DETAILED CORRESPONDENCE
Status of the Application
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-2, 7-8, 10, 12-13, 18-19, 22, 24-25, 33-34, 37-38, 41-43 and 46-47 are pending in this application.
Election
Applicant’s election of
Group I, claims 1-2, 7-8, 10, 12-13, 18-19, 22, 24-25, 33-34, 37-38, 41-42 and 46-47, drawn to the technical feature of a fusion protein comprising a WW-containing domain, a transmembrane domain and an extracellular domain, an isolated nucleic acid encoding the fusion protein, a WAEV comprising a lipid bilayer and the fusion protein, a WAEV-producing cell comprising the isolated nucleic acid, a WAEV-producing cell comprising a recombinant expression construct encoding the fusion protein under the control of a heterologous promoter, and a kit comprising the fusion protein,
Species A1) the WW-containing domain is the NEDD4 E3 ligase domain ITCH, including an ITCH comprising a sequence having at least 95% identity to SEQ ID NO: 1 or a sequence comprising SEQ ID NO: 1,
Species B1) the transmembrane domain is a M2 transmembrane domain, including an M2 transmembrane domain comprising a sequence having at least 95% identity to SEQ ID NO: 9 or comprises a sequence comprising SEQ ID NO: 9,
Species C1) the extracellular domain is an influenza antigen domain comprising M2 extracellular domain, or comprises a sequence having at least 95% identity to SEQ ID NO: 8 or comprises a sequence comprising SEQ ID NO: 8, and
Species D1) the fusion protein comprises a sequence having at least 95% identity to SEQ ID NO: 61, or comprises the sequence of SEQ ID NO: 61, or consists of the sequence of SEQ ID NO: 61
in the reply filed 01/06/2026 is acknowledged.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claim 43 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/06/2026.
The elected species of D1) the fusion protein comprises a sequence having at least 95% identity to SEQ ID NO: 61, or comprises the sequence of SEQ ID NO: 61, or consists of the sequence of SEQ ID NO: 61 is free of the prior art of record, and in accordance with MPEP 803.02.III.A, the search and examination has been extended to the non-elected species of D2) the fusion protein comprises a sequence having at least 95% identity to SEQ ID NO: 62, or comprises the sequence of SEQ ID NO: 62, or consists of the sequence of SEQ ID NO: 62. In view of the extension of the search and examination to species D2), the requirement for election between the species of D1) and D2) is withdrawn.
Claims 1-2, 7-8, 10, 12-13, 18-19, 22, 24-25, 33-34, 37-38, 41-42 and 46-47 are being examined on the merits only to the extent they read on the elected subject matter.
Priority
The instant application is a national stage filing under 35 U.S.C. 371 of international application PCT/US2021/055203 filed 10/15/2021, which claims domestic priority to U.S. Provisional Application No. 63/093,101 filed 10/16/2020.
Information Disclosure Statement
The Information Disclosure Statements (IDSs) submitted on 07/14/2023, 12/27/2023, 12/31/2024 and 01/06/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDSs have been considered by the examiner.
Applicant’s submission filed 12/31/2024 of “Statement Filed Pursuant to the Duty of Disclosure Under 37 CFR 1.56, 1.97 and 1.98” has been crossed out as it is not a Form PTO-892. Applicant should cite the documents referenced in the submission corresponding to U.S. Application 18/845704, PCT/US2023/064262, EP 21821526.7, EP 21881163.6, and EP 21881160.2 on an IDS form PTO/SB/08 if Applicant would like said documents to be considered.
Applicant’s submission filed 01/06/2024 of “Statement Filed Pursuant to the Duty of Disclosure Under 37 CFR 1.56, 1.97 and 1.98” has been crossed out as it is not a Form PTO-892. Applicant should cite the documents referenced in the submission corresponding to PCT/US2023/064262, and EP 21881181.8 on an IDS form PTO/SB/08 if Applicant would like said documents to be considered.
Objections to Specification
The disclosure is objected to because of the following informalities.
The use of the terms NANOSIGHT, OPTIPREP, CHARLES RIVER, PROIMMUNE, SIGMA, and R&D SYSTEMS, which are trade names or marks used in commerce, have been noted in this application in paragraphs 0029, 0033-0035, 0037, 00130-00132. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
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.
Appropriate correction is required.
Objections to Drawings
The drawings are objected to because Figures 1, 2, 8A, and 13 display sequences. Pursuant to 37 CFR 1.83(a), sequences that are included in the "Sequence Listing XML" should not be duplicated in the drawings (see MPEP 2412.06).
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action.
The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 25 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitation of the base claim and any intervening claims.
Claim 33 is objected to for the phrase “An isolated nucleic acid encoding a fusion protein of claim 1”. In the interest of improving claim form, Applicant should consider an amendment to recite “An isolated nucleic acid comprising a nucleotide sequence encoding the fusion protein of claim 1”.
Claim 46 is objected to for the typo in the phrase “A kit comprising a the fusion protein of claim 1”. In the interest of improving claim form, Applicant should consider an amendment to recite “A kit comprising the fusion protein of claim 1”.
Claim 47 is objected to for the typo in the phrase “wherein the fusion protein is furth bound”. In the interest of improving claim form, Applicant should consider an amendment to recite “wherein the fusion protein is further bound”.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 12 and 34 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention. Claim 12 recites the limitation “the hemagglutinin (H2) transmembrane domain” in line 2. There is insufficient antecedent basis for this claim.
Claim 34 is indefinite for the phrase “wherein the isolated nucleic acid is operably linked to a promoter … and/or wherein the isolated nucleic acid comprises at least one additional regulator sequence”. The limitations of a promoter further limited by the Markush group of promoters and the additional regulator sequence are recited in the alternative, and as a result the claims encompass the limitation “the isolated nucleic acid comprises at least one additional regulator sequence” without requiring the isolated nucleic acid to have a first regulator sequence.
Claim Rejections - 35 USC § 112(a)
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.
Claim Interpretation: the claims are drawn to a fusion protein comprising (a) a WW-containing domain, (b) a transmembrane domain, and (c) an extracellular domain. The terms “WW-containing domain” and “WW domain” in the instant specification at [para 0063] are stated to be used interchangeably, and are defined as “a protein having two basic residues at the C-terminus that mediate protein-protein interactions with short proline-rich or proline-containing motifs”, and gives examples of the basic resides to be histidine, arginine, and/or lysine. As a WW-containing domain is not specifically defined in terms of structure, under the broadest reasonable interpretation it can be considered to be any peptide containing any combination of two basic residues at the C-terminus. Therefore, with the exception of the combination of any two basic residues at the C-terminus, component (a) of the claimed fusion protein is considered structurally unlimited. As such, the claimed fusion protein is drawn to a genus of polypeptides that is considered widely variable with respect to structure.
A. Claims 1-2, 12-13, 18-19, 22, 24, 33-34, 37-38, 41-42 and 46-47 are rejected under 35 U.S.C. 112(a) 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 at the time the application was filed, had possession of the claimed invention.
MPEP § 2163.II.A.3.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”.
For claims drawn to a genus, MPEP § 2163.II.A.3.(a).ii) states 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.
According to § MPEP 2163.II.A.3.(a).ii), “[s]atisfactory disclosure of a ‘representative number’ depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. 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…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.’”
The factors considered in the Written Description requirement are (1) level of skill and knowledge in the art, (2) partial structure, (3) physical and/or chemical properties, (4) functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the (5) method of making the claimed invention. According to MPEP § 2163, “Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient."
The claims recite (in relevant part) a genus of fusion proteins comprising (a) a WW-containing domain, (b) a transmembrane domain, and (c) an extracellular domain. As stated above, with the exception of the combination of any two basic residues at the C-terminus, the remaining amino acid sequence the WW-containing domain of part (a), and the genus of fusion proteins is considered structurally unlimited. In this case, the genus of recited fusion proteins encompasses species that are considered widely variant with respect to structure.
The specification discloses the following representative species of the genus of fusion proteins: Fusion 1 corresponding to SEQ ID NO: 61 and Fusion 2 corresponding to SEQ ID NO: 62.
Regarding the level of skill and knowledge in the art of amino acid modification, the reference of Singh et al. (Curr. Protein Pept. Sci. 18:1-11, 2017; cited on the attached Form PTO-892) reviews various protein engineering methods and discloses that despite the availability of an ever-growing database of protein structures and highly sophisticated computational algorithms, protein engineering is still limited by the incomplete understanding of protein functions, folding, flexibility, and conformational changes (see p. 7, column 1, top). Also, the unpredictability associated with residue substitution is exemplified by the reference of Zhang et al. (Structure 26:1474-1485, 2018; cited on the attached Form PTO-892), which discloses that even a substitution of a surface residue that was predicted to be benign caused significant structural changes and unexpected effects on the function of a polypeptide (p. 1475, column 1).
In view of the high level of unpredictability in the art of amino acid modification, because the genus fusion proteins is widely variant with respect to structure, and the specification discloses the actual reduction to practice of only two representative species among a widely variant genus, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus, and thus, that the applicant was not in possession of the recited genus of fusion proteins. The claimed subject matter is not supported by an adequate written description because a representative number of species has not been described.
B. Claims 1-2, 12-13, 18-19, 22, 24, 33-34, 37-38, 41-42 and 46-47 are rejected under 35 U.S.C. 112(a) because the specification, while being enabling for a fusion protein comprising the amino acid sequence of SEQ ID NOs: 61-62, does not reasonably provide enablement for fusion proteins as encompassed by the claims. 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 and/or use the invention commensurate in scope with these claims.
“The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue.” In re Angstadt, 537 F.2d 498, 504, 190 USPQ 214, 219 (CCPA 1976). Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)) as follows: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. See MPEP § 2164.01(a). The Factors considered to be most relevant to the instant rejection are addressed in detail below.
The nature of the invention: According to the specification at para 0004, “The present disclosure relates […] to novel extracellular vesicles (EVs) which contain WW-domain containing proteins with extracellular domains (WW-domain- Activated Extracellular Vesicles, or WAEVs). Extracellular domains of interest can be presented on the surface of the EVs through the introduction of WW-domain containing proteins that are fused to a transmembrane domain associated […] with the extracellular domain […] WAEVS can be used to deliver and present viral or bacterial antigens useful for vaccine development; to display homing molecules for targeted delivery of therapeutic molecules to specific cells or tissues; and for packaging and delivery of therapeutic molecules, for example through interactions with the WW domains”. The object of the invention is therefore to provide a novel vehicle for vaccine development or targeted delivery of therapeutic molecules comprising WAEVs consisting of WW-domain containing fusion proteins.
The breadth of the claims: The claims recite a fusion protein comprising (a) a WW-containing domain, (b) a transmembrane domain, and (c) an extracellular domain. As stated above, with the exception of the combination of any two basic residues at the C-terminus of the WW-containing domain of part (a), the remaining the remaining amino acid sequence of the fusion protein is unlimited.
The state of the prior art; The level of one of ordinary skill; and The level of predictability in the art: According to MPEP 2164.03, “…what is known in the art provides evidence as to the question of predictability” and “[I]f one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains, then there is lack of predictability in the art.”
As noted above, other than the combination of any two basic residues at the C-terminus in the WW-containing domain of part (a) of the fusion protein, the amino acid sequence of the recited fusion protein is unlimited. The reference of Singh (supra) reviews various protein engineering methods and discloses that despite the availability of an ever-growing database of protein structures and highly sophisticated computational algorithms, protein engineering is still limited by the incomplete understanding of protein functions, folding, flexibility, and conformational changes (see p. 7, column 1, top).
The unpredictability associated with amino acid modification is exemplified by the reference of Zhang (supra) which discloses that even a mutation that was predicted to be benign caused significant structural changes and unexpected effects on the function of a polypeptide (p. 1475, column 1).
As such, one of skill in the art would recognize a high level of unpredictability that all fusion proteins as encompassed by the claims would maintain the desired activity/utility of mediating protein-protein interactions with short proline-rich or proline-containing motifs.
The amount of direction provided by the inventor and The existence of working examples: The specification discloses the following working examples of the recited fusion protein: Fusion 1 corresponding to SEQ ID NO: 61 and Fusion 2 corresponding to SEQ ID NO: 62. Other than these working examples, the specification fails to disclose any other fusion protein. Also, the specification fails to provide guidance for using those fusion proteins that are non-functional or do not display the desired activity of mediating protein-protein interactions with short proline-rich or proline-containing motifs.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure: While methods of modifying the amino acid sequence of a polypeptide were known at the time of the invention, it was not routine in the art to make and determine a use for all fusion proteins as recited by the claims.
In view of the overly broad scope of the claims, the lack of guidance and working examples provided in the specification, the high level of unpredictability, and the state of the prior art, undue experimentation would be necessary for a skilled artisan to make and use the entire scope of the claimed invention. Applicants have not provided sufficient guidance to enable one of ordinary skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims. The scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without sufficient guidance, determination of having the desired biological characteristics is unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988).
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-2, 24, 33-34, 37-38, 41-42 and 47 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 2014/0005126 A1 (cited on the IDS filed 07/14/2023; herein referred to as Ullman) and evidentiary reference Tiller et al. (Annu Rev Biomed Eng, 2015, 17:191; cited on the attached Form PTO-892; herein referred to as Tiller)
The claims are drawn to a fusion protein comprising:
a WW-containing domain;
a transmembrane domain; and
an extracellular domain.
Ullman relates to modified WW-domain peptides that bind desired targeted ligands [abstract].
Regarding claims 1-2, Ullman discloses a modified WW domain peptide produced by recombinant DNA technology and standard expression and purification procedure [para 0084] that can have an attached second molecules such as an antibody [para 0086], wherein the modified WW domain peptide may be grown in a fusion with another protein [para 0084], and wherein antibodies are understood to contain both extracellular and transmembrane domains as evidenced by Tiller [Figure 2], and wherein the fusion protein does not comprise an arrestin domain containing protein 1 (AARDC1).
Regarding claim 24, the term “signal peptide” is not defined in the instant specification. The specification does define a “signal” or a “signal tag” to “refer [to] a molecule (e.g., peptide, nucleic acid, other moiety) associated with a subject molecule to identify the subject molecule during use” [para 0058]. Ullman discloses to aid in purifying peptides of the invention, the invention may include a purification sequence such as a His-tag [para 0084], which is considered to be a peptide molecule used to identify the subject molecule.
Regarding claim 33, Ullman discloses the modified WW domain peptide can be produced by standard expression and purification procedure that includes nucleic acid molecules encoding the peptide, such as expression vectors comprising the nucleic acid [para 0084], and that the nucleic acid may be isolated [para 0081].
Regarding claim 34, Ullman discloses the DNA encoding the relevant peptide can be inserted into a suitable expression vector (e.g. pGem) where it is operably linked to appropriate expression sequences and transformed into a suitable host cell for protein expression [para 0084], which is considered to correspond to a nucleic acid operably linked to an inducible promoter.
Regarding claim 37, Ullman discloses the modified WW domain peptide as described in the rejection of claim 1 may be mixed with a population of liposomes such as a lipid vesicle [para 0101], which corresponds to an extracellular vesicle comprising a fusion peptide and a lipid bilayer.
Regarding claim 38, the liposome-encapsulated modified WW domain peptide as described in the rejection of claim 37 is considered to not comprise any of CD63, CD81, CD9 and PTGFRN.
Regarding claims 41-42, Ullman discloses the modified WW domain peptide described in the rejection of claim 1 can be encoded by nucleic acids as described in the rejection of claim 33, inserted into a suitable expression vector such as a pGEM vector, and transformed into a suitable host cell for protein expression, wherein suitable host cells include bacteria, fungal cells and cells of higher eukaryotic origin [para 0084], wherein pGEM vectors are understood to contain heterologous promoters that drive expression of an encoded protein. As the phrase “A WAEV-producing cell” does not impart any structural characteristics on the cell of claims 41-42, the cell of Ullman satisfies all of the structural limitations of claims 41-42.
Regarding claim 47, the phrase “the fusion protein is further bound to a SCAMP3 protein or a variant thereof” is considered an intended use of the claimed fusion protein (see MPEP 2111.02.II), and does not provide any structural limitations on the claimed fusion protein. As the fusion protein of Ullman is encompassed by the structural limitations of claim 47, it is considered to satisfy the limitations of claim 47. Considering an alternative interpretation that the recited phrase limits the fusion protein to have a structure capable of binding SCAMP3, as the fusion protein of Ullman is encompassed by the structural limitations of claim 47, it is considered to have the capability of binding SCAMP3, as the function of a protein is considered to be inherent to its structure (see MPEP 2112).
For these reasons, Ulllman anticipates claims 1-2, 24, 33-34, 37-38, 41-42 and 47.
Claim Rejections - 35 USC § 103
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 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 7-8 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Ullman as applied to claims 1-2, 24, 33-34, 37-38, 41-42 and 47 above, and further in view of UniProt Accession No. Q96J02 (16 pages, 09/18/2019; cited on the attached Form PTO-892; herein referred to as UNI1).
Claim 7 is drawn to the fusion protein of claim 1, wherein the WW-containing domain is a NEDD4 E3 ligase domain.
Claim 8 is drawn to the fusion protein of claim 7, wherein the NEDD4 E3 ligase is ITCH as elected.
Claim 10 is drawn to the fusion protein of claim 1, wherein the WW-containing domain comprises a sequence having at least 95% identity to the sequence of SEQ ID NO: 1 or a sequence comprising SEQ ID NO: 1.
The teachings of Ullman as applied to claims 1-2, 24, 33-34, 37-38, 41-42 and 47 are discussed above. Ullman does not teach a NEDD3 E3 ligase domain as the WW-containing domain.
Regarding claims 7-8 and 10, UNI1 discloses an ITCH protein that is an E3 ubiquitin-protein ligase [p 1], wherein ITCH contains multiple WW domains [p 14], and shares 100% sequence identity with SEQ ID NO: 1 [see Appendix A].
In view of UNI1, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to modify the fusion protein of Ullman by replacing the WW-domain peptide with the peptide of UNI1, since the simple substitution of known element for another results in a predictable result. One of ordinary skill in the art would have recognized that the WW-domain peptide of Ullman and the ITCH protein of UNI1 are both WW-domain containing peptides, and as such both are capable of being incorporated into fusion proteins as described by Ullman. Thus it would have been obvious to one of ordinary skill in the art to replace the WW-domain peptide of Ullman with the ITCH protein of UNI1, as one of ordinary skill in the art would have been able to carry out such a simple substitution with a reasonable expectation of success because both Ullman and UNI1 describe WW-containing peptides.
Therefore, the invention of claims 7-8 and 10 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claims 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Ullman as applied to claims 1-2, 24, 33-34, 37-38, 41-42 and 47 above, and further in view of UniProt Accession No. U5I868 (1 page, 07/31/2019; cited on the attached Form PTO-892; herein referred to as UNI2).
Claim 12 is drawn to the fusion protein of claim 1, wherein the transmembrane domain is a M2 transmembrane domain as elected.
Claim 13 is drawn to the fusion protein of claim 1, wherein the transmembrane domain comprises a sequence having at least 95% identity to the sequence of SEQ ID NO: 9 as elected.
The teachings of Ullman as applied to claims 1-2, 24, 33-34, 37-38, 41-42 and 47 are discussed above. Ullman does not teach a M2 transmembrane domain.
Regarding claims 12-13, UNI2 discloses a fragment of influenza A matrix protein 2 (M2) characterized as having a transmembrane helix. Additionally, the M2 of UNI2 shares 100% sequence identity with SEQ ID NO: 9 [see Appendix B].
In view of UNI2, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to modify the fusion protein of Ullman by replacing the transmembrane domain of antibody in the fusion with the M2 of UNI2, since the simple substitution of known element for another results in a predictable result. One of ordinary skill in the art would have recognized that the transmembrane domain of the antibody in the fusion of Ullman and the M2 of UNI2 are transmembrane domains, and as such both are capable of being incorporated into fusion proteins as described by Ullman. Thus it would have been obvious to one of ordinary skill in the art to replace the transmembrane domain of the antibody in the fusion Ullman with the M2 of UNI2, as one of ordinary skill in the art would have been able to carry out such a simple substitution with a reasonable expectation of success because both Ullman and UNI2 describe peptides with transmembrane domains.
Therefore, the invention of claims 12-13 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claims 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Ullman in view of UNI2 as applied to claims 1-2, 24, 12-13, 33-34, 37-38, 41-42 and 47 above, and further in view of Betakova et al. (Arch Virol, 2009, 154:147; cited on the attached Form PTO-892; herein referred to as Betakova).
Claim 18 is drawn to the fusion protein of claim 1, wherein the extracellular domain is an influenza antigen domain.
Claim 19 is drawn to the fusion protein of claim 18, wherein the influenza antigen domain comprises an M2 extracellular domain as elected.
The teachings of Ullman and UNI2 as applied to claims 1-2, 24, 12-13, 33-34, 37-38, 41-42 and 47 are discussed above. These references do not teach an influenza antigen domain.
Betakova relates to the stability and function of the influenza A virus M2 ion channel protein [title].
Regarding claims 18-19, Betakova teaches the M2 protein contains an N-terminal extracellular domain and a transmembrane that are highly expressed at the surface of host cells to play an important role in the viral life cycle facilitating uncoating of virions in endosomes [p 147, col 2, para 1], and discloses an M2 protein from the Influenza A/Chicken/Germany/34 strain in [Figure 1] containing both a transmembrane domain and an extracellular domain. Betakova further teaches that the extracellular domain of the M2 protein is important for the protein’s incorporation into virions, and that this domain induces antibody production with inhibitory activity against viral replication [p 148, col 1, para 3 to col 2, para 1], and therefore one of skill in the art would recognize the extracellular domain of the M2 protein to be an antigen domain.
In view of Betakova, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to modify the combined fusion protein of Ullman and UNI2 by replacing the M2 transmembrane domain with the full M2 protein of Betakova, since the simple substitution of known element for another results in a predictable result. One of ordinary skill in the art would have recognized that the M2 transmembrane domain of the combined fusion of Ullman and UNI2 and the full M2 protein of Betakova both contain M2 transmembrane domains, and as such both are capable of being incorporated into fusion proteins as described by Ullman. Thus it would have been obvious to one of ordinary skill in the art to replace the M2 transmembrane domain with the full M2 protein of Betakova, as one of ordinary skill in the art would have been able to carry out such a simple substitution with a reasonable expectation of success because both UNI2 and Betakova describe M2 peptides with transmembrane domains.
Therefore, the invention of claims 18-19 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over Ullman in view of UNI2 and Betakova as applied to claims 1-2, 12-13, 18-19, 24, 33-34, 37-38, 41-42 and 47 above, and further in view of UniProt Accession NO. H8YTC7 (1 page, 07/31/2019; cited on the attached Form PTO-892; herein referred to as UNI3).
Claim 22 is drawn to the fusion protein of claim 1, wherein the extracellular domain comprises a sequence having at least 95% identity to the sequence of SEQ ID NO: 8.
The teachings of Ullman, UNI2 and Betakova as applied to claims 1-2, 12-13, 18-19, 24, 33-34, 37-38, 41-42 and 47 are discussed above. These references do not teach the extracellular domain comprises a sequence having at least 95% identity to the sequence of SEQ ID NO: 8.
Regarding claim 22, UNI3 teaches 23-amino acid fragment of M2 from Influenza A that shares 100% identity with SEQ ID NO: 8 [see Appendix C]. While UNI3 does not teach the fragment is the extracellular domain of M2, Betakova teaches the M2 extracellular domain consists of the 24 N-terminal amino acids of the 97 amino acid M2 protein [p 147, col 2, para 1] as depicted by [Figure 1]. Therefore one of skill in the art in comparing the M2 fragment of UNI3 with a full M2 protein such as the one of Betakova would reasonably conclude the M2 fragment of UNI3 is the extracellular domain of the corresponding influenza A strain [see Appendix D].
In view of UNI3, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to modify the combined fusion protein of Ullman, UNI2 and Betakova by replacing the extracellular domain with the M2 extracellular domain of UNI3, since the simple substitution of known element for another results in a predictable result. One of ordinary skill in the art would have recognized that the extracellular domain of the combined fusion of Ullman, UNI2 and Betakova and the M2 protein of UNI3 both contain M2 extracellular domains, and as such both are capable of being incorporated into fusion proteins as described by Ullman. Thus it would have been obvious to one of ordinary skill in the art to replace the extracellular domain of the combined fusion protein of Ullman, UNI2 and Betakova with the M2 extracellular domain of UNI3, as one of ordinary skill in the art would have been able to carry out such a simple substitution with a reasonable expectation of success because Betakova and UNI3 describe M2 peptides comprising extracellular domains.
Therefore, the invention of claim 22 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claim 46 is rejected under 35 U.S.C. 103 as being unpatentable over Ullman.
Claim 46 is drawn to a kit comprising the fusion protein of claim 1.
The teachings of Ullman as applied to claims 1-2, 24, 33-34, 37-38, 41-42 and 47 are discussed above. Ullman does not explicitly teach in a single embodiment a kit comprising a fusion protein.
Regarding claim 46, Ullman teaches the limitations regarding the fusion protein of claim 1 as discussed in the rejection of claim 1 above.
In view of Ullman, it would have been prima facie obvious for one of ordinary skill in the art before the effect filing date to incorporate the fusion protein into a kit to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to incorporate the fusion protein into a kit with a reasonable expectation of success because it is routine in the art to optimize reagents for reproducibility of results in their application, and such optimization would include incorporating the fusion protein of Ullman into a kit.
Therefore, the invention of claim 46 would have been obvious to one of ordinary skill in the art before the effective filing date.
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.
A. Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/032134 (herein “reference application”). Although the claims at issue are not identical, they are not patentably distinct from each other because of the following:
Regarding instant claim 1, claim 1 of the reference application recites a fusion protein comprising a WW-containing domain, a transmembrane domain, and an extracellular domain, wherein the extracellular domain is a coronavirus antigen domain.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 2, 24, 33-34, 37-38, 41-42 and 46-47 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/032134 in view of Ullman and evidentiary reference Tiller.
The claim of the reference application is discussed above. The claim of the reference application does not recite wherein the fusion protein does not comprise AARDC1 and/or wherein the WW-containing domain comprises at least one, two, three or four WW domains.
Ullman relates to modified WW-domain peptides that bind desired targeted ligands [abstract].
Regarding instant claim 2, Ullman discloses a modified WW domain peptide produced by recombinant DNA technology and standard expression and purification procedure [para 0084] that can have an attached second molecules such as an antibody [para 0086], wherein the modified WW domain peptide may be grown in a fusion with another protein [para 0084], and wherein antibodies are understood to contain both extracellular and transmembrane domains as evidenced by Tiller in [Figure 2], and wherein the fusion protein does not comprise an arrestin domain containing protein 1 (AARDC1).
In view of Ullman, it would have been obvious for one of skill in the art before the effective filing date to modify the claim of the reference application by replacing the fusion protein of the reference application with the fusion of Ullman to arrive at the claimed invention, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that the fusion protein of the claim of the reference application and the fusion protein of Ullman are both WW-domain containing fusion proteins, and as such both are fusion proteins as described by the reference application. Thus it would have been obvious to one of ordinary skill in the art to replace the fusion protein of the claim of the reference application with the fusion protein of Ullman, as one of ordinary skill in the art would have been able to carry out such a simple substitution with a reasonable expectation of success because the reference application and Ullman describe fusion proteins with WW-containing domains.
Regarding instant claim 24, the term “signal peptide” is not defined in the instant specification. The specification does define a “signal” or a “signal tag” to “refer [to] a molecule (e.g., peptide, nucleic acid, other moiety) associated with a subject molecule to identify the subject molecule during use” [para 0058]. Ullman discloses to aid in purifying peptides of the invention, the invention may include a purification sequence such as a His-tag [para 0084], which is considered to be a peptide molecule used to identify the subject molecule.
Regarding instant claim 33, Ullman discloses the modified WW domain peptide can be produced by standard expression and purification procedure that includes nucleic acid molecules encoding the peptide, such as expression vectors comprising the nucleic acid [para 0084], and that the nucleic acid may be isolated [para 0081].
Regarding instant claim 34, Ullman discloses the DNA encoding the relevant peptide can be inserted into a suitable expression vector (e.g. pGem) where it is operably linked to appropriate expression sequences and transformed into a suitable host cell for protein expression [para 0084], which is considered to correspond to a nucleic acid operably linked to an inducible promoter.
Regarding instant claim 37, Ullman discloses the modified WW domain peptide as described in the rejection of instant claim 1 may be mixed with a population of liposomes such as a lipid vesicle [para 0101], which corresponds to an extracellular vesicle comprising a fusion peptide and a lipid bilayer.
Regarding instant claim 38, the liposome-encapsulated modified WW domain peptide as described in the rejection of instant claim 37 is considered to not comprise any of CD63, CD81, CD9 and PTGFRN.
Regarding instant claims 41-42, Ullman discloses the modified WW domain peptide described in the rejection of instant claim 1 can be encoded by nucleic acids as described in the rejection of instant claim 33, inserted into a suitable expression vector such as a pGEM vector, and transformed into a suitable host cell for protein expression, wherein suitable host cells include bacteria, fungal cells and cells of higher eukaryotic origin [para 0084], wherein pGEM vectors are understood to contain heterologous promoters that drive expression of an encoded protein. As the phrase “A WAEV-producing cell” does not impart any structural characteristics on the cell of instant claims 41-42, the cell of Ullman satisfies all of the structural limitations of instant claims 41-42.
Regarding instant claim 46, Ullman discloses the limitations regarding the fusion protein of instant claim 1 as discussed in the rejection above. It would have been obvious for one of ordinary skill in the art before the effect filing date to incorporate the fusion protein into a kit to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to incorporate the fusion protein into a kit with a reasonable expectation of success because it is routine in the art to optimize reagents for reproducibility of results in their application, and such optimization would include incorporating the fusion protein of Ullman into a kit.
Regarding instant claim 47, the phrase “the fusion protein is further bound to a SCAMP3 protein or a variant thereof” is considered an intended use of the claimed fusion protein (see MPEP 2111.02.II), and does not provide any structural limitations on the claimed fusion protein. As the fusion protein of Ullman is encompassed by the structural limitations of claim 47, it is considered to satisfy the limitations of claim 47. Considering an alternative interpretation that the recited phrase limits the fusion protein to have a structure capable of binding SCAMP3, as the fusion protein of Ullman is encompassed by the structural limitations of claim 47, it is considered to have the capability of binding SCAMP3, as the function of a protein is considered to be inherent to its structure (see MPEP 2112).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 7-8 and 10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/032134 in view of Ullman as applied to claims 1-2, 24, 33-34, 37-38, 41-42 and 46-47 above, and further in view of UNI1.
The claim of the reference application and disclosure of Ullman as applied to claims 1-2, 24, 33-34, 37-38, 41-42 and 47 are discussed above. The claim of the reference application does not recite a NEDD3 E3 ligase domain as the WW-containing domain.
Regarding instant claims 7-8 and 10, UNI1 discloses an ITCH protein that is an E3 ubiquitin-protein ligase [p 1], wherein ITCH contains multiple WW domains [p 14], and shares 100% sequence identity with SEQ ID NO: 1 [see Appendix A].
In view of UNI1, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined fusion protein of the reference application and Ullman by replacing the WW-domain peptide with the peptide of UNI1, since the simple substitution of known element for another results in a predictable result. One of ordinary skill in the art would have recognized that the WW-domain peptide of the combined fusion protein of the reference application and Ullman and the ITCH protein of UNI1 are both WW-domain containing peptides, and as such both are capable of being incorporated into fusion proteins as described by Ullman. Thus it would have been obvious to one of ordinary skill in the art to replace the WW-domain peptide of the combined fusion protein of the reference application and Ullman with the ITCH protein of UNI1, as one of ordinary skill in the art would have been able to carry out such a simple substitution with a reasonable expectation of success because Ullman and UNI1 describe WW-containing peptides.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 12-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/032134 in view of Ullman as applied to claims 1-2, 24, 33-34, 37-38, 41-42 and 46-47 above, and further in view of UNI2.
The claim of the reference application and disclosure of Ullman as applied to claims 1-2, 24, 33-34, 37-38, 41-42 and 46-47 are discussed above. The claim of the reference application does not recite a M2 transmembrane domain.
Regarding instant claims 12-13, UNI2 discloses a fragment of influenza A matrix protein 2 (M2) characterized as having a transmembrane helix. Additionally, the M2 of UNI2 shares 100% sequence identity with SEQ ID NO: 9 [see Appendix B].
In view of UNI2, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined fusion protein of the reference application and Ullman by replacing the transmembrane domain of the antibody in the fusion with the M2 of UNI2, since the simple substitution of known element for another results in a predictable result. One of ordinary skill in the art would have recognized that the transmembrane domain of the antibody in the combined fusion protein of the reference application and Ullman and the M2 of UNI2 are transmembrane domains, and as such both are capable of being incorporated into fusion proteins as described by Ullman. Thus it would have been obvious to one of ordinary skill in the art to replace the transmembrane domain of the antibody in the combined fusion protein of the reference application and Ullman with the M2 of UNI2, as one of ordinary skill in the art would have been able to carry out such a simple substitution with a reasonable expectation of success because both Ullman and UNI2 describe peptides with transmembrane domains.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 18-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/032134 in view of Ullman and UNI2 as applied to claims 1-2, 12-13, 24, 33-34, 37-38, 41-42 and 46-47 above, and further in view of Betakova.
The claims of the reference application and disclosures of Ullman and UNI2 as applied to claims 1-2, 12-13, 24, 33-34, 37-38, 41-42 and 46-47 are discussed above. The claims of the reference application do not recite an influenza antigen domain.
Betakova relates to the stability and function of the influenza A virus M2 ion channel protein [title].
Regarding instant claims 18-19, Betakova discloses the M2 protein contains an N-terminal extracellular domain and a transmembrane that are highly expressed at the surface of host cells to play an important role in the viral life cycle facilitating uncoating of virions in endosomes [p 147, col 2, para 1], and discloses an M2 protein from the Influenza A/Chicken/Germany/34 strain in [Figure 1] containing both a transmembrane domain and an extracellular domain. Betakova further discloses that the extracellular domain of the M2 protein is important for the protein’s incorporation into virions, and that this domain induces antibody production with inhibitory activity against viral replication [p 148, col 1, para 3 to col 2, para 1], and therefore one of skill in the art would recognize the extracellular domain of the M2 protein to be an antigen domain.
In view of Betakova, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined fusion protein of the reference application, Ullman and UNI2 by replacing the M2 transmembrane domain with the full M2 protein of Betakova, since the simple substitution of known element for another results in a predictable result. One of ordinary skill in the art would have recognized that the M2 transmembrane domain of the combined fusion protein of the reference application, Ullman and UNI2 and the full M2 protein of Betakova both contain M2 transmembrane domains, and as such both are capable of being incorporated into fusion proteins as described by Ullman. Thus it would have been obvious to one of ordinary skill in the art to replace the M2 transmembrane domain with the full M2 protein of Betakova, as one of ordinary skill in the art would have been able to carry out such a simple substitution with a reasonable expectation of success because both UNI2 and Betakova describe M2 peptides with transmembrane domains.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 22 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/032134 in view of Ullman, UNI2 and Betakova as applied to claims 1-2, 12-13, 18-19, 24, 33-34, 37-38, 41-42 and 46-47 above, and further in view of UNI3.
The claim of the reference application and disclosures of Ullman, UNI2 and Betakova as applied to claims 1-2, 12-13, 18-19, 24, 33-34, 37-38, 41-42 and 46-47 are discussed above. The claim of the reference application does not recite the extracellular domain comprises a sequence having at least 95% identity to the sequence of SEQ ID NO: 8.
Regarding instant claim 22, UNI3 discloses 23-amino acid fragment of M2 from Influenza A that shares 100% identity with SEQ ID NO: 8 [see Appendix C]. While UNI3 does not disclose the fragment is the extracellular domain of M2, Betakova teaches the M2 extracellular domain consists of the 24 N-terminal amino acids of the 97 amino acid M2 protein [p 147, col 2, para 1] as depicted by [Figure 1]. Therefore one of skill in the art in comparing the M2 fragment of UNI3 with a full M2 protein such as the one of Betakova would reasonably conclude the M2 fragment of UNI3 is the extracellular domain of the corresponding influenza A strain [see Appendix D].
In of UNI3, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined fusion protein of the reference application, Ullman, UNI2 and Betakova by replacing the extracellular domain with the M2 extracellular domain of UNI3, since the simple substitution of known element for another results in a predictable result. One of ordinary skill in the art would have recognized that the extracellular domain of the combined fusion protein of the reference application, Ullman, UNI2 and Betakova and the M2 protein of UNI3 both contain M2 extracellular domains, and as such both are capable of being incorporated into fusion proteins as described by Ullman. Thus it would have been obvious to one of ordinary skill in the art to replace the extracellular domain of the combined fusion protein of the reference application, Ullman, UNI2 and Betakova with the M2 extracellular domain of UNI3, as one of ordinary skill in the art would have been able to carry out such a simple substitution with a reasonable expectation of success because Betakova and UNI3 describe M2 peptides with extracellular domains.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
B. Claims 1-2, 7-8, 24, 33-34, 37-38, 41-42 and 46-47 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 7-8, 18, 27-28, 31-32, 35-36 and 40-41 of copending Application No. 18/032140 (herein “reference application”). Although the claims at issue are not identical, they are not patentably distinct from each other because of the following:
Regarding instant claim 1, claim 1 of the reference application recites a fusion protein comprising a WW-containing domain, a transmembrane domain, and an extracellular domain, wherein the extracellular domain is an HIV antigen domain.
Regarding instant claim 2, claim 2 of the reference application recites the fusion protein does not comprise an AARDC1.
Regarding instant claim 7, claim 7 of the reference application recites wherein the WW-containing domain is a NEDD4 E3 ligase domain.
Regarding instant claim 8, claim 8 of the reference application recites wherein the NEDD4 E3 Ligase is ITCH.
Regarding instant claim 24, claim 18 of the reference application recites the fusion comprises a signal peptide.
Regarding instant claim 33, claim 27 of the reference application recites an isolated nucleic acid encoding the fusion protein.
Regarding instant claim 34, claim 28 of the reference application recites the isolated nucleic acid is operably linked to a promoter that is a constitutive promoter.
Regarding instant claim 37, claim 31 of the reference application recites a WAEV comprising a lipid bilayer and the fusion protein.
Regarding instant claim 38, claim 32 of the reference application recites the WAEV comprises SCAMP3.
Regarding instant claim 41, claim 35 of the reference application recites a WAEV producing cell comprising a recombinant expression construct encoding the fusion protein under the control of a heterologous promoter
Regarding instant claim 42, claim 36 of the reference application recites a WAEV-producing cell comprising the isolated nucleic acid of claim 27.
Regarding instant claim 46, claim 40 of the reference application recites a kit comprising the fusion protein.
Regarding instant claim 47, claim 41 of the reference application recites the fusion protein is further bound to a SCAMP protein.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 10 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 7-8, 18, 27-28, 31-32, 35-36 and 40-41 of copending Application No. 18/032140 as applied to claims 1-2, 7-8, 24, 33-34, 37-38, 41-42 and 46-47 above, and further in view of UNI1.
The claims of the reference application as applied to claims 1-2, 7-8, 24, 33-34, 37-38, 41-42 and 46-47 are discussed above. The claims of the reference application do not recite the sequence limitations of instant claim 10.
Regarding instant claim 10, UNI1 discloses an ITCH protein that is an E3 ubiquitin-protein ligase [p 1], wherein ITCH contains multiple WW domains [p 14], and shares 100% sequence identity with SEQ ID NO: 1 [see Appendix A].
In view of UNI1, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by replacing the WW-domain peptide with the peptide of UNI1, since the simple substitution of known element for another results in a predictable result. One of ordinary skill in the art would have recognized that the WW-domain peptide of the reference application and the ITCH protein of UNI1 are both WW-domain containing peptides, and as such both are capable of being incorporated into fusion proteins as described by Ullman. Thus it would have been obvious to one of ordinary skill in the art to replace the WW-domain peptide of the reference application with the ITCH protein of UNI1, as one of ordinary skill in the art would have been able to carry out such a simple substitution with a reasonable expectation of success because the reference application and UNI1 describe WW-containing peptides.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 12-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 7-8, 18, 27-28, 31-32, 35-36 and 40-41 of copending Application No. 18/032140 as applied to claims 1-2, 7-8, 24, 33-34, 37-38, 41-42 and 46-47 above, and further in view of UNI2.
The claims of the reference application as applied to claims 1-2, 7-8, 24, 33-34, 37-38, 41-42 and 46-47 are discussed above. The claims of the reference application do not recite a M2 transmembrane domain.
Regarding instant claims 12-13, UNI2 discloses a fragment of influenza A matrix protein 2 (M2) characterized as having a transmembrane helix. Additionally, the M2 of UNI2 shares 100% sequence identity with SEQ ID NO: 9 [see Appendix B].
In view of UNI2, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the fusion protein of the reference application by replacing the transmembrane domain of the antibody in the fusion with the M2 of UNI2, since the simple substitution of known element for another results in a predictable result. One of ordinary skill in the art would have recognized that the transmembrane domain of the fusion protein of the reference application and the M2 of UNI2 are transmembrane domains, and as such both are capable of being incorporated into fusion proteins as described by Ullman. Thus it would have been obvious to one of ordinary skill in the art to replace the transmembrane domain of the fusion protein of the reference application with the M2 of UNI2, as one of ordinary skill in the art would have been able to carry out such a simple substitution with a reasonable expectation of success because both the reference application and UNI2 describe peptides with transmembrane domains.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 18-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 7-8, 18, 27-28, 31-32, 35-36 and 40-41 of copending Application No. 18/032140 in view UNI2 as applied to claims 1-2, 7-8, 12-13, 24, 33-34, 37-38, 41-42 and 46-47 above, and further in view of Betakova.
The claims of the reference application and disclosures of UNI2 as applied to claims 1-2, 7-8, 12-13, 24, 33-34, 37-38, 41-42 and 46-47 are discussed above. The claims of the reference application do not recite an influenza antigen domain.
Betakova relates to the stability and function of the influenza A virus M2 ion channel protein [title].
Regarding instant claims 18-19, Betakova discloses the M2 protein contains an N-terminal extracellular domain and a transmembrane that are highly expressed at the surface of host cells to play an important role in the viral life cycle facilitating uncoating of virions in endosomes [p 147, col 2, para 1], and discloses an M2 protein from the Influenza A/Chicken/Germany/34 strain in [Figure 1] containing both a transmembrane domain and an extracellular domain. Betakova further discloses that the extracellular domain of the M2 protein is important for the protein’s incorporation into virions, and that this domain induces antibody production with inhibitory activity against viral replication [p 148, col 1, para 3 to col 2, para 1], and therefore one of skill in the art would recognize the extracellular domain of the M2 protein to be an antigen domain.
In view of Betakova, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined fusion protein of the reference application and UNI2 by replacing the M2 transmembrane domain with the full M2 protein of Betakova, since the simple substitution of known element for another results in a predictable result. One of ordinary skill in the art would have recognized that the M2 transmembrane domain of the combined fusion protein of the reference application and UNI2 and the full M2 protein of Betakova both contain M2 transmembrane domains, and as such both are capable of being incorporated into fusion proteins as described by Ullman. Thus it would have been obvious to one of ordinary skill in the art to replace the M2 transmembrane domain with the full M2 protein of Betakova, as one of ordinary skill in the art would have been able to carry out such a simple substitution with a reasonable expectation of success because both UNI2 and Betakova describe M2 peptides with transmembrane domains.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 22 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 7-8, 18, 27-28, 31-32, 35-36 and 40-41 of copending Application No. 18/032140 in view of UNI2 and Betakova as applied to claims 1-2, 7-8, 12-13, 18-19, 24, 33-34, 37-38, 41-42 and 46-47 above, and further in view of UNI3.
The claims of the reference application and disclosures of UNI2 and Betakova as applied to claims 1-2, 7-8, 12-13, 18-19, 24, 33-34, 37-38, 41-42 and 46-47 are discussed above. The claims of the reference application do not recite the extracellular domain comprises a sequence having at least 95% identity to the sequence of SEQ ID NO: 8.
Regarding instant claim 22, UNI3 discloses 23-amino acid fragment of M2 from Influenza A that shares 100% identity with SEQ ID NO: 8 [see Appendix C]. While UNI3 does not disclose the fragment is the extracellular domain of M2, Betakova teaches the M2 extracellular domain consists of the 24 N-terminal amino acids of the 97 amino acid M2 protein [p 147, col 2, para 1] as depicted by [Figure 1]. Therefore one of skill in the art in comparing the M2 fragment of UNI3 with a full M2 protein such as the one of Betakova would reasonably conclude the M2 fragment of UNI3 is the extracellular domain of the corresponding influenza A strain [see Appendix D].
In of UNI3, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined fusion protein of the reference application, UNI2 and Betakova by replacing the extracellular domain with the M2 extracellular domain of UNI3, since the simple substitution of known element for another results in a predictable result. One of ordinary skill in the art would have recognized that the extracellular domain of the combined fusion protein of the reference application, UNI2 and Betakova and the M2 protein of UNI3 both contain M2 extracellular domains, and as such both are capable of being incorporated into fusion proteins as described by Ullman. Thus it would have been obvious to one of ordinary skill in the art to replace the extracellular domain of the combined fusion protein of the reference application, UNI2 and Betakova with the M2 extracellular domain of UNI3, as one of ordinary skill in the art would have been able to carry out such a simple substitution with a reasonable expectation of success because Betakova and UNI3 describe M2 peptides with extracellular domains.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
C. Claims 1-2, 24, 33-34, 37-38, 41-42 and 46-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11-12 of U.S. Patent No. 11,730,823 (cited on the IDS filed 12/27/2023; herein “patent”) in view of Ullman.
Regarding instant claim 1, claim 11 of the patent recites a fusion protein comprising an AARDC1-protein and an RNA binding protein, and
claim 12 of the patent recites the RNA binding protein comprises a WW domain.
The claims of the patent do not recite an extracellular domain or a transmembrane domain.
Ullman relates to modified WW-domain peptides that bind desired targeted ligands [abstract].
Regarding instant claims 1-2, Ullman discloses a modified WW domain peptide produced by recombinant DNA technology and standard expression and purification procedure [para 0084] that can have an attached second molecules such as an antibody [para 0086], wherein the modified WW domain peptide may be grown in a fusion with another protein [para 0084], and wherein antibodies are understood to contain both extracellular and transmembrane domains as evidenced by Tiller in [Figure 2], and wherein the fusion protein does not comprise an arrestin domain containing protein 1 (AARDC1).
In view of Ullman, it would have been obvious for one of skill in the art before the effective filing date to modify the claims of the patent by replacing the fusion protein of the patent with the fusion of Ullman to arrive at the claimed invention, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that the fusion protein of the patent and the fusion protein of Ullman are both WW-domain containing fusion proteins, and as such both are fusion proteins as described by the patent. Thus it would have been obvious to one of ordinary skill in the art to replace the fusion protein of the patent with the fusion protein of Ullman, as one of ordinary skill in the art would have been able to carry out such a simple substitution with a reasonable expectation of success because the patent and Ullman describe fusion proteins with WW-containing domains.
Regarding instant claim 24, the term “signal peptide” is not defined in the instant specification. The specification does define a “signal” or a “signal tag” to “refer [to] a molecule (e.g., peptide, nucleic acid, other moiety) associated with a subject molecule to identify the subject molecule during use” [para 0058]. Ullman discloses to aid in purifying peptides of the invention, the invention may include a purification sequence such as a His-tag [para 0084], which is considered to be a peptide molecule used to identify the subject molecule.
Regarding instant claim 33, Ullman discloses the modified WW domain peptide can be produced by standard expression and purification procedure that includes nucleic acid molecules encoding the peptide, such as expression vectors comprising the nucleic acid [para 0084], and that the nucleic acid may be isolated [para 0081].
Regarding instant claim 34, Ullman discloses the DNA encoding the relevant peptide can be inserted into a suitable expression vector (e.g. pGem) where it is operably linked to appropriate expression sequences and transformed into a suitable host cell for protein expression [para 0084], which is considered to correspond to a nucleic acid operably linked to an inducible promoter.
Regarding instant claim 37, Ullman discloses the modified WW domain peptide as described in the rejection of instant claim 1 may be mixed with a population of liposomes such as a lipid vesicle [para 0101], which corresponds to an extracellular vesicle comprising a fusion peptide and a lipid bilayer.
Regarding instant claim 38, the liposome-encapsulated modified WW domain peptide as described in the rejection of instant claim 37 is considered to not comprise any of CD63, CD81, CD9 and PTGFRN.
Regarding instant claims 41-42, Ullman discloses the modified WW domain peptide described in the rejection of instant claim 1 can be encoded by nucleic acids as described in the rejection of instant claim 33, inserted into a suitable expression vector such as a pGEM vector, and transformed into a suitable host cell for protein expression, wherein suitable host cells include bacteria, fungal cells and cells of higher eukaryotic origin [para 0084], wherein pGEM vectors are understood to contain heterologous promoters that drive expression of an encoded protein. As the phrase “A WAEV-producing cell” does not impart any structural characteristics on the cell of instant claims 41-42, the cell of Ullman satisfies all of the structural limitations of instant claims 41-42.
Regarding instant claim 46, Ullman discloses the limitations regarding the fusion protein of instant claim 1 as discussed in the rejection above. It would have been obvious for one of ordinary skill in the art before the effect filing date to incorporate the fusion protein into a kit to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to incorporate the fusion protein into a kit with a reasonable expectation of success because it is routine in the art to optimize reagents for reproducibility of results in their application, and such optimization would include incorporating the fusion protein of Ullman into a kit.
Regarding instant claim 47, the phrase “the fusion protein is further bound to a SCAMP3 protein or a variant thereof” is considered an intended use of the claimed fusion protein (see MPEP 2111.02.II), and does not provide any structural limitations on the claimed fusion protein. As the fusion protein of Ullman is encompassed by the structural limitations of claim 47, it is considered to satisfy the limitations of claim 47. Considering an alternative interpretation that the recited phrase limits the fusion protein to have a structure capable of binding SCAMP3, as the fusion protein of Ullman is encompassed by the structural limitations of claim 47, it is considered to have the capability of binding SCAMP3, as the function of a protein is considered to be inherent to its structure (see MPEP 2112).
Claims 7-8 and 10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11-12 of U.S. Patent No. 11,730,823 in view of Ullman as applied to claims 1-2, 24, 33-34, 37-38, 41-42 and 46-47 above, and further in view of UNI1.
The claims of the patent and disclosure of Ullman as applied to claims 1-2, 24, 33-34, 37-38, 41-42 and 46-47 are discussed above. The claims of the patent do not recite a NEDD3 E3 ligase domain as the WW-containing domain.
Regarding instant claims 7-8 and 10, UNI1 discloses an ITCH protein that is an E3 ubiquitin-protein ligase [p 1], wherein ITCH contains multiple WW domains [p 14], and shares 100% sequence identity with SEQ ID NO: 1 [see Appendix A].
In view of UNI1, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined fusion protein of the patent and Ullman by replacing the WW-domain peptide with the peptide of UNI1, since the simple substitution of known element for another results in a predictable result. One of ordinary skill in the art would have recognized that the WW-domain peptide of the combined fusion protein of the patent and Ullman and the ITCH protein of UNI1 are both WW-domain containing peptides, and as such both are capable of being incorporated into fusion proteins as described by Ullman. Thus it would have been obvious to one of ordinary skill in the art to replace the WW-domain peptide of the combined fusion protein of the patent and Ullman with the ITCH protein of UNI1, as one of ordinary skill in the art would have been able to carry out such a simple substitution with a reasonable expectation of success because Ullman and UNI1 describe WW-containing peptides.
Claims 12-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11-12 of U.S. Patent No. 11,730,823 in view of Ullman as applied to claims 1-2, 24, 33-34, 37-38, 41-42 and 46-47 above, and further in view of UNI2.
The claims of the patent and disclosure of Ullman as applied to claims 1-2, 24, 33-34, 37-38, 41-42 and 46-47 are discussed above. The claims of the patent do not recite a M2 transmembrane domain.
Regarding instant claims 12-13, UNI2 discloses a fragment of influenza A matrix protein 2 (M2) characterized as having a transmembrane helix. Additionally, the M2 of UNI2 shares 100% sequence identity with SEQ ID NO: 9 [see Appendix B].
In view of UNI2, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined fusion protein of the patent and Ullman by replacing the transmembrane domain of the antibody in the fusion with the M2 of UNI2, since the simple substitution of known element for another results in a predictable result. One of ordinary skill in the art would have recognized that the transmembrane domain of the antibody in the combined fusion protein of the patent and Ullman and the M2 of UNI2 are transmembrane domains, and as such both are capable of being incorporated into fusion proteins as described by Ullman. Thus it would have been obvious to one of ordinary skill in the art to replace the transmembrane domain of the antibody in the combined fusion protein of the patent and Ullman with the M2 of UNI2, as one of ordinary skill in the art would have been able to carry out such a simple substitution with a reasonable expectation of success because both Ullman and UNI2 describe peptides with transmembrane domains.
Claims 18-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11-12 of U.S. Patent No. 11,730,823 in view of Ullman and UNI2 as applied to claims 1-2, 12-13, 24, 33-34, 37-38, 41-42 and 46-47 above, and further in view of Betakova.
The claims of the patent and disclosures of Ullman and UNI2 as applied to claims 1-2, 12-13, 24, 33-34, 37-38, 41-42 and 46-47 are discussed above. The claims of the patent do not recite an influenza antigen domain.
Betakova relates to the stability and function of the influenza A virus M2 ion channel protein [title].
Regarding instant claims 18-19, Betakova discloses the M2 protein contains an N-terminal extracellular domain and a transmembrane that are highly expressed at the surface of host cells to play an important role in the viral life cycle facilitating uncoating of virions in endosomes [p 147, col 2, para 1], and discloses an M2 protein from the Influenza A/Chicken/Germany/34 strain in [Figure 1] containing both a transmembrane domain and an extracellular domain. Betakova further discloses that the extracellular domain of the M2 protein is important for the protein’s incorporation into virions, and that this domain induces antibody production with inhibitory activity against viral replication [p 148, col 1, para 3 to col 2, para 1], and therefore one of skill in the art would recognize the extracellular domain of the M2 protein to be an antigen domain.
In view of Betakova, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined fusion protein of the patent, Ullman and UNI2 by replacing the M2 transmembrane domain with the full M2 protein of Betakova, since the simple substitution of known element for another results in a predictable result. One of ordinary skill in the art would have recognized that the M2 transmembrane domain of the combined fusion protein of the patent, Ullman and UNI2 and the full M2 protein of Betakova both contain M2 transmembrane domains, and as such both are capable of being incorporated into fusion proteins as described by Ullman. Thus it would have been obvious to one of ordinary skill in the art to replace the M2 transmembrane domain with the full M2 protein of Betakova, as one of ordinary skill in the art would have been able to carry out such a simple substitution with a reasonable expectation of success because both UNI2 and Betakova describe M2 peptides with transmembrane domains.
Claim 22 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11-12 of U.S. Patent No. 11,730,823 in view of Ullman, UNI2 and Betakova as applied to claims 1-2, 12-13, 18-19, 24, 33-34, 37-38, 41-42 and 46-47 above, and further in view of UNI3.
The claims of the patent and disclosures of Ullman, UNI2 and Betakova as applied to claims 1-2, 12-13, 18-19, 24, 33-34, 37-38, 41-42 and 46-47 are discussed above. The claims of the patent do not recite the extracellular domain comprises a sequence having at least 95% identity to the sequence of SEQ ID NO: 8.
Regarding instant claim 22, UNI3 discloses 23-amino acid fragment of M2 from Influenza A that shares 100% identity with SEQ ID NO: 8 [see Appendix C]. While UNI3 does not disclose the fragment is the extracellular domain of M2, Betakova teaches the M2 extracellular domain consists of the 24 N-terminal amino acids of the 97 amino acid M2 protein [p 147, col 2, para 1] as depicted by [Figure 1]. Therefore one of skill in the art in comparing the M2 fragment of UNI3 with a full M2 protein such as the one of Betakova would reasonably conclude the M2 fragment of UNI3 is the extracellular domain of the corresponding influenza A strain [see Appendix D].
In of UNI3, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined fusion protein of the patent, Ullman, UNI2 and Betakova by replacing the extracellular domain with the M2 extracellular domain of UNI3, since the simple substitution of known element for another results in a predictable result. One of ordinary skill in the art would have recognized that the extracellular domain of the combined fusion protein of the patent, Ullman, UNI2 and Betakova and the M2 protein of UNI3 both contain M2 extracellular domains, and as such both are capable of being incorporated into fusion proteins as described by Ullman. Thus it would have been obvious to one of ordinary skill in the art to replace the extracellular domain of the combined fusion protein of the patent, Ullman, UNI2 and Betakova with the M2 extracellular domain of UNI3, as one of ordinary skill in the art would have been able to carry out such a simple substitution with a reasonable expectation of success because Betakova and UNI3 describe M2 peptides with extracellular domains.
Allowable Subject Matter
The subject matter recited in claim 25 of “the fusion protein of claim 1, wherein the fusion protein comprises a sequence having at least 95% identity to the sequence of SEQ ID NO: 61 or SEQ ID NO: 62; or wherein the fusion protein comprises the sequence of SEQ ID NO: 61 or SEQ ID NO: 62; or wherein the fusion consists of the sequence of SEQ ID NO: 61 or SEQ ID NO: 62.” is free of the prior art of record.
Conclusion
Status of the Application:
Claims 1-2, 7-8, 10, 12-13, 18-19, 22, 24-25, 33-34, 37-38, 41-43 and 46-47 are pending.
Claim 43 is withdrawn.
Claims 1-2, 7-8, 10, 12-13, 18-19, 22, 24, 33-34, 37-38, 41-42 and 46-47 are rejected.
Claim 25 is objected to for a minor informality.
No claim is in condition for allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH SPANGLER whose telephone number is (571)270-0314. The examiner can normally be reached M-F 7:30 am - 4:30 pm.
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/JOSEPH R SPANGLER/
Examiner
Art Unit 1656
/David Steadman/Primary Examiner, Art Unit 1656
APPENDIX A
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330
629
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Alignment of SEQ ID NO: 1 with UniProt Accession No. Q96J02 (reference UNI1).
APPENDIX B
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154
635
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Alignment of SEQ ID NO: 9 with UniProt Accession No. U5I868 (reference UNI2).
APPENDIX C
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141
730
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Alignment of SEQ ID NO: 9 with UniProt Accession No. H8YTC7 (reference UNI3).
APPENDIX D
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141
730
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Alignment of M2 protein of Betakova with UniProt Accession No. H8YTC7 (reference UNI3).