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
Claim Status
Claims 1-16 are under consideration.
Priority
Priority to provisional application 63/464,358 with a filing date of 05/05/2023 is acknowledged.
Information Disclosure Statement
It is noted that Applicants have not filed an information disclosure statement under § 1.97(c). Applicant is reminded of 37 CFR § 1.56, which details Applicant’s duty to disclose all information known to be material to patentability.
Claim Objections
Claims 14, 15 are objected to because of the following informalities:
Claim 14: Add “the” between “treat” and “infection”. For example, “composition in an amount effective to treat the infection by the enveloped virus”.
Claim 15: Add “the” between “treat” and “infection”. For example, ““composition in an amount effective to treat the infection by the enveloped virus”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1-3, 4-16 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
See claims 1-3, 4-16 as submitted 05/03/2024.
Claims 1 recites a truncated form of a viral envelope protein displayed on the VLP, the truncated form comprising a deletion of at least a portion of a cytoplasmic tail region of the envelope protein. Claims 2 and 3 are dependent on claim 1. Claim 2 further limits with the VLP comprising an HIV-1 Gag, and the truncated form of the viral envelope protein comprising an HIV-1 envelope. Claim 3 adds an adjuvant. Claims 4, 6, 8, 14, and 15 recite a polynucleotide encoding a viral envelope protein comprising a deletion of at least a portion of a cytoplasmic tail. The problematic clause of all of the claims is “at least a portion of a cytoplasmic tail region of the envelope protein” particularly when only the HIV-1 envelope was provided as an example while details about other envelope viruses have not been provided.
The following quotation from section 2163 of the Manual of Patent Examination
Procedure is a brief discussion of what is required in a specification to satisfy the 35 U.S.C. 112 written description requirement for a generic claim covering several distinct inventions:
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. 'A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
Thus, when a claim covers a genus of inventions, the specification must provide written description support for the entire scope of the genus. Support for a genus is generally found where the applicant has provided a number of examples sufficient so that one in the art would recognize from the specification the scope of what is being claimed.
In the present case, the specification focuses on the embodiment with the HIV-1 envelope but does not elaborate on any other enveloped virus, to include virus identification, length of the respective cytoplasmic tail region, reference sequences of the cytoplasmic tail region or amino acid/nucleotide deletion positions relative to a particular reference sequence.
As to the state of the art, White et al. (White)(See PTO-892 Notice of References Cited) teaches “Virus-cell fusion is the means by which all enveloped viruses, including devastating human pathogens such as human immunodeficiency virus (HIV) and Ebola virus, enter cells and initiate disease-causing cycles of replication. In all cases virus-cell fusion is executed by one or more viral surface glycoproteins, including one that is generally denoted as the fusion protein. Certain viral fusion proteins induce cell-cell fusion when expressed on the cell surface as a consequence of infection, and cell-cell fusion can contribute to viral spread, virulence, persistence, and other untoward consequences (p. 1). White also teaches “[d]espite the existence of many common features among viral fusion proteins (common pathway of membrane dynamics, common prehairpin and trimer-of-hairpins conformations), viral fusion proteins differ in several important respects (Tables 1 and 2). They vary in terms of their detailed structures, how they are triggered, and the number of different viral surface proteins involved. These and other differences combine to yield a rich diversity of fusion proteins (Figure 2). Apparently diverse proteins have converged on a common mechanism (Figure 1A) to merge lipid bilayers” (p. 3). With respect to cytoplasmic tails (CTs), White teaches the cytoplasmic tails (CTs) of viral fusion proteins have a variety of functions that differ both among and within virus families. Furthermore, results are often difficult to interpret because alterations in the CT can affect stability, surface expression, membrane domain localization, and virion incorporation of the fusion protein. Nevertheless, the CTs of many fusion proteins have direct effects on fusion (p. 22).
The specification teaches one exemplary HIV-1 envelope protein truncation such as amino acid 1-709 of SEQ ID NO: 1, etc. (p. 6-12) but in totality, does not identify a representative sample of other envelope viruses or provide specifics as to the deletions of at least a portion of a cytoplasmic tail for the different viruses as claimed, nor provide additional information on the structure-function impact that the deletions have, ultimately, on fusion.
For the reasons above, and in view of the uncertainty as to the effects of the deletions, which are unspecified in the claim set, the application therefore fails to provide adequate support for the composition and the methods of using this genus.
Claims 14-16 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 method of treating involving a HIV-1 envelope protein in a truncated form, does not reasonably provide enablement for other viruses and their envelope protein in a truncated form. 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.
See claims 14-16 as submitted 05/03/2024.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.” These factors include, but are not limited to:
(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.
In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
Here, the instant claims are broadly drawn to a method of treating a subject having or at risk of having, an infection by an enveloped virus (as recited in claims 14 and 15). Claim 14’s method comprises a VLP and a truncated form of a viral envelope protein displayed on the VLP, the truncated form comprising a deletion of at least a portion of a cytoplasmic tail region of the envelope protein. Claim 15’s method comprises a first polynucleotide encoding a VLP subunit protein, a second polynucleotide encoding a viral envelope protein comprising a deletion of at least a portion of a cytoplasmic tail, and a delivery vehicle attached to or encapsulating the first polynucleotide and the second polynucleotide.
The level of skill in the art is high and would include, e.g., Ph.D. level scientists and physicians. As previously mentioned, White teaches the cytoplasmic tails (CTs) of viral fusion proteins have a variety of functions that differ both among and within virus families. Furthermore, results are often difficult to interpret because alterations in the CT can affect stability, surface expression, membrane domain localization, and virion incorporation of the fusion protein. Nevertheless, the CTs of many fusion proteins have direct effects on fusion (p. 22). As such, there is no predictability for the treatment of all viral infections with a causative agent being an envelope virus.
The Specification only exemplified and reduces to practice constructs and experimental examples for HIV-1. The Specification offers no working examples or direction for treating other enveloped virus-related infections/diseases in any subject or subjects “at risk” through administration of the claimed composition in claims 14 and 15.
In view of the foregoing, a vast quantity of experimentation, including extensive animal/clinical trials with pertinent subjects - human and non-human as identified in the Specification on pages 15-16 – would be required to use the invention based on the content of the disclosure.
Taken together, 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 the claims.
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 4-8 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.
See claims 4-8 as submitted 05/03/2024.
Claim 4: The significance of “first” and “second” designations for the polynucleotide encoding the VLP or the viral envelope protein is unclear and their relationship with each other based on the “first” and “second” designations is unclear for this claim. For example, it is unclear if first and second denote an order within the open reading frame. Claim 5 is rejected as it is dependent on claim 4.
Claim 6: The significance of “first delivery” and “second delivery” vehicle designations for the “first and second” polynucleotides are unclear. It is unclear if the claim is implying a stepwise method for, for example, transfecting a cell. It is also unclear if the claim is implying that the first delivery vehicle and the second delivery vehicle should be different or if they can be the same. For compact prosecution purposes, the first and second delivery vehicles can be the same type of delivery vehicle but that the first polynucleotide would have its own delivery vehicle and the second polynucleotide would have its own delivery vehicle. Claim 7 is rejected as it is dependent on claim 6.
Claim 8: With respect to the language “allowing the cell”, “allowing the VLP”, it is unclear what is meant by “allowing”. It is unclear if there are additional steps, parameters or a time element required or not.
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.
Claims 1 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Amara et al. (Amara)(WO2021097254A1)(See PTO-892 Notice of References Cited).
See claims 1 and 14 as submitted 05/03/2024.
Regarding claim 1 and 14, Amara, however, teaches VLPs (p. 6) and HIV-1 envelope proteins (p. 5) or envelope protein fragments, or trimeric complexes thereof which have uses in vaccination methods or therapeutic strategies. Amara teaches the modified HIV envelope protein is derived from “different HIV-1 strains or subtypes…In various embodiments, the C terminus of the modified HIV envelope protein can be truncated to either residue 664 or 681 (according to HXB2 nomenclature), resulting in the gpl40 versions like "BG505 SOSIP.gpl40.664" and "BG505 SOSIP.gpl40.681" which are known in the art” (as recited in instant claim 1, “at least a portion of the cytoplasmic tail deleted”)(p.25). Amara also teaches “In certain embodiments, it is contemplated that modified HIV envelope proteins, fragments, and trimeric complexes comprising the same as disclosed herein are presented on nanoparticles and virus like particle, e.g., constructs that are expressed wherein the C-terminus of an HIV envelope protein is fused to the N-terminus of ferritin subunit to form nanoparticles…In certain embodiments, it is contemplated that modified HIV envelope proteins trimer can include modifications, such as amino acid substitutions, deletions or insertions, glycosylation and/or covalent linkage to unrelated proteins (e.g., a protein tag), as long as the modified HIV envelope proteins can form the trimer”(p. 26).
Regarding claim 14, Amara teaches “In certain embodiments, this disclosure relates to methods of vaccinating for HIV comprising administering an effective amount of a protein disclosed herein or fragment thereof, a trimeric protein complex comprising the protein or fragment, a particle comprising the trimeric complex, or a vector encoding the protein, to a subject (as recited in instant claim 14, “or at risk of having”). Amara also teaches “In certain embodiments, this disclosure relates to methods of treating a subject with an HIV infection comprising administering an effective amount of a protein disclosed herein or fragment, a trimeric protein complex comprising the protein or fragment, a particle comprising a trimeric complex, or a vector encoding the protein to a subject in need thereof” (as recited in instant claim 14, “having…and infection”)(p. 4).
In view of the foregoing, all the claimed limitations are found in one reference and are taught to be optional variations to a base product and process they exemplify. As such, the claimed product and process recited in claims 1 and 14, is within the scope of Amara’s invention, and thus Amara’s invention renders claims 1 and 14 prima facie obvious. The rationale to support this conclusion of obviousness is that Amara provides a teaching, suggestion, and motivation to substitute different variables disclosed within the reference. Furthermore, there is no evidence on the record that indicates that the claimed product and process exhibit any unexpected results compared to the prior art.
Claims 2-3 are rejected under 35 U.S.C. 103 as being unpatentable over Amara, as applied to claim 1, and further in view of Costa Fejoz et al. (Costa Fejoz)(EP4151737A1)(See PTO-892 Notice of References Cited).
See claims 2-3 as submitted 05/03/2024.
Amara teaches claim 1.
Regarding claim 2, Amara also teaches claim 2 – HIV-1 envelope protein with at least a portion of the cytoplasmic tail deleted. Amara does not specifically teach the VLP comprises HIV-1 Gag.
Regarding claim 2, Costa Fejoz, however, teaches in a preferred embodiment, said retrovirus is a lentivirus, more preferably HIV-1 or HIV-2. Costa Fejoz also teaches “the origin of the gag and pol genes gives its name to the retrovirus-like particle or retroviral vector. For instance, the expression "HIV-1-derived retrovirus-like particle or retroviral vector" usually indicates that the gag and pol genes are those of HIV-1 or are modified gag and pol genes from HIV-1” (as recited in instant claim 2, “VLP comprises HIV-1 Gag).
Regarding claim 3, Amara also teaches “For vaccine compositions, appropriate adjuvants can be additionally included. Examples of suitable adjuvants include, e.g., aluminum hydroxide, lecithin, Freund's adjuvant, MPL™ and IL-12. In some embodiments, the HIV-1 immunogens disclosed herein can be formulated as a controlled-release or time-release formulation” (p. 33).
One of ordinary skill in the art would have been motivated to combine the teachings of Amara - the VLP, truncated HIV-1 envelope protein - with the more specific teachings of Costa Fejoz – “HIV-1-derived retrovirus-like particle or retroviral vector and corresponding HIV-1 Gag” - to increase the likelihood and accuracy of VLP generation but with a modified HIV-1 envelope protein by using the same retrovirus derived components (See MPEP 2143, Rationale A. Combining prior art elements according to known methods to yield predictable results).
One of ordinary skill in the art would have had a reasonable expectation of success for using the HIV-1 Gag as taught by Costa Fejoz. There would have been a reasonable expectation of success given the underlying materials and methods are known, successfully demonstrated in the context of molecular biology, therapeutics, and/or immunity, and commonly used as evidenced by the applied prior art.
Therefore, the invention as a whole would have been prima facie obvious to one of
ordinary skill in the art before the effective filing date of the claimed invention.
Claims 4, 5, 6, 7, 15, 16 are rejected under 35 U.S.C. 103 as being unpatentable over Amara et al. (Amara)(See PTO-892 Notice of References Cited) in view of Zhang et al. (Zhang)(WO2021055855A1)(See PTO-892 Notice of References Cited).
See claims 4, 5, 6, 7, 15, 16 as submitted 05/03/2024.
Regarding claim 4, Amara teaches “In certain embodiments, this disclosure contemplates pharmaceutical compositions containing HIV-1 immunogens e.g., soluble modified HIV envelope proteins, fragments, trimeric complexes or nanoparticles displaying an Env-derived trimer, as well as polynucleotides encoding the proteins described herein for preventing and treating HIV-1 infections” (p.30). Amara also teaches VLPs and a truncated viral envelope protein as discussed previously.
Regarding claim 15, Amara teaches “In certain embodiments, this disclosure relates to methods of vaccinating for HIV comprising administering an effective amount of a protein disclosed herein or fragment thereof, a trimeric protein complex comprising the protein or fragment, a particle comprising the trimeric complex, or a vector encoding the protein, to a subject” (p. 4). Amara also teaches “In certain embodiments, this disclosure relates to methods of treating a subject with an HIV infection comprising administering an effective amount of a protein disclosed herein or fragment, a trimeric protein complex comprising the protein or fragment, a particle comprising a trimeric complex, or a vector encoding the protein to a subject in need thereof” (p. 4).
Amara does not specifically teach a delivery vehicle attached to or encapsulating the first polynucleotide and the second polynucleotide together or separately.
Regarding claims 4, 5, 7, 16, Zhang, however, teaches reference claim 1 - An engineered delivery system comprising one or more polynucleotides encoding one or more endogenous retroviral elements for forming a delivery vesicle and one or more capture moieties for packaging a cargo within the delivery vesicle – and teaches reference claim 2 - The system of claim 1, wherein the one or more endogenous retroviral elements for forming a delivery vesicle comprises two or more of a retroviral gag protein, a retroviral envelope protein, a retroviral reverse transcriptase or a combination thereof (as recited in instant claim 4). Reference claim 2’s “two” is being interpreted as a retroviral gag protein and a retroviral envelope protein. Zhang further teaches reference claim 36 - The system of any of claims 1 to 35, wherein the delivery vesicle is a virus-like particle as well as teaches the invention also provides delivery vesicles for delivery of the polynucleotides encoding the endogenous proteins. Such delivery vesicles or systems within the scope of the present invention may be provided in any form, including but not limited to solid, semi-solid, emulsion, or colloidal particles. As such, any of the delivery systems described herein, including but not limited to, e.g., lipid-based systems, liposomes, micelles, microvesicles, exosomes, or gene gun may be provided as particle delivery systems within the scope of the present invention [0134] (reads on claims 5, 7 and 16, “lipid nanoparticle”).
Regarding claim 6, Zhang also teaches “in another aspect, the invention provides a delivery vesicle comprising one or more components encoded in the one or more polynucleotides in the engineered delivery system described herein [0022]. It follows then that one of the components could be a “VLP subunit protein”, encoded by a polynucleotide and encapsulated by a delivery vesicle. And similarly, one of the components could be truncated “viral envelope protein”, encoded by a polynucleotide, and encapsulated by a separate delivery vesicle.
One of ordinary skill in the art would have been motivated to combine the teachings of Amara (VLP, truncated envelope protein, polynucleotides, and nanoparticles) with the teachings of Zhang (polynucleotides encoding one or more endogenous retroviral elements, VLP, lipid nanoparticle delivery vehicles) in order to design a therapeutic composition, particularly one used for the treatment of a retrovirus infection, for direct delivery to infected cells or as a prophylactic, to uninfected cells (See MPEP 2143, Rationale A. Combining prior art elements according to known methods yield predictable results).
One of ordinary skill in the art would have had a reasonable expectation of success for combining the teachings of Amara and Zhang. There would have been a reasonable expectation of success given the underlying materials and methods are known, successfully demonstrated in the context of molecular biology, therapeutics, and/or immunity, and commonly used as evidenced by the applied prior art.
Therefore, the invention as a whole would have been prima facie obvious to one of
ordinary skill in the art before the effective filing date of the claimed invention.
Claim 8, 9, 12, and 13 is rejected under 35 U.S.C. 103 as being unpatentable over Amara in view of Zhang and Doan et al (Doan)(See PTO-892 Notice of References Cited).
See claims 8, 9, 12 and 13 as submitted 05/03/2024.
Regarding claim 8, Amara teaches “In certain embodiments, this disclosure contemplates pharmaceutical compositions containing HIV-1 immunogens e.g., soluble modified HIV envelope proteins, fragments, trimeric complexes or nanoparticles displaying an Env-derived trimer, as well as polynucleotides encoding the proteins described herein for preventing and treating HIV-1 infections. Amara also teaches VLPs and a truncated viral envelope protein as discussed previously. Thus, Amara teaches aspects of the constructs.
Amara does not describe the method of preparing a VLP-based vaccine.
Regarding claim 8, Zhang teaches reference claim 1 - An engineered delivery system comprising one or more polynucleotides encoding one or more endogenous retroviral elements for forming a delivery vesicle and one or more capture moieties for packaging a cargo within the delivery vesicle – and teaches reference claim 2 - The system of claim 1, wherein the one or more endogenous retroviral elements for forming a delivery vesicle comprises two or more of a retroviral gag protein, a retroviral envelope protein, a retroviral reverse transcriptase or a combination thereof.
Regarding claim 13, Zhang teaches lipid nanoparticles.
Similarly, Zhang also does not describe the method of preparing a VLP-based vaccine.
Doan, however, teaches the baculovirus expression system (pp. 77, 79).
Regarding claim 8, 9, and 12, and in the context of the baculovirus expression system, Doan teaches Sf9 cells from Spodoptera frugiperda are infected at high multiplicity of infection (m.o.i. of 5–10) with separate baculovirus recombinants (as recited in instant claim 8, “transfecting a cell”; as recited in instant claim 9, “cell is transfected in vitro”; as recited in claim 12, “transfected with the first polynucleotide and the second polynucleotide separately”). Each baculovirus recombinant may be constructed to encode the different components necessary for generating the VLP (as recited in instant claim 8, “assemble into a VLP”), such as the Gag capsid protein of HIV-1 and/or Env of HIV, depending on the requirements for the successful assembly of VLPs. In the case of HIV-1, VLPs are released into the media, which can be collected and isolated by ultracentrifugation. Doan also teaches “Using basic principles for generating separate HIV and SIV VLPs as discussed previously, chimeric SHIV VLPs have been produced in insect cells from two recombinant baculoviruses containing the SIVmac239 gag and either full-length or truncated HIV-1 BH10 env or HIV-1 89.6 env protein constructs (Figure 1) [56]. HIV-1 89.6 is a T cell tropic and macrophage tropic primary isolate, whereas HIV-1 BH10 is a lymphotropic strain. The expression levels of Env protein are higher with truncated Env (20%–50%) in both HIV-1 strains. Immunoelectron microscopy has demonstrated the incorporation of Env on the surface of VLPs (as recited in instant claim 8, “truncated viral envelope protein is displayed on the surface of the VLP”) (p. 79).
One of ordinary skill in the art would have been motivated to combine the teachings of Amara and Zhang for the polynucleotide constructs, including a lipid nanoparticle as a delivery vehicle, with the methods of preparing a VLP, particularly the baculovirus expression system as taught by Doan in order to generate virus-like proteins with the truncated viral envelope protein displayed on the surface of the VLP. The resulting VLP would be beneficial as a potential treatment for infections cause by the virus whose envelope protein is on the surface of the VLP (See MPEP 2143, Rationale A. Combining prior art elements according to known methods to yield predictable results and Rationale G. Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention).
One of ordinary skill in the art would have had a reasonable expectation of success for combining the teachings of Amara and Zhang for the polynucleotide constructs with the methods of preparing a VLP, particularly the baculovirus expression system as taught by Doan in order to generate virus-like proteins with the truncated viral envelope protein displayed on the surface of the VLP. There would have been a reasonable expectation of success given the underlying materials and methods are known, successfully demonstrated in the context of molecular biology, therapeutics and/or immunity, and commonly used as evidenced by the applied prior art.
Therefore, the invention as a whole would have been prima facie obvious to one of
ordinary skill in the art before the effective filing date of the claimed invention.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Amara in view of Zhang and Doan as applied to claims 8, 9, 12, and 13 above, and further in view of Barnett et al. (Barnett)(US20080261271A1)(See PTO-892 Notice of References Cited).
See claim 10 as submitted 05/03/2024.
Amara, Zhang and Doan teach claim 8 but do not teach wherein the cell is transfected in vivo.
Barnett, however, teaches the efficient expression of HIV polypeptides in a variety of cell types, including, but not limited to, mammalian, insect, and plant cells. Synthetic expression cassettes encoding the HIV Gag-containing polypeptides are described, as are uses of the expression cassettes in applications including DNA immunization, generation of packaging cell lines, and production of Env-, tat- or Gag-containing proteins. The invention provides methods of producing Virus-Like Particles (VLPs), as well as, uses of the VLPs including, but not limited to, vehicles for the presentation of antigens and stimulation of immune response in subjects to whom the VLPs are administered. Barnett also teaches “the invention further includes a method of generating an immune response in a subject, where cells of a subject are transfected with any of the above-described gene delivery vectors (e.g., alphavirus constructs; alphavirus cDNA constructs; eukaryotic layered vector initiation systems…alphavirus particle preparations…under conditions that permit the expression of a selected polynucleotide and production of a polypeptide of interest (i.e., encoded by any expression cassette of the present invention), thereby eliciting an immunological response to the polypeptide. Transfection of the cells may be performed ex vivo and the transfected cells are reintroduced into the subject. Alternately, or in addition, the cells may be transfected in vivo in the subject. The immune response may be humoral and/or cell-mediated (cellular)[0028].
One of ordinary skill in the art would have been motivated to transfect the cell in vivo as taught by Barnett for targeted cell expression of a therapeutic VLP and for the generation of an immune response (See MPEP2143, Rationale B. Simple substitution of one known element for another to obtain predictable results and Rationale G. Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention).
One of ordinary skill in the art would have had a reasonable expectation of success for transfecting the cells in vivo, by for example, gene therapy, as taught by Barnett. There would have been a reasonable expectation of success given the underlying materials and methods are known, successfully demonstrated in the context of gene therapeutics, molecular biology, and/or immunity, and commonly used as evidenced by the applied prior art.
Therefore, the invention as a whole would have been prima facie obvious to one of
ordinary skill in the art before the effective filing date of the claimed invention.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Amara in view of Zhang and Doan as applied to claims 8, 9, 12, and 13 above, and further in view of Benen et al. (Benen)(See PTO-892 Notice of References Cited).
See claim 11 as submitted 05/03/2024.
Amara, Zhang and Doan teach claim 8 but do not teach wherein the cell is transfected with the first polynucleotide and the second polynucleotide simultaneously.
Benen, however, teaches novel immunogens based on HIV-1 gp41 MPER which combine the above-mentioned criteria. For this purpose, variants of truncated gp41 proteins consisting of CHR, MPER and TM regions were designed and characterized. Heterologous peptide sequences were fused for intracellular trafficking and efficient trimerization. The immunogens were designed to strongly expose the MPER with binding sites to known bnMAbs in a natural conformation and membrane environment. Plasmid DNA and pseudotyped virus-like particles (VLPs) were chosen as immunization vehicles in a rabbit model. After a DNA prime and VLP boost regimen, the presence of anti-MPER Abs and neutralizing activity in unfractionated sera was analyzed (p.2). Benen also teaches VLP production, in that VLPs for immunization purposes were produced in 293 F cells with the use of a codon-optimized, Rev-independent gene for Gag(IIIB)…For pseudotyped VLPs, plasmids encoding for Gag and Env were mixed in a ratio of 2:1 in a co-transfection assay (as recited in claim 11, “simultaneously”).
One of ordinary skill in the art would have been motivated to co-transfect cells with the first polynucleotide and the second polynucleotide simultaneously or via co-transfection as taught by Benen in order to achieve simultaneous expression of both viral proteins in a single host cell which then drives the spontaneous, self-assembly of complex, multi-protein VLPs and potentially maximize antigen yield (See MPEP 2143, Rational B. Simple substitution of one known element for another to obtain predictable results).
One of ordinary skill in the art would have had a reasonable expectation of success for transfecting the cells in vivo, by for example, gene therapy, as taught by Benen. There would have been a reasonable expectation of success given the underlying materials and methods are known, successfully demonstrated in the context of gene therapeutics, molecular biology and/or immunity, and commonly used as evidenced by the applied prior art.
Therefore, the invention as a whole would have been prima facie obvious to one of
ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
With respect to 35 U.S.C. 101, and in view of the 35 U.S.C. 112(b) rejection above, the “allowing” step in claim 8 is interpreted to read on post-transfection, the cell(s) expressing the polynucleotides and the VLP subunits and the truncated viral protein to assemble without any other intervention or additional consideration.
No claims allowed.
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/C.C./Examiner, Art Unit 1672
/M FRANCO G SALVOZA/Primary Examiner, Art Unit 1672
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