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 .
DETAILED ACTION
Acknowledgement is hereby made of receipt and entry of the communication filed on July 09, 2026, and Jan. 09, 2024. Claims 1-20 are pending. Claims 11-20 are withdrawn. Claims 1-10 are currently examined.
Election/Restrictions
Applicant's election without traverse of Group I (claims 1-10), in the reply filed on July 09, 2026, is acknowledged.
Accordingly, claims 11-20 are withdrawn as being directed to a non-elected group.
Claim Rejections - 35 USC § 112 (b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION. —The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The base claim 1 recites a term “specific interaction event” that renders the claims indefinite. It is unclear what the “specific interaction event” is among the cell receptor, nanoparticle and the enveloped virus.
Therefore, one of ordinary skill in the art cannot determine the exact metes and bounds of the claim.
Claim Rejections - 35 USC § 112 (Enablement)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-4 and 7-10 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to 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 base claim 1 contains subject matter which was not described in the specification in such a way as to 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. Enablement is considered in view of the Wands factors (MPEP 2164.01(a)) (1) the nature of the invention, (2) the state of the prior art, 3) the breadth of the claims, (4) the amount of guidance in the specification, (5) the presence or absence of working examples, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and 8) and the quantity of experimentation necessary.
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
The base claim 1 is directed to a method of neutralizing an enveloped virus comprising: a) providing a nanoparticle comprising a surface exposed cell receptor molecule that mediates entry of an enveloped virus into host cells; and b) administering the nanoparticle to an individual having or at risk of infection with the enveloped virus, wherein the cell receptor mediates a specific interaction event between the nanoparticle and the enveloped virus.
The instant specification discloses a method for liposome preparation and characterization and a method for constructing the pseudoviruses bearing the spike protein of SARS-CoV-2 in Example 1(See [0078]; (See [0080]; [0081])).
In Example 2, the instant specification discloses a method for how to synthesize, characterize and modify ACE2 onto the liposome surface (See [0083]). The neutralizing test is measured by the reduction in luciferase gene expression using SARS-CoV-2 pseudovirus in 293T cell (See [0081], [0085] and [0086]). Example 3 in the specification is the discussions regarding the rhACE2 liposomes and Covid-19 and the pseudotyped SARS-COV-2 that including the liposomes potently inhibiting viral entry of pseudotyped SARS-CoV-2 into host cells by extracting the spike proteins from the pseudovirus surface (See [0087] to [0090]).
Based on the description above, the instant specification only provides evidence to support a nanoparticle comprising ACE2 receptor with capability to neutralize the psedutyped SARS-COV-2 in 293T cells. However, the instant base claim 1 is directed to a method of neutralizing any enveloped virus by any nanoparticle with a generic cell receptor in any host cells. Here the instant specification does not provide a method to support for neutralizing any enveloped virus in any cells by any nanoparticle with conjugation of any cell receptor.
Furthermore, the base claim 1 also requires administering a generic nanoparticle to an individual having or at risk of infection with any enveloped virus. However, the instant specification does not disclose any in vivo experiment including the administration of the claimed nanoparticles.
Accordingly, when all the aforementioned factors are considered in total, it would require undue experimentation for one skilled in the art to practice the full scope of claimed invention as defined by instant claims. Therefore, claims 1-4 and 7-10 are rejected under 35 USC § 112 (Enablement).
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 1-3, 5 and 7-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chen et al. (Matter. 2021 Jun 2;4(6):2059-2082. Epub 2021 Apr 22, hereinafter, “Chen”).
The base claim 1 is directed to a method of neutralizing an enveloped virus comprising:
a) providing a nanoparticle comprising a surface exposed cell receptor molecule that mediates entry of an enveloped virus into host cells; and
b) administering the nanoparticle to an individual having or at risk of infection with
the enveloped virus, wherein the cell receptor mediates a specific interaction event between the nanoparticle and the enveloped virus.
Chen describes the nanotraps for the containment and clearance of SARS-CoV-2 that teaches an enveloped virus of SARS-COV-2 as claimed (See Title and Abstract). Chen teaches the base claim 1 a) by stating that the they designed a therapeutic nanoparticle termed ‘‘Nanotrap’’ to inhibit SARS-CoV-2 infection and Nanotrap surfaces were functionalized with either ACE2 recombinant proteins or anti-SARS-CoV-2 neutralizing antibodies with high surface density (See page 2060, paragraph 1), where the ACE2 is the surface exposed cell receptor molecule that mediates entry of an enveloped virus into host cells as taught by Chen at “To gain entry to host cells for infection, SARS-CoV-2 surface spike protein binds to its receptor human angiotensin-converting enzyme 2 (ACE2) with high affinity. Blocking entry of SARS-CoV-2 to host cells is one of the most effective ways to prevent infection (See page 2059, paragraph 3). Also, it is common knowledge in the art that the SARS-COV-2 is an enveloped virus.
For the base claim 1 b), Chen teaches that their Nanotraps completely blocked pseudotyped SARS-CoV-2 entry into susceptible ACE2-overexpressing HEK293T cells, lung epithelial A549 cells, and human primary lung cells, as well as authentic SARS-CoV-2 infection of Vero E6 cells. Furthermore, in vitro cell culture and in vivo intratracheal administration of Nanotraps to immunocompetent mice
demonstrated an excellent biosafety profile. Lastly, the Nanotraps completely inhibited
infection of SARS-CoV-2 pseudovirus in live human lungs maintained under
normothermic physiologic conditions on a clinically applicable ex vivo lung perfusion
(EVLP) system,30,31 confirming the therapeutic efficacy (See page 2060, paragraph 3). In Chen’s Figure 1 (See page 2061 and below), it teaches the design and characterization of the interaction between the Nanotraps and the SARS-COV-2 by blocking the interaction between the spike protein of SARS-CoV-2 and the ACE2 of host cells (See e.g., Abstract).
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Regarding claim 2, Chen teaches that the cell receptor molecule is ACE2 (See e.g., Abstract and Figure 1 above).
Regarding claim 3, Chen teaches the enveloped virus is SRAS-COV-2 (See e.g., Abstract and Title).
Regarding claim 5, Chen teaches that the liposome by stating that “the liposomal-based Nanotrap surfaces were functionalized with either recombinant ACE2 proteins or anti-SARS-CoV-2 neutralizing antibodies and phagocytosis-specific phosphatidylserines” (See Abstract).
Regarding claims 7 and 8, Chen teaches that Nanotraps have the potential to be formulated into a nasal spray or inhaler for easy administration and direct delivery to the respiratory system, as an oral or ocular liquid, or subcutaneous, intramuscular, or intravenous injection to target different sites of SARS-CoV-2 exposure (See Page 2059, Progress and potential). Here the intravenous injection teaches the administration being into circulation system.
Accordingly, Chen teaches each and every aspect of the claims 1-3, 5 and 7-8.
Claim Rejections - 35 USC § 103
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.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Chen as applied to claims 1-3, 5 and 7-8 above in view of Lee et al. (Biomaterials. 2021 Jan; 267:120389. Epub 2020 Oct 23).
Claim 4 requires the nanoparticle further comprises a specific DNA or RNA degrading agent.
Chen teaches that the Nanotrap platform could be further developed into new vaccines and therapeutics against a broad range of diseases by incorporating different small molecule drugs, RNA or DNA (See page 2059, Progress and potential), but Chen does not explicitly teach a DNA or RNA degrading agent.
Lee teaches a long-acting nanoparticulate DNase-1 for effective suppression of SARS-CoV-2-mediated neutrophil activities and cytokine storm. Lee discloses that they generated recombinant DNase-1-coated polydopamine-poly (ethylene glycol) nanoparticulates (named long-acting DNase-1), and their findings suggest that exogenously administered long-acting nanoparticulate DNase-1 can effectively reduce cfDNA levels and neutrophil activities and can be used as a potential therapeutic intervention for life-threatening SARS-CoV-2-mediated illnesses (See Abstract and page 2, left column). The scheme 1 of Lee teaches the preparation of the long-acting nanoparticulate DNase-1 (See page 2, Scheme 1 and below), and the DNAse-1 activity was confirmed using a DNA degradation assay (See page 2, right column, paragraph 3).
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It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to introduce the nanoparticle of long-acting DNase-1 of Lee into to Chen’s study to arrive at an invention as claimed. One of skill in the art would have been motivated to do so because the exogeneous DNase-1 reduced NETosis in the plasma of COVID-19 patients with sepsis. There would be a reasonable expectation of success to develop a method of neutralizing an enveloped virus containing DNA or RNA degrading reagent such DNase-1 as claimed.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Chen as applied to claims 1-3, 5 and 7-8 above in view of Tenchov et al. (ACS Nano. 2021 Nov 23;15(11):16982-17015. Epub 2021 Jun 28).
Claim 6 requires the nanoparticle is unilamellar liposomes.
Chen teaches a liposomal-based Nanotrap/nanoparticle (See Abstract), but Chen does not explicitly teach the unilamellar liposomes.
Tenchov teaches that the liposomes may be either unilamellar (small unilamellar vesicles (SUV) with diameters of 20−100 nm, large unilamellar vesicles (LUV) with diameters of 100−1000 nm, or giant unilamellar vesicles (GUV) with diameters >1000 nm) or multilamellar vesicles (MLV), with diameters of >500 nm, in which concentric bilayers form an onion-like multilayer structure (Figure S1) (See page 16984, left column). Tenchov also teaches that size is a critical parameter in determining liposome drug encapsulation and half-life in circulation, with smaller liposomes having more chances of escaping phagocyte uptake (See page 16984, left column) and discloses that the particle sizes of SLN and NLC vary between 40 and ∼1000 nm (See page 16985, right column, paragraph 1). Although the size range is not identical to the size as claimed at 30 to 500 nm, one of skilled in the art can optimize the size based on the teaching of Tenchov at “The particle size distribution of LNPs can be controlled using manufacturing methods such as extrusion, sonication, and homogenization; more recently, microfluidic methods have been successfully used for LNP manufacture and size control” (See page 16984, right column, paragraph 1).
It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to introduce the unilamellar liposomes and its size of Tenchov into Chen’s study to arrive at an invention as claimed. One of skill in the art would have been motivated to do so because drug delivery systems primarily use SUV and smaller MLV, while GUV are used mainly as models for cells (See page16984). There would be a reasonable expectation of success to develop a method for the unilamellar liposomes as claimed.
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Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Chen as applied to claims 1-3, 5 and 7-8 above in view of Khan et al. (Int J Nanomedicine. 2013; 8:2733-44, Epub 2013 Jul 26).
Claim 9 requires the nanoparticles are administered into the lymphatic circulation of the individual.
Chen teaches that it is reasonable to hypothesize that Nanotraps could be easily formulated into a nasal spray or inhaler for easy administration and direct delivery to the respiratory system, or as an oral or ocular liquid, or subcutaneous, intramuscular, or intravenous injection to target different sites of SARS-CoV-2 exposure, thus offering flexibility in administration (See page 2071, paragraph 5). However, Chen does not specify which route is through the lymphatic circulation.
Nevertheless, khan teaches that the lymphatic route plays an important role in transporting extracellular fluid to maintain homeostasis and in transferring immune cells to injury sites, and is able to avoid first-pass metabolism, thus acting as a bypass route for compounds with lower bioavailability, ie, those undergoing more hepatic metabolism. The lymphatic route also provides an option for the delivery of therapeutic molecules, such as drugs to treat cancer and human immunodeficiency virus, which can travel through the lymphatic system. Two lipid-based nanoformulations, ie, solid lipid nanoparticles and nanostructured lipid carriers, have been administered via multiple routes (subcutaneous, pulmonary, and intestinal) for targeting of the lymphatic system (See Abstract). Khan also discloses the details for the subcutaneous route for lymphatic delivery of SLNs and pulmonary route for lymphatic delivery of SLNs (See page 2736).
It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to combine Chen’s study and Khan’s study to arrive at an invention as claimed. One of skill in the art would have been motivated to do so because Khan teaches the importance and method for lymphatic circulation delivering of the nanoparticles through subcutaneous route. There would be a reasonable expectation of success to develop such a method lymphatic circulation administration as claimed.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Chen as applied to claims 1-3, 5 and 7-8 above in view of Lee et al. (US 2018/0021447 A1, published on Jan. 25, 2018) as evidenced by Agbottah et al. (Virology. 2006 Feb 20;345(2):373-89), and Freeling et al. (AIDS Res Hum Retroviruses. 2015 Jan;31(1):107-14).
Claim 10 requires the method further comprising treating the individual with a second anti-viral therapy.
Chen teaches that Nanotrap platform could be further developed into new vaccines and therapeutics against a broad range of diseases by incorporating different small molecule drugs, RNA, DNA, peptides, recombinant proteins, or antibodies (See page 2059, Progress and potential). At the same time, Chen teaches a neutralizing antibody that can completely blocked SARS-CoV-2 pseudovirus infection (See page 2065, paragraph 3). Thus, one of skilled in the art can incorporate the neutralizing antibody into the Nanotrap functionalized with recombinant ACE2 proteins as a second anti-viral therapy.
Nevertheless, Lee teaches lipid nanoparticle formulations, methods of making, and methods of using same are disclosed (See Abstract) and also discloses that LN formulations may further comprise peptides and/or proteins. peptides and proteins, especially those derived from bacteria and viruses (See [0085]), where the peptides can be selected from rabies virus glycoprotein, HIV-Tat; herpes simplex virus VP22 protein (See [0014]). It is a common knowledge in the art that viral-derived peptides can become powerful anti-viral agents. This can be evidenced by Agbottah’s study. Agbottah teaches that Inhibition of HIV-1 virus replication using small soluble Tat peptides (See title).
Freeling studies the anti-HIV drug-combination nanoparticles enhance plasma drug exposure duration as well as triple-drug combination levels in cells within lymph nodes and blood in primates, and teaches that they developed multidrug anti-HIV lipid nanoparticles (anti-HIV LNPs) containing lopinavir (LPV), ritonavir (RTV), and tenofovir (PMPA). Anti-HIV LNPs incorporated LPV and RTV with high efficiency and entrapped a reproducible fraction of hydrophilic PMPA, and multiple antiretroviral agents can be simultaneously incorporated into anti-HIV lipid nanoparticles to enhance intracellular drug concentrations in blood and lymph nodes, where viral replication persists (See Abstract).
It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings from Chen, Lee and Freeling to arrive at an invention as claimed. One of skill in the art would have been motivated to do so based on the second anti-viral therapy benefit by incorporating anti-viral peptide or anti-viral drug into the nanoparticles taught by Lee and Freeling. There would be a reasonable expectation of success to develop such a method comprising treating the individual with a second anti-viral therapy.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RUIXUE WANG whose telephone number is (571)272-7960. The examiner can normally be reached Monday-Friday 8:00 am to 4:30 pm, EST.
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/RUIXUE WANG/ Examiner, Art Unit 1672
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