DETALED 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 .
Status of the Application
1. Claims 1-2, 5-6, 10, 12, 14, 17, 24-26, 28, 32-33, 37-39 are pending and subject to examination on the merits. Claims 1-2, 10, 12, 14, 24-26, 32-33, 37, and 39 are withdrawn from consideration as being drawn to non-elected subject matter. New claim 39 is not commensurate in scope with the elected invention (group II) or the additional groups (groups I, III, and IV) and would be classified as its own group (group V), and is hereby, withdrawn. Claims 5-6, 17, 28, and 38 are currently under examination.
Election/Restrictions
2. Claims 1-2, 10, 12, 14, 24-26, 32-33, 37, and 39 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 18 June 2025.
Priority
3. Acknowledgement is made of applicant’s claim for foreign priority based on an application filed in KR KR10-2019-0117177 on 24 September 2019. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
4. The information disclosure statements (IDS) submitted on 23 March 2022, 17 October 2023, 02 February 2024, and 23 September 2024 have been considered by the examiner. See initialed and signed PTO/SB/08’s.
Drawings
5. The drawings are objected to because Fig. 12 is missing units on the x-axis. 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.
Specification
6. The use of the term Tamiflu™ and Relenza™ (p. 1), 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.
Compliance with Sequence Rules
7. The sequence listing, filed in computer readable form (CRF) and paper copy on , has been received and entered. This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 C.F.R. § 1.821(a)(1) and (a)(2). However, this application fails to fully comply with the requirements of 37 C.F.R. § 1.821 through 1.825; Applicants’ attention is directed to the final rulemaking notice published at 55 FR 18230 (May 1, 1990), and 1114 OG 29 (May 15, 1990).
The following parts of the Specification contain sequences that contain four or more specifically defined amino acids without any corresponding SEQ ID NO:
a) On pages 86, 95, 101, 106, GGGSGGGSGGGS needs a corresponding SEQ ID NO.
b) On pages 105-106, GGGS needs a corresponding SEQ ID NO.
Applicants must amend the specification to identify the sequences appropriately by SEQ ID NO:. — See also MPEP 2422.
Claim Objections
8. Claim 6 is objected to because of the following informalities: “an N-terminus” should be amended to “the N-terminus,” “a C-terminus” should be amended to “the C-terminus,” to improve grammar and clearly designate that there is only one C-terminus and one N-terminus of the fusion protein. Appropriate correction is required.
9. Claim 6 is objected to because of the following informalities: “an outer circumferential surface” should be amended to “the outer circumferential surface” to improve grammar and clearly designate that there is only one outer circumferential surface. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
10. The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
11. Claim 6 is indefinite. The claim recites “the plasmid according to claim 5” and proceeds to describe an N-terminal domain of an intein fused to the C-terminus of the fusion protein and a C-terminal domain of the intein fused to the N-terminus of the fusion protein. However, plasmids are not made up of proteins. To clarify the claim, it should be amended to recite “The plasmid according to claim 5, wherein the plasmid encodes an N-terminal…”
12. Claim 17 is indefinite. It is unclear where the plasmid is expressed, i.e. the plasmid being expressed in E. coli and subsequently purified. To mitigate this issue, the location of expression should be inserted into the claim.
Claim Rejections - 35 USC § 112(a)
13. 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.
Written Description:
14. Claims 5-6, 17, 28, and 38 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are drawn to a plasmid comprising an unknown nucleotide sequence encoding a fusion protein of an Fc region-binding peptide (Fcbp) and an unknown membrane protein (claims 5), wherein the fusion protein is used with an N-terminal domain of an intein at the C-terminus of the fusion protein and a C-terminal domain of the intein at the N-terminus of the fusion protein and the protein thereof (claim 6), further wherein the fusion protein surrounds an outer circumferential surface of a lipid bilayer nanodisc, making a nanoperforator (claim 28), and further wherein the nanoperforator is a pharmaceutical composition for preventing or treating an unknown viral infection comprising administering to a subject in need said pharmaceutical composition (claim 38).
MPEP 2163(1):
35 U.S.C. 112(a) and the first paragraph of pre-AIA 35 U.S.C. 112 require that the "specification shall contain a written description of the invention ...." This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en bane); Vas-Gath, Inc. v. Mahurkar, 935 F.2d 1555, 1560, 19 USPQ2d 1111, 1114 (Fed. Cir. 1991); see also Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920-23, 69 USPQ2d 1886, 1890-93 (Fed. Cir. 2004) (discussing the history and purpose of the written description requirement); In re Curtis, 354 F.3d 1347, 1357, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004) ("conclusive evidence of a claim's enablement is not equally conclusive of that claim's satisfactory written description"). The written description requirement has several policy objectives. "[T]he 'essential goal' of the description of the invention requirement is to clearly convey the information that an applicant [inventor] has invented the subject matter which is claimed." In re Barker, 559 F.2d 588, 592 n.4, 194 USPQ 470, 473 n.4 (CCPA 1977). Another objective is to convey to the public what the applicant claims as the invention. See Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1566, 43 USPQ2d 1398, 1404 (Fed. Cir. 1997), cert. denied, 523 U.S. 1089 (1998). "The 'written description' requirement implements the principle that a patent must describe the technology that is sought to be patented; the requirement serves both to satisfy the inventor's obligation to disclose the technologic knowledge upon which the patent is based, and to demonstrate that the patentee [inventor] was in possession of the invention that is claimed." Capon v. Eshhar, 418 F.3d 1349, 1357, 76 USPQ2d 1078, 1084 (Fed. Cir. 2005). Further, the written description requirement promotes the progress of the useful arts by ensuring that patentees adequately describe their inventions in their patent specifications in exchange for the right to exclude others from practicing the invention for the duration of the patent's term.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Gath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. However, a showing of possession alone does not cure the lack of a written description. Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 969-70, 63 USPQ2d 1609, 1617 (Fed. Cir. 2002). For example, it is now well accepted that a satisfactory description may be found in originally-filed claims or any other portion of the originally-filed specification. See In re Koller, 613 F.2d 819, 204 USPQ 702 (CCPA 1980); In re Gardner, 475 F.2d 1389, 177 USPQ 396 (CCPA 1973); In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). However, that does not mean that all originally-filed claims have adequate written support. The specification must still be examined to assess whether an originally-filed claim has adequate support in the written disclosure and/or the drawings.
15. The claims are drawn to a plasmid comprising an unknown nucleotide sequence encoding a fusion protein of an Fc region-binding peptide (Fcbp) and an unknown membrane protein (claims 5), wherein the fusion protein is used with an N-terminal domain of an intein at the C-terminus of the fusion protein and a C-terminal domain of the intein at the N-terminus of the fusion protein and the protein thereof (claim 6), further wherein the fusion protein surrounds an outer circumferential surface of a lipid bilayer nanodisc, making a nanoperforator (claim 28), and further wherein the nanoperforator is a pharmaceutical composition for preventing or treating an unknown viral infection comprising administering to a subject in need said pharmaceutical composition (claim 38). The variability in viruses and variability in the number of membrane scaffolding proteins in the FcBP-MSP split intein protein on a nano-perforator to treat said diseases coupled with the unpredictability or treating, let alone preventing, any of the viruses is enormous. At most the specification describes the production of a nanoperforator (esNP) containing end-spliced membrane scaffold protein, MSP1E3D1, flanked by CfaC-linker and CfaN-His tag as two different formulations. The nanoperforators were then introduced to influenza infected MDCK cells. Additionally, the specification describes a mouse study, where Balb/c mice were infected with PR8 virus and treated with the nanoperforator. The specification does not describe treating, let alone preventing, any other viruses. However, how the nanoperforator acts when incubated with a laboratory in vitro cell assay and a small mouse study, says absolutely nothing about treating, let alone preventing, any or all influenza viruses, let alone any virus. How a drug or biomaterial behaves in vitro or in a small mouse study with a specific viral strain is not necessarily predictive of how it will behave in vivo to circulating influenza viruses, or any other virus. Here the specification is incomplete and it mandates that those skilled in the art must then figure out how to use the aimed invention. Thus, the claims do not find adequate support in any place in the specification to show that possession of a compound with any membrane scaffolding protein on a nanoperforator for treating or preventing any viruses with said nanoperforator composition.
The courts have established:
Novozymes A/S v. DuPont Nutrition Biosciences APS, 723 F.3d 1336 (Fed. Cir. 2013):
A patent, however, "is not a reward for the search, but compensation for its successful conclusion." Ariad, 598 F.3d at 1353 (quoting University of Rochester, 358 F.3d at 930 n.10). For that reason, the written description requirement prohibits a patentee from "leaving it to the ... industry to complete an ufinished invention.” Id.
Enablement:
16. Claims 5-6, 17, 28, and 38 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a nanoperforator (esNP) containing end-spliced membrane scaffold protein, MSP1E3D1, flanked by CfaC-linker and CfaN-His tag as two different formulations does not reasonably provide enablement for all of the general membrane scaffolding proteins and any and all viruses and viral infections. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims without significant undue experimentation.
The factors to be considered in determining whether undue experimentation is required are summarized In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). The court in Wands states:
"Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is 'undue,' not 'experimentation.' " (Wands, 8 USPQ2d 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations." (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.
The claims in their broadest are drawn to a plasmid comprising an unknown nucleotide sequence encoding a fusion protein of an Fc region-binding peptide (Fcbp) and an unknown membrane protein (claims 5), wherein the fusion protein is used with an N-terminal domain of an intein at the C-terminus of the fusion protein and a C-terminal domain of the intein at the N-terminus of the fusion protein and the protein thereof (claim 6), further wherein the fusion protein surrounds an outer circumferential surface of a lipid bilayer nanodisc, making a nanoperforator (claim 28), and further wherein the nanoperforator is a pharmaceutical composition for preventing or treating an unknown viral infection comprising administering to a subject in need said pharmaceutical composition (claim 38). The direction and guidance coupled with the working examples of the application, however, are drawn only to demonstrating two specific working example of the composition, utilizing one very specific membrane scaffolding protein and one very specific virus in cell culture and one very specific virus in a small mouse study; specifically the production of a nanoperforator (esNP) containing end-spliced membrane scaffold protein, MSP1E3D1, flanked by CfaC-linker and CfaN-His tag as two different formulations. The nanoperforators were then introduced to influenza infected MDCK cells. Additionally, the specification describes a mouse study, where Balb/c mice were infected with PR8 virus and treated with the nanoperforator.
The quantity experimentation would be considerable because, while the relative skill level in the art is high (PhD or MD), they would be required to ascertain which membrane proteins, composition of the nanoperforator, i.e. what lipids, and what virus can be used and/or produced. It would be extremely difficult to be able to discern which viruses and/or membrane scaffolding proteins in a nanoperforator formulation would be successful.
It would be almost impossible to reliably predict the combination and/or combinations necessary to produce the claimed plasmid/composition and subsequently use said composition in a pharmaceutical composition to treat and/or prevent any viral infection.
Claim Rejections - 35 USC § 102
17. 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.
18. 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.
19. Claims 5 and 17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Umlauf et al (Umlauf et al., 2019, Sci. Adv.—cited herein). Regarding claims 5 and 17, drawn to a plasmid comprising a nucleotide sequence encoding a fusion protein of an Fc region-binding peptide (Fcbp) and a membrane scaffold protein (claim 5) and wherein, an antibody-binding membrane scaffold protein (FcBP-MSP) is produced by expressing said plasmid and purifying it (claim 17), Umlauf et al. teaches lamprey antigen receptors, known as variable lymphocyte receptors (VLRs), which are membrane proteins, that recognize antigenic targets with specificity and affinity comparable to Ig based antibodies (p. 1, column 2, 2nd paragraph). Specifically, Umlauf et al. teaches Intein expression protein ligation by cloning VLRs into pCTre vector fused to an engineered 202-08 intein (p. 10, Intein EPL), where expressed VLRs are doped into liposome formulations to determine immobilization and subsequent binding to murine brain sections (p. 6, column 2, 1st paragraph). Additionally, Umlauf et al. teaches a VLR Fc fusion protein, where VLRs were cloned into a pIRES vector and fused to a rabbit Fc region to facilitate avidity and detection while minimizing renal clearance (p. 5, 1st paragraph; p. 10, VLR rabbit Fc fusions).
Claim Rejections - 35 USC § 103
20. 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.
21. Claim 6 are rejected under 35 U.S.C. 103 as being unpatentable over Umlauf et al (Umlauf et al., 2019, Sci. Adv.—cited herein) as applied to claims 5 and 17 above, and in further view of Shah and Muir (Shah and Muir, 2011, Isr J Chem—cited herein).
The teachings of Umlauf et al. are discussed above and incorporated into the instant rejection.
Umlauf et al. does not teach a split intein expression vector, wherein an N-terminal domain of an intein is fused to the C-terminus of the fusion protein and a C-terminal domain of the intein is fused to the N-terminus of the fusion protein. Regarding the split intein system, Shah and Muir teach the utilization of SspDnaE intein in the cyclization of proteins and peptides, where the order of the intein fragments around the polypeptide of interest are inverted (IntC-target-IntN), where the target sequence can be head to tail cyclized. Further, Shah and Muir teach that this production method of circular proteins provides enhanced biological properties conferred by their augmented stability (p. 3, 1st paragraph; Fig. 2b).
Therefore, it 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 combine the teachings of Umlauf et al. and Shah and Muir to create a plasmid with a split intien fusion protein of a membrane protein and an Fc binding peptide because split intein systems cab confer enhanced stability for recombinant proteins, as taught by Shah and Muir above. One would be motivated to combine these teachings to arrive at the instant claims to modulate protein-protein interactions and molecules that reduce the cellular pathology of Parkinson’s disease as taught by Shah and Muir (p. 3, 1st paragraph). Therefore, it 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 to combine the teachings of Umlauf et al. and Shah and Muir to create a plasmid with a split intein fusion protein of a membrane protein and an Fc binding peptide, since Umlauf et al. teaches the utilization of an intein system with the fusion protein and Shah and Muir et al. teaches the advantages of the split intein system over the single intein containing plasmid.
22. Claims 28 and 38 are rejected under 35 U.S.C. 103 as being unpatentable over Umlauf et al (Umlauf et al., 2019, Sci. Adv.—cited herein) as applied to claims 5 and 17 above, and in further view of Kong et al (Kong et al., 2019, Nature Communications—cited on the Information Disclosure Statement dated 23 March 2022).
The teachings of Umlauf et al. are discussed above and incorporated into the instant rejection.
Umaluaf et al. does not teach the utilization of a nanodisc containing fusion protein or a subsequent pharmaceutical composition thereof. Kong et al. teach nanodiscs carrying a viral receptor sialic acid to bind to influenza virions and co-endocytize the bound virion and nanodisc into cells, where the virus is then broken down in the endolysosome by enzymatic decomposition (abstract). Specifically, Kong et al. teaches NDopt (optimized nanodiscs with viral receptor sialic acid), where the in vivo efficacy of NDopt was examined by intranasal inoculation of BALB/c mice with H1N1 (p. 4, last paragraph- p. 5, first paragraph ; Fig. 3). Kong et al. teaches that the structure of a planar lipid bilayer provided another dimension for antiviral activity of decoy molecules by perforating viral envelope (p. 5, Discussion). Additionally, Kong et al. teaches that the nanodiscs are self-assembled discoidal phospholipid bilayers wrapped by two copies of amphipathic membrane scaffold protein, an engineered form of apolipoprotein A1 and a constituent of high density lipoproteins (p. 2; Result, first paragraph).
Therefore, it 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 combine the teachings of Umlauf et al. in further view of Kong et al. to create Fc conjugated membrane proteins on a nanodisc because nanodiscs as therapeutics are promising as taught by Kong et al (p. 6; 2nd column, paragraph 2). One would be motivated to combine these teachings to arrive at the instant claims to develop nanodiscs containing fusion proteins, since there was no apparent toxicity and there are many possible approaches to improve in vivo efficacy, as taught by Kong et al (p. 6, column 2, paragraph 2). There would be reasonable expectation of success, yielding no surprising results when combining the teachings of Umlauf et al. in further view of Kong et al. to make a pharmaceutical compound with a nano-perforator conjugated with a fusion protein comprising an Fc binding domain peptide with a membrane scaffold, since Kong et al. teaches the utilization of a nano-perforator containing membrane protein.
Conclusion
23. All claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CIARA A MCKNIGHT whose telephone number is (703)756-4791. The examiner can normally be reached M-F 8:00am-4:30pm.
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/CIARA A MCKNIGHT/Examiner, Art Unit 1656
/SUZANNE M NOAKES/ Primary Examiner, Art Unit 1656