DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of invention I and the required species in the reply filed on 6/9/26 is acknowledged.
Applicants did traverse the species election requirement submitted on 7/13/26. They argue that the number of species listed are limited and would not impose a serious search burden. In response, the species election requirement has been considered and therefore is withdrawn. As a result, the species elected for examination by the Examiner are “non-antibody protein” found in claim 2 and “retroviridae” found in claim 6.
Claims 14-20 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6/9/26.
Claims 1-13 are examined on the merits.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/15/23 and 11/13/25 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
From Paragraph 11: In some embodiments, the method includes preparing a process solution
including a target drug of interest and a plurality of viral surrogate nanoparticles configured to
mimic the size, shape, net charge, hydrophobicity, or combinations thereof, of a target live virus
equivalent.
Claim Rejections - 35 USC § 112
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 1-13 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites, “a viral surface-mimicking layer on a surface of the core, wherein the viral surface-mimicking layer physicochemically mimics an external surface of a target live virus equivalent, wherein the viral surface-mimicking layer includes:”. However, it is unclear what the metes and bounds of a target live virus equivalent are since the claim nor the specification provide a definition or specific example as to what is included and what is excluded for an equivalent to be identified. Is the equivalent a functional equivalent or a homologous live virus, such as a virus from the same family? Moreover, it is unclear what the metes and bounds of mimicking the physicochemical external surface are since the target live virus equivalent is not defined and the external surface of viruses contain more than one external component, see figure 47.3 below. Furthermore, given the unclear limitations pertaining to the target live virus equivalent, it is unclear what the metes and bounds of “a viral surface-mimicking layer” are and what a “viral surrogate nanoparticles” are. Does mimicking require that the viral surface layer be identical to a naturally occurring virus or only share some components from the surface of a naturally occurring virus. This also applies to what constitutes a viral surrogate nanoparticle. These limitations are also recited in claims 4, 5, 10 and 11. Furthermore, claim 1 recites, “the surfaces being configured to bind the viral surface-mimicking layer of the viral surrogate nanoparticles”. However, it is unclear how the surfaces can be configured to bind to the viral surface-mimicking layer since such a layer is not clearly defined by the claims nor the specification.
Claim 4 indicates that viral surrogate nanoparticles mimic the size, shape, net charge, hydrophobicity or combinations thereof of the target live virus equivalent. If the viral surface-mimicking layer involves attaching capsid proteins to a core, it is unclear how the viral surrogate nanoparticles can mimic the surface of the virus, but also mimic the size, shape, net charge hydrophobicity or combinations thereof, relative to the target live virus equivalent, which as discussed above, is indefinite.
Claim 10 requires that the substrate bears a net charge opposite of the viral surrogate nanoparticles, however, in view of the unclear metes and bounds of the viral surrogate nanoparticles, it is also unclear what the net charge would be opposite to in order for the substrate to bind these nanoparticles.
Claims 2-13 are also rejected because they depend from claim 1 but do not remedy this deficiency.
Claim 6 recites, “The system according to claim 1, wherein the one or more capsid or capsid-like proteins are from a family including retroviridae.” Claim 1 recites, “a viral surface-mimicking layer includes: one or more capsid or capsid-like proteins of the target live virus equivalent…” However, viruses of the retroviridae family, such as HIV, do not possess capsid proteins which would mimic the viral surface layer. HIV is an enveloped virus, which possesses a lipid bilayer and external proteins that are presented there upon. HIV does possess a capsid, however, it is within the matrix of the virus and not present on the surface of the virus [see figure 47.3 below, sourced from Fields Virology, 2013, 6th Edition]. Therefore, using capsid proteins from a retrovirus would not generate a viral surface mimicking layer. It is therefore unclear if the claim requires capsid proteins or not.
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Claim 11 recites, “The system according to claim 1, further comprising a fluorescence emission spectrophotometer positioned to identify a fluorescent signal from viral surrogate nanoparticles on the membrane separator for conversion to a viral surrogate nanoparticle concentration value via a standard curve.” However, the core possess the fluorescent material and therefore, it is unclear how a concentration value of a viral surrogate nanoparticle can be determined when core particles lacking bound viral components would also be detected by the emission spectrophotometer, thereby providing a false positive signal.
Claim 13 recites, “one or more capsid or capsid-like proteins cover about 55% of the surface of the core”. However, it is unclear what the metes and bounds of “about 55%” are since about is not defined by the specification to have an upper and lower limit. Furthermore, what constitutes a “capsid-like protein”. Does a capsid-like protein possess a homologous function to a capsid protein, or a shared motif or a share amino acid sequence. What are the metes and bounds of a “capsid-like protein”? This indefiniteness also applies to the same limitation present in claim 1.
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.
Claim(s) 1-10, 12 and 13 are rejected under 35 U.S.C. 102a1 as being anticipated by Albrecht et al. (US PGPub 20090214663).
The claimed invention recites an intended use “for quantifying virus concentration of a viral clearance sample”. MPEP 2111.02 provides guidance pertaining to intended use limitations and how such limitations do not carry patentable weight.
The claimed invention is drawn to a system for quantifying virus concentration of a viral clearance sample, comprising:
a process solution including a target drug of interest;
a plurality of viral surrogate nanoparticles, the particles including: a core including one or more fluorescent materials; and a viral surface-mimicking layer on a surface of the core, wherein the viral surface-mimicking layer physicochemically mimics an external surface of a target live virus equivalent, wherein the viral surface-mimicking layer includes: one or more capsid or capsid-like proteins of the target live virus equivalent directly associated with: the core; a lipid bilayer attached to the core, or combinations thereof;
a membrane separator in fluid communication with the process solution, the membrane separator including: a polycarbonate substrate having a plurality of pores extending therethrough; and one or more surfaces on the substrate, the surfaces being configured to bind the viral surface-mimicking layer of the viral surrogate nanoparticles.
Wherein the target drug of interest includes non-antibody protein,
Wherein the core includes one or more polymers including polystyrene, polystyrene copolymers, or combinations thereof.
Wherein the viral surrogate nanoparticles mimic the size, shape, net charge, hydrophobicity, or combinations thereof, of the target live virus equivalent.
Wherein the cores include one or more additional chemical treatments to the surface of the core after primary surface modification, the additional chemical treatments configured further improve physicochemical mimicking of the target live virus equivalent by the viral surrogate nanoparticles.
Wherein the one or more capsid or capsid-like proteins are from a family including Retroviridae or a Herpesviridae.
Wherein a lipid bilayer containing embedded viral envelope proteins is attached to the core via one or more lipid anchors.
Wherein the core has a diameter between about 20nm and about 200nm and the pore size of the membrane separator is 50nm or about 200 nm.
Wherein the one or more surfaces on the substrate: bears a net charge opposite of the viral surrogate nanoparticles; or
includes one or more moieties that: promote binding of the viral surrogate nanoparticles to the membrane separator;
bear a net charge opposite of the viral surrogate nanoparticles; or combinations thereof.
Wherein said process solution is produced from a cell culture process, a fermentation process, or combinations thereof.
Wherein the one or more capsid or capsid-like proteins cover about 55% of the surface of the core.
The Prior Art
Albrecht et al. teach at paragraph 55, “The present invention is also directed to a method of generating the viral envelope coated core particle discussed supra, comprising: lysing an intact virus via osmotic shock, sonicating membrane of the virus to dissociate viral envelope and nucleocapsid of the virus, separating the viral envelope and the nucleocapsid of the virus using a density gradient, incubating the viral envelope and the core particle for at least fifteen minutes, sonicating the viral envelope/core particle mixture to dissociate envelope vesicle aggregates and to permit association of the envelope with the core particle and passing the virus envelope/core particle mixture through an extruder with a defined pre size of 50 to about 200 nm such that the passage through the filter and pressure applied during the passage forces the membrane of the virus to be extruded over the core particle, thereby generating the viral envelope coated core particle. This method may further comprise attaching a fluorescent label to the viral envelope coated core particle. This method may also further comprise loading the viral envelope coated core particle with a protein of a pathogen, a modified protein of the pathogen, a nucleic acid or a nucleic acid like molecule encoding an immunogenic peptide, an antigen or an inhibitory RNA, a protein, a probe or a therapeutic agent. Examples of the therapeutic agent are the same as discussed supra.”
Therefore, Albrecht et al. teach a process solution containing non-antibody proteins (a protein of a pathogen or a modified protein of a pathogen), a plurality viral surrogate nanoparticles that possess a core and viral enveloped proteins coated thereon and a membrane filter (separator) using a 2uM polycarbonate filter [see paragraphs 16 and 67] Albrecht et al. further teach that the core particles can be 100nm in diameter and are fluorescently labeled [see paragraph 65] The present invention does not specify what or how the surface of the polycarbonate substrate have been configured to bind the viral surface mimicking layer of the nanoparticles, therefore, by Albrecht et al. teaching the use of polycarbonate membrane with pores for obtaining the viral envelope coated core particles, their polycarbonate membrane appears to have been configured to bind. Therefore, the core particle contains about 55% of envelope proteins (capsid proteins). Albrecht et al. further teach that the core particle can be polystyrene particle and the core particles can be at least 100nm in diameter. [see claim 8 and paragraph 54] Furthermore, examples of the viral envelope can be from a retrovirus, such as Moloney murine leukemia virus (Mo-MLV) or HIV. [see paragraph 54] Since Albrecht et al. teach viral envelope coated core particles, they would possess the net charge of the target live virus equivalent and Albrect et al. teach that the lipid bilayer of at least their Mo-MLV coated core particle possess the viral lipid bilayer, thereby anchoring the viral envelope proteins via a lipid anchor to the core. [see paragraph 76] Albrecht et al. teach the isolation of MoMLV from cell cultures. [see paragraph 64]
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BENJAMIN P BLUMEL whose telephone number is (571)272-4960. The examiner can normally be reached M-F 8-5 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Allen can be reached at (571) 270-3497. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BENJAMIN P BLUMEL/Primary Examiner, Art Unit 1671
