFRQLCTGEPQGYKGATFHRREAQTVTVGGDFLKGDGTGSFSIYGDKFPDENFKEKHTEPGLLSMANSGPNTNGCQFFVTTAKCDFLDGKHVVFGRVIDGMLTLRKIENVATGANNRPKLVVKIVGTCARRLPNVCAGPHRLIRSPRVW
This sequence is not markedly different than the claimed sequence because this sequence meets the claim limitations of claim 10. Any required activity is necessarily present because MPEP 2112.01(II) states: “"Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.”
This judicial exception is not integrated into a practical application because the claim is a composition claim that recites a peptide sequence. There is no integration present in the claim.
Step 2B:
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim is a composition claim that recites a peptide sequence. Similar to the integration analysis above, nothing is present in the claim that would amount to “significantly more”.
Consequently, clam 10 is rejected.
Regarding claim 11, claim 11 recites: “The AAV targeting peptide of claim 9, wherein the targeting peptide comprises at least 6 contiguous amino acids from the sequence TNSTRPV (SEQ ID NO: 15).”
Xu et al. (Xu, et al. Gene 574.2: 352-358 (2015)) discloses Cyp3, which is deposited as UniProt V5W4C7 (deposited 2/19/2014):
MSSSSTNSTRPVVFMDVNIGETPAGRLKMELFSDIVPKTAENFRQLCTGEPQGYKGATFHRREAQTVTVGGDFLKGDGTGSFSIYGDKFPDENFKEKHTEPGLLSMANSGPNTNGCQFFVTTAKCDFLDGKHVVFGRVIDGMLTLRKIENVATGANNRPKLVVKIVGTCARRLPNVCAGPHRLIRSPRVW
This sequence is not markedly different than the claimed sequence because this sequence meets the claim limitations of claim 11. Any required activity is necessarily present because MPEP 2112.01(II) states: “"Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.”
This judicial exception is not integrated into a practical application because the claim is a composition claim that recites a peptide sequence. There is no integration present in the claim.
Step 2B:
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim is a composition claim that recites a peptide sequence. Similar to the integration analysis above, nothing is present in the claim that would amount to “significantly more”.
Consequently, clam 11 is rejected.
Regarding claim 12, claim 12 recites: “The AAV targeting peptide of claim 9, wherein the targeting peptide comprises TNSTRPV (SEQ ID NO: 15).”
Xu et al. (Xu, et al. Gene 574.2: 352-358 (2015)) discloses Cyp3, which is deposited as UniProt V5W4C7 (deposited 2/19/2014):
MSSSSTNSTRPVVFMDVNIGETPAGRLKMELFSDIVPKTAENFRQLCTGEPQGYKGATFHRREAQTVTVGGDFLKGDGTGSFSIYGDKFPDENFKEKHTEPGLLSMANSGPNTNGCQFFVTTAKCDFLDGKHVVFGRVIDGMLTLRKIENVATGANNRPKLVVKIVGTCARRLPNVCAGPHRLIRSPRVW
This sequence is not markedly different than the claimed sequence because this sequence meets the claim limitations of claim 12. Any required activity is necessarily present because MPEP 2112.01(II) states: “"Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.”
This judicial exception is not integrated into a practical application because the claim is a composition claim that recites a peptide sequence. There is no integration present in the claim.
Step 2B:
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim is a composition claim that recites a peptide sequence. Similar to the integration analysis above, nothing is present in the claim that would amount to “significantly more”.
Consequently, clam 12 is rejected.
Claim 15 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more. The claims recite peptide sequences found in nature.
Regarding claim 15, claim 15 recites: “A The AAV targeting peptide of claim 1, wherein the targeting peptide is conjugated to a nanoparticle, a second molecule, a viral capsid protein, or a combination thereof.”
Step 2A:
Xu et al. (Xu, Zhichao, et al. Gene 574.2: 352-358 (2015)) discloses Cyp3 of Ganoderma lucidum whose sequence is entered under UnitProt Assession Number V5W4C7 (deposited 2/19/2014) as described in claim 1:
MSSSSTNSTRPVVFMDVNIGETPAGRLKMELFSDIVPKTAENFRQLCTGEPQGYKGATFHRREAQTVTVGGDFLKGDGTGSFSIYGDKFPDENFKEKHTEPGLLSMANSGPNTNGCQFFVTTAKCDFLDGKHVVFGRVIDGMLTLRKIENVATGANNRPKLVVKIVGTCARRLPNVCAGPHRLIRSPRVW (emphasis added; Xu et al., page 354, Table 1).
This sequence is not markedly different than the claimed sequence because this sequence meets the claim limitations of claim 1. Any required activity is necessarily present because MPEP 2112.01(II) states: “"Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.”
This judicial exception is not integrated into a practical application because the claim is a composition claim that recites a peptide sequence. There is no integration present in the claim.
Step 2B:
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim is a composition claim that recites a peptide sequence. Similar to the integration analysis above, nothing is present in the claim that would amount to “significantly more”.
Regarding the compound to be conjugated to the peptide of Xu, Chuang et al. (Chuang, et al. FEMS microbiology letters 293.2: 205-213 (2009)) discloses that Ganoderma lucidum ubiquitinates proteins as part of the proteasome system:
“In this study, Cd induced expression of four TDFs similar to components of the ubiquitin–proteasome system. Northern blot analyses further validated Cd-inducible gene expression of TDF62A and 72A, exhibiting sequence similarity to genes encoding 20S proteasome and SKP1 protein, respectively. SKP1 is one of the components of the SCF ubiquitin ligase (Zhengetal., 2002). SCF complexes have been identified to mediate Cd tolerance in the yeasts Saccharomyces cerevisiae (Barbeyetal.,2005) and Saccharomyces pombe (Harrisonetal.,2005).” (Chuang, et al., page 210, col. 2, para. 2).
The ubiquitination system necessarily involves conjugation of ubiquitin to a target protein: “The selective degradation of many short-lived proteins in eukaryotic cells is carried out by the ubiquitin system. In this pathway, proteins are targeted for degradation by covalent ligation to ubiquitin, a highly conserved small protein. Ubiquitin-mediated degradation of regulatory proteins plays important roles in the control of numerous processes, including cell-cycle progression, signal transduction, transcriptional regulation, receptor down-regulation, and endocytosis.” (Hershko, et al., Abstract)
Because the resulting conjugate is naturally occurring as described above, claim 15 is rejected.
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 1, 9, 13, 15, 17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nonnenmacher et al. WO 2020/072683, published 4/9/2020.
Claim 1 recites: “An adeno-associated virus (AAV) targeting peptide comprising an amino acid sequence that comprises at least 4 contiguous amino acids from a sequence selected from the group consisting of GNNTRSV (SEQ ID NO: 13), GNNTRDT (SEQ ID NO: 14) and TNSTRPV (SEQ ID NO: 15).”
Nonnenmacher discloses SEQ ID NO: 143, DGTNSTTGW, a targeting peptide. This reads on the first four residues of Applicant SEQ ID NO: 15.
Consequently, claim 1 is anticipated by Nonnenmacher et al. and rejected.
Regarding claim 9, claim 1 is anticipated as described above. Claim 9 further recites the case wherein the targeting peptide comprises at least 4 contiguous amino acids from the sequence of TNSTRPV (SEQ ID NO: 15).
Nonnenmacher discloses SEQ ID NO: 143, DGTNSTTGW, a targeting peptide. This reads on the first four residues of Applicant SEQ ID NO: 15.
Consequently, claim 9 is anticipated by Nonnenmacher et al. and rejected.
Regarding claim 13, claim 1 is anticipated as described above. Claim 13 further recites the case wherein the AAV targeting peptide is part of an AAV.
Nonnenmacher discloses:” In one embodiment, the AAV particle of the disclosure comprises an AAV capsid with a targeting peptide insert, wherein the targeting peptide has an amino acid sequence as set forth in any of Table 2.” (Nonnenmacher et al., para. [0147]).
Consequently, claim 13 is anticipated by Nonnenmacher et al. and rejected.
Regarding claim 15, claim 1 is anticipated as described above. Claim 15 further recites the case wherein the peptide is conjugated to a nanoparticle, a second molecule, a viral capsid protein, or a combination thereof.
Nonnenmacher discloses: “Targeting peptides may be stand-alone peptides or may be inserted into or conjugated to a parent sequence. In one embodiment, the targeting peptides are inserted into the capsid protein of an AAV particle.” (Nonnenmacher et al., para. [0155]).
Consequently, claim 13 is anticipated by Nonnenmacher et al. and rejected.
Regarding claim 17, claim 1 is anticipated as described above. Claim 17 further recites an adeno-associated virus (AAV) capsid protein comprising an AAV targeting peptide of claim 1.
Nonnenmacher discloses:” In one embodiment, the AAV particle of the disclosure comprises an AAV capsid with a targeting peptide insert, wherein the targeting peptide has an amino acid sequence as set forth in any of Table 2.” (Nonnenmacher et al., para. [0147]).
Consequently, claim 17 is anticipated by Nonnenmacher et al. and rejected.
Claims 2-4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by UniProt Accession No. V8NWD4_OPHHA (Accessed 6/1/2026, deposited 2/19/2014).
Regarding claim 2, claim 2 recites: “The AAV targeting peptide of claim 1, wherein the targeting peptide comprises at least 5 contiguous amino acids from the sequence of GNNTRSV (SEQ ID NO: 13).”
UniProt Accession No. V8NWD4_OPHHA discloses the following sequence (Deposited 2/19/2014):
MQNQPVGTPSSGREGQPSEMLKDLILRWFLETQIVLLLQDGRLPDWFHGFLSRQEAEMLLENKEFGCFLIRLNEKAFGYILSYRGKDRCRHFVISCHRSGRYLVSGDSQTHAQLAELISYYQRSPSADAPTLSRNPSADLLVTRSHFTNQPGHPRIPLQKEQKSLFKEPQNAKEDPDEAPPIPDRSRLLESLSLEEEVGDEGTIYSAVKKPPLDKKSLGKSKEGGRNFGDTKAKEPVGPGQGLSSPCQRKTGTMFGLAKRSDTPFTIKVNPAERAQTGTIYSRIAFDQPKTFWIPAEPPSYQSTCPSSKKSAVPNYPPLKLSPTLPNKSKYSVAFHGSPLGNNTRSVGNKEHGQLNQPKSLFELPKDHTGEKIFQLKNQPSALWADNTTNTQESFRWAKSIFLGSEKPPKASLTRSKGSYDQISAKFGHVSKIQINPESPYEKITDPYSHCSSATSQAASLEDPYEQIPYLPGKRIEGKVTPKSEKPRKFLFTDKKAKS
Consequently, claim 2 is anticipated by UniProt Accession No. V8NWD4_OPHHA claim and rejected.
Regarding claim 3, claim 3 recites: “The AAV targeting peptide of claim 1, wherein the targeting peptide comprises at least contiguous amino acids from the sequence of GNNTRSV (SEQ ID NO: 13).”
UniProt Accession No. V8NWD4_OPHHA discloses the following sequence (Deposited 2/19/2014):
MQNQPVGTPSSGREGQPSEMLKDLILRWFLETQIVLLLQDGRLPDWFHGFLSRQEAEMLLENKEFGCFLIRLNEKAFGYILSYRGKDRCRHFVISCHRSGRYLVSGDSQTHAQLAELISYYQRSPSADAPTLSRNPSADLLVTRSHFTNQPGHPRIPLQKEQKSLFKEPQNAKEDPDEAPPIPDRSRLLESLSLEEEVGDEGTIYSAVKKPPLDKKSLGKSKEGGRNFGDTKAKEPVGPGQGLSSPCQRKTGTMFGLAKRSDTPFTIKVNPAERAQTGTIYSRIAFDQPKTFWIPAEPPSYQSTCPSSKKSAVPNYPPLKLSPTLPNKSKYSVAFHGSPLGNNTRSVGNKEHGQLNQPKSLFELPKDHTGEKIFQLKNQPSALWADNTTNTQESFRWAKSIFLGSEKPPKASLTRSKGSYDQISAKFGHVSKIQINPESPYEKITDPYSHCSSATSQAASLEDPYEQIPYLPGKRIEGKVTPKSEKPRKFLFTDKKAKS
Consequently, claim 3 is anticipated by UniProt Accession No. V8NWD4_OPHHA claim and rejected.
Regarding claim 4, claim 4 recites: “The AAV targeting peptide of claim 1, wherein the targeting peptide comprises GNNTRSV (SEQ ID NO: 13).”
UniProt Accession No. V8NWD4_OPHHA discloses the following sequence (Deposited 2/19/2014):
MQNQPVGTPSSGREGQPSEMLKDLILRWFLETQIVLLLQDGRLPDWFHGFLSRQEAEMLLENKEFGCFLIRLNEKAFGYILSYRGKDRCRHFVISCHRSGRYLVSGDSQTHAQLAELISYYQRSPSADAPTLSRNPSADLLVTRSHFTNQPGHPRIPLQKEQKSLFKEPQNAKEDPDEAPPIPDRSRLLESLSLEEEVGDEGTIYSAVKKPPLDKKSLGKSKEGGRNFGDTKAKEPVGPGQGLSSPCQRKTGTMFGLAKRSDTPFTIKVNPAERAQTGTIYSRIAFDQPKTFWIPAEPPSYQSTCPSSKKSAVPNYPPLKLSPTLPNKSKYSVAFHGSPLGNNTRSVGNKEHGQLNQPKSLFELPKDHTGEKIFQLKNQPSALWADNTTNTQESFRWAKSIFLGSEKPPKASLTRSKGSYDQISAKFGHVSKIQINPESPYEKITDPYSHCSSATSQAASLEDPYEQIPYLPGKRIEGKVTPKSEKPRKFLFTDKKAKS
Consequently, claim 4 is anticipated by UniProt Accession No. V8NWD4_OPHHA claim and rejected.
Claims 5-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by UniProt Accession No. R0KK08_EXST2 (accessed 6/1/2026, deposited 6/23/2013).
Regarding claim 5, claim 5 recites: “The AAV targeting peptide of claim 1, wherein the targeting peptide comprises at least 4 contiguous amino acids from the sequence GNNTRDT (SEQ ID NO: 14).”
UniProt Accession No. R0KK08_EXST2 discloses:
MKTLLITLSALTAAVTAASSSGCGKSLPDNVHLGESVNLTIKSESGATPRGYRLHIPPSYEQNTELPLILSFHGRGKDAKFQEALSQFSNASYGFEGIAVYPEGVPNKKGTQQFEGDPDSPKSISDVTFTLELLDHLESTYCIDTSRIYANGKSNGGGFTGILACDAKATKRIAAFAPVSGAFYLDADQQPPPCNPSRKPIPFMEFHGYPDSTIRYQGGNNTRDTASTSDIVTYVNDWARRDGFEPAANKTTHLCSGKKAVTRHSWDDVVVDYNYTNIKHDWPSSFPNGDTDTLLTCEDAEATPIILEWFKKWTI
Consequently, claim 5 is anticipated by UniProt Accession No. R0KK08_EXST2 claim and rejected.
Regarding claim 6, claim 6 recites: “The AAV targeting peptide of claim 5, wherein the targeting peptide comprises at least 5 contiguous amino acids from the sequence GNNTRDT (SEQ ID NO: 14).”
UniProt Accession No. R0KK08_EXST2 discloses:
MKTLLITLSALTAAVTAASSSGCGKSLPDNVHLGESVNLTIKSESGATPRGYRLHIPPSYEQNTELPLILSFHGRGKDAKFQEALSQFSNASYGFEGIAVYPEGVPNKKGTQQFEGDPDSPKSISDVTFTLELLDHLESTYCIDTSRIYANGKSNGGGFTGILACDAKATKRIAAFAPVSGAFYLDADQQPPPCNPSRKPIPFMEFHGYPDSTIRYQGGNNTRDTASTSDIVTYVNDWARRDGFEPAANKTTHLCSGKKAVTRHSWDDVVVDYNYTNIKHDWPSSFPNGDTDTLLTCEDAEATPIILEWFKKWTI
Consequently, claim 6 is anticipated by UniProt Accession No. R0KK08_EXST2 claim and rejected.
Regarding claim 7, claim 7 recites: “The AAV targeting peptide of claim 5, wherein the targeting peptide comprises at least 6 contiguous amino acids from the sequence GNNTRDT (SEQ ID NO: 14).”
UniProt Accession No. R0KK08_EXST2 discloses:
MKTLLITLSALTAAVTAASSSGCGKSLPDNVHLGESVNLTIKSESGATPRGYRLHIPPSYEQNTELPLILSFHGRGKDAKFQEALSQFSNASYGFEGIAVYPEGVPNKKGTQQFEGDPDSPKSISDVTFTLELLDHLESTYCIDTSRIYANGKSNGGGFTGILACDAKATKRIAAFAPVSGAFYLDADQQPPPCNPSRKPIPFMEFHGYPDSTIRYQGGNNTRDTASTSDIVTYVNDWARRDGFEPAANKTTHLCSGKKAVTRHSWDDVVVDYNYTNIKHDWPSSFPNGDTDTLLTCEDAEATPIILEWFKKWTI
Consequently, claim 7 is anticipated by UniProt Accession No. R0KK08_EXST2 claim and rejected.
Regarding claim 8, claim 8 recites: “The AAV targeting peptide of claim 5, wherein the targeting peptide comprises GNNTRDT (SEQ ID NO: 14).”
UniProt Accession No. R0KK08_EXST2 discloses:
MKTLLITLSALTAAVTAASSSGCGKSLPDNVHLGESVNLTIKSESGATPRGYRLHIPPSYEQNTELPLILSFHGRGKDAKFQEALSQFSNASYGFEGIAVYPEGVPNKKGTQQFEGDPDSPKSISDVTFTLELLDHLESTYCIDTSRIYANGKSNGGGFTGILACDAKATKRIAAFAPVSGAFYLDADQQPPPCNPSRKPIPFMEFHGYPDSTIRYQGGNNTRDTASTSDIVTYVNDWARRDGFEPAANKTTHLCSGKKAVTRHSWDDVVVDYNYTNIKHDWPSSFPNGDTDTLLTCEDAEATPIILEWFKKWTI
Consequently, claim 8 is anticipated by UniProt Accession No. R0KK08_EXST2 claim and rejected.
Claims 9-12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Xu et al. (Xu, et al. Gene 574.2: 352-358 (2015)) whose sequence is deposited as UniProt V5W4C7 (deposited 2/19/2014):
Regarding claim 9, claim 9 recites: “The AAV targeting peptide of claim 1, wherein the targeting peptide comprises at least 4 contiguous amino acids from the sequence TNSTRPV (SEQ ID NO: 15).”
Xu et al. (Xu, et al. Gene 574.2: 352-358 (2015)) discloses Cyp3 (Xu et al., page 353, Table 1), which is deposited as UniProt V5W4C7 (deposited 2/19/2014):
MSSSSTNSTRPVVFMDVNIGETPAGRLKMELFSDIVPKTAENFRQLCTGEPQGYKGATFHRREAQTVTVGGDFLKGDGTGSFSIYGDKFPDENFKEKHTEPGLLSMANSGPNTNGCQFFVTTAKCDFLDGKHVVFGRVIDGMLTLRKIENVATGANNRPKLVVKIVGTCARRLPNVCAGPHRLIRSPRVW
Consequently, claim 9 is anticipated by Xu et al. and UniProt V5W4C7 and rejected.
Regarding claim 10, claim 10 recites: “The AAV targeting peptide of claim 9, wherein the targeting peptide comprises at least 5 contiguous amino acids from the sequence TNSTRPV (SEQ ID NO: 15).”
Xu et al. (Xu, et al. Gene 574.2: 352-358 (2015)) discloses Cyp3 (Xu et al., page 353, Table 1), which is deposited as UniProt V5W4C7 (deposited 2/19/2014):
MSSSSTNSTRPVVFMDVNIGETPAGRLKMELFSDIVPKTAENFRQLCTGEPQGYKGATFHRREAQTVTVGGDFLKGDGTGSFSIYGDKFPDENFKEKHTEPGLLSMANSGPNTNGCQFFVTTAKCDFLDGKHVVFGRVIDGMLTLRKIENVATGANNRPKLVVKIVGTCARRLPNVCAGPHRLIRSPRVW
Consequently, claim 10 is anticipated by Xu et al. and UniProt V5W4C7 and rejected.
Regarding claim 11, claim 11 recites: “The AAV targeting peptide of claim 9, wherein the targeting peptide comprises at least 6 contiguous amino acids from the sequence TNSTRPV (SEQ ID NO: 15).”
Xu et al. (Xu, et al. Gene 574.2: 352-358 (2015)) discloses Cyp3 (Xu et al., page 353, Table 1), which is deposited as UniProt V5W4C7 (deposited 2/19/2014):
MSSSSTNSTRPVVFMDVNIGETPAGRLKMELFSDIVPKTAENFRQLCTGEPQGYKGATFHRREAQTVTVGGDFLKGDGTGSFSIYGDKFPDENFKEKHTEPGLLSMANSGPNTNGCQFFVTTAKCDFLDGKHVVFGRVIDGMLTLRKIENVATGANNRPKLVVKIVGTCARRLPNVCAGPHRLIRSPRVW
Consequently, claim 11 is anticipated by Xu et al. and UniProt V5W4C7 and rejected.
Regarding claim 12, claim 12 recites: “The AAV targeting peptide of claim 9, wherein the targeting peptide comprises TNSTRPV (SEQ ID NO: 15).”
Xu et al. (Xu, et al. Gene 574.2: 352-358 (2015)) discloses Cyp3 (Xu et al., page 353, Table 1), which is deposited as UniProt V5W4C7 (deposited 2/19/2014):
MSSSSTNSTRPVVFMDVNIGETPAGRLKMELFSDIVPKTAENFRQLCTGEPQGYKGATFHRREAQTVTVGGDFLKGDGTGSFSIYGDKFPDENFKEKHTEPGLLSMANSGPNTNGCQFFVTTAKCDFLDGKHVVFGRVIDGMLTLRKIENVATGANNRPKLVVKIVGTCARRLPNVCAGPHRLIRSPRVW
Consequently, claim 12 is anticipated by Xu et al. and UniProt V5W4C7 and rejected.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 2, 5, 13, 15, and 17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 15, 17, and 18 of copending Application No. 18/692,014 (reference application) in view of Henikoff, et al. (Henikoff, et al. Proceedings of the national academy of sciences 89.22: 10915-10919 (1992)). Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 1, claim 1 recites: “An adeno-associated virus (AAV) targeting peptide comprising an amino acid sequence that comprises at least 4 contiguous amino acids from a sequence selected from the group consisting of GNNTRSV (SEQ ID NO: 13), GNNTRDT (SEQ ID NO: 14) and TNSTRPV (SEQ ID NO: 15).”
Claim 1 of the ‘014 application discloses: “An adeno-associated virus (AAV) targeting peptide comprising an amino acid sequence that comprises at least 4 contiguous amino acids from a sequence selected from the group consisting of PHEGSSR (SEQ ID NO: 169), LNNTKTT (SEQ ID NO: 237), SNLARNV (SEQ ID NO: 274) and TNINTKIPL (SEQ ID NO: 390).”
SEQ ID NO: 237 has four contiguous amino acids NNTK. Lysine to arginine is considered a conservative mutation as shown by Henikoff:
PNG
media_image1.png
390
783
media_image1.png
Greyscale
(Henikoff et al., page 10917, Fig. 2)
It would have been obvious to a person of ordinary skill in the art before the effective filing date to alter the contiguous sequence of the ‘014 application as suggested by Henikoff to arrive at the claimed invention.
A person of ordinary skill in the would make such a substitution to probe for increased activity or slightly alter the properties at that location in the peptide. A person of ordinary skill in the would have a reasonable expectation of success because this is considered a conservative substation as shown by Henikoff.
Consequently, claim 1 is obvious over the ‘014 application in view of Henikoff and provisionally rejected.
Regarding claim 2, claim 1 is obvious as described above. Claim 2 further recites the case wherein the targeting peptide comprises at least 5 contiguous amino acids from the sequence of GNNTRSV (SEQ ID NO: 13).
SEQ ID NO: 237 has five contiguous amino acids NNTKT. Lysine to arginine is obvious as described above. Threonine to serine is also a conservative amino acid substitution as described by Henikoff above.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to alter the contiguous sequence of the ‘014 application as suggested by Henikoff to arrive at the claimed invention.
A person of ordinary skill in the would make such a substitution to probe for increased activity or slightly alter the properties at that location in the peptide. A person of ordinary skill in the would have a reasonable expectation of success because this is considered a conservative substation as shown by Henikoff
Consequently, claim 2 is obvious over the ‘014 application in view of Henikoff and provisionally rejected.
Regarding claim 5, claim 5 recites: “The targeting peptide of claim 1, wherein the targeting peptide comprises at least 4 contiguous amino acids from the sequence GNNTRDT (SEQ ID NO: 14).
SEQ ID NO: 237 has four contiguous amino acids NNTK. Lysine to arginine is considered a conservative mutation as shown by Henikoff:
PNG
media_image1.png
390
783
media_image1.png
Greyscale
(Henikoff et al., page 10917, Fig. 2)
It would have been obvious to a person of ordinary skill in the art before the effective filing date to alter the contiguous sequence of the ‘014 application as suggested by Henikoff to arrive at the claimed invention.
A person of ordinary skill in the would make such a substitution to probe for increased activity or slightly alter the properties at that location in the peptide. A person of ordinary skill in the would have a reasonable expectation of success because this is considered a conservative substation as shown by Henikoff.
Consequently, claim 5 is obvious over the ‘014 application in view of Henikoff and provisionally rejected.
Regarding claim 13, claim 1 is obvious as described above. Claim 13 recites: “The AAV targeting peptide of claim 1, wherein the targeting AAV peptide is part of an AAV.
Claim 15 of the ‘014 application discloses the case wherein the AAV targeting peptide is part of an AAV.
Consequently, claim 13 is obvious over the ‘014 application in view of Henikoff and provisionally rejected.
Regarding claim 15, claim 1 is obvious as described above. Claim 15 further recites the case wherein the AAV targeting peptide is conjugated to a nanoparticle, a second molecule, a viral capsid protein, or a combination thereof.
Claim 17 of the ‘014 application recites the case wherein the AAV targeting peptide is conjugated to a nanoparticle, a second molecule, a viral capsid protein, or a combination thereof.
Consequently, claim 15 is obvious over the ‘014 application in view of Henikoff and provisionally rejected.
Regarding claim 17, claim 1 is obvious as described above. Claim 17 further recites an adeno-associated virus (AAV) capsid protein comprising an AAV targeting peptide of claim 1.
Claim 18 of the ‘014 application recites an adeno-associated virus (AAV) capsid protein comprising an AAV targeting peptide of claim 1.
Consequently, claim 17 is obvious over the ‘014 application in view of Henikoff and provisionally rejected.
Conclusion
No claim is allowed
Claims 17-21 are objected to.
Claims 1-13, 15, and 17-21 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to David Paul Bowles whose telephone number is (571)272-0919. The examiner can normally be reached Monday-Friday 8:30-5:00.
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, Lianko Garyu can be reached on (571) 270-7367. 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.
/DAVID PAUL BOWLES/ Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654
Prosecution Insights