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 the required species in the reply filed on 10/13/2025 is acknowledged. The elected species is that of SEQ ID NO: 1.
Claims 8-11 and 16 are withdrawn from consideration as they recite non-elected species.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 5/24/23, 4/12/24, 5/21/24, 7/16/25, 7/23/25, 8/8/25 and 11/25/25 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
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, 14, 17, 23-27 and 53 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 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 requirements 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.
Claims 1-3, 14, 17, 23-27 and 53 are rejected as lacking adequate descriptive support for a generating a polypeptide comprising or consisting of: (a) an amino acid sequence at least 75% identical to the amino acid sequence of SEQ ID NO:1, wherein 1, 2, 3, 4, 5, 6, 7, 8, 9, or all 10 of the following mutations relative to SEQ ID NO:1 are present in the polypeptide: F32Y, H37D/E/K/N/Q/R, F43Q, F168D/E/K/N/Q/R/S/T/Y, K169D/E/N/Q, L173D/E/N/Q/S, A174S, S179D/E, K183D/E, and/or T185D/E/K/N/Q/S.
Furthermore, SEQ ID NO:s 7-14 represent mutated versions of SEQ ID NO: 1, but based on the sequence listing on file, amino acids 1-26 and 230-244 or 1-21 and 225-239 can be absent.
The claimed polypeptide of SEQ ID NO: 1 inherently possesses the ability to self- assemble into a nanoparticle (see claim 17) and the claimed polypeptide is part of a fusion protein with a second functional peptide (see claim 14).
Further, while the claims provide both a structure and a function, the application fails to draw any correlation between the two. I.e., there is no evidence that any mutant of claim 1 (as it requires SEQ ID NO: 1) can still retain the ability of forming a nanoparticle or the second functional protein of claim 14 can also achieve this nanoparticle formation. Moreover, no correlation has been made to which portion of SEQ ID NO: 1 is required in order to maintain an ability to function as a nanoparticle forming polypeptide. Lastly, the specification states that SEQ ID NO: 1 was able to form nanoparticles, but mutants of SEQ ID NO: 1 needed assistance with a “second component” to form these nanoparticles (see Section F on page 21 of the specification.
Thus, in view of the above, there would have been significant uncertainty as to which mutants of the SEQ ID NO: 1 with or without a generic second functional protein, would be able form nanoparticles. In view of this uncertainty and the lack of any examples of the claimed genus, the claims are rejected for lack of adequate written description support.
Claims 24, 25, 26, 48, 50 and 51 are rejected under 35 U.S.C. 112, first paragraph, as containing subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Applicant broadly claims a host cell or expression vector or nucleic acid containing the nucleic acids of claims 24, 25, 26, 48, 50 and 51. The claims read on a cell within a transgenic animal or a transgene therein given that the term "isolated" is not denoted in describing the host cell, nucleic acid, or expression vector.
With respect to the unisolated host cells and transgenes as “nucleic acids” or “expression vectors “of the instant claims discussed above, the state of the art at the time of filing was such that one of skill could not predict the phenotype of transgenics. The art of transgenic animals has for many years stated that the unpredictability lies, in part, with the site or sites of transgene integration into the target genome and that "the position effect" as well as unidentified control elements are recognized to cause aberrant expression of a transgene (Wall et Al., Theriogenology, Vol. 45, Pg. 57-68, 1996).
The elements of the particular construct used to make transgenic animals are also held to be critical, and they must be designed case by case without general rules to obtain good expression of a transgene; e.g., specific promoters, presence or absence of introns, etc. (Houdebine et Al., Journal of Biotechnology, Vol. 34, Pg. 269- 287, 1994). Furthermore, transgenic animals are regarded to have within their cells, cellular mechanisms that prevent expression of the transgene, such as methylation or deletion from the genome (Kappell et Al., Current Opinions in Biotechnology, Vol. 3, Pg. 548-553, 1992). Houdebine (Comparative Immunology, Microbiology, and Infectious Diseases, Vol. 32, Pg. 107-121, 2009) teaches progress has been made in the field of transgenic animals for production of foreign proteins (Abstract); however, constructing an efficient expression vector to produce a therapeutic protein is not a standard operation (Pg. 116, Paragraph, second). Therefore, undue experimentation is required to make and use a transgene and transgenic animal to produce the antibody and antibody fragments of the instant claims.
Examples in the literature aptly demonstrate that even closely related species carrying the same transgene construct can exhibit widely varying phenotypes. Mullins (1993, Hypertension, Vol. 22, No. 4, pp. 630-633) states that not all animals express a transgene sufficiently to provide a model for a disease as the integration of a transgene into different species of animal has been reported to give divergent phenotypes. For example, several animal models of human diseases have relied on transgenic rats when the development of mouse models was not feasible. Mullins (1990, Nature, Vol. 344, 541-544) produced outbred Sprague-Dawley x WKY rats with hypertension caused by expression of a mouse Ren-2 renin transgene. Hammer (1990, Cell, Vol. 63, 1099- 1112) describes spontaneous inflammatory disease in inbred Fischer and Lewis rats expressing human class I major histocompatibility allele HLA-B27 and human 02- microglobulin transgenes. Both investigations were preceded by the failure to develop human disease-like symptoms in transgenic mice expressing the same transgenes that successfully caused the desired symptoms in transgenic rats (Mullins, 1989, EMBO J., Vol. 8, pages 183-191). Thus, the use of nonmurine species for transgenesis will continue to reflect the suitability of a particular species for the specific questions being addressed, bearing in mind that a given construct may react very differently from one species to another.
The examiner notes here, in addition to these issues, even assuming arguendo a person having ordinary skill in the art could make a host organism with functional transgene that encodes the instantly recited SEQ ID NO: 1, there is no predictability that the host will survive its expression. The transgene depends on the host for function and harm to the host, including death, renders the transgene nonfunctional and thus not enabled.
The art is well-aware of side effects caused by expressing proteins, such as therapeutic antibodies. In a transgenic cell or animal that expresses the same, the antibody will exert any possible side effect it can. It is not administered but chronically present and so such side effects are chronic and potentially more serious than any from an administered antibody. Hansel (Nature Reviews Drug Discovery, Vol. 9, Pg. 325-337, 2010) teaches in their table 1 on page 328 numerous exemplary side effects from licensed monoclonal antibodies to include: increased bleeding risk, infection, heart failure, cancer, thyroid disorder, autoimmune reactions, and cytokine release syndrome (CRS) to name only a few. One or more such effects, or similar, may occur with the therapeutic antibody instantly recited when administered and indeed be exacerbated by chronic exposure due to internal expression. The instantly encoded antibody binds a mammalian protein and so may very well target related or unrelated proteins in the transgenic host, leading to such side effects. For all these reasons, previously raised and new, transgenes are not enabled.
At the time of filing, the phenotype of a transgene and transgenic cell contained within any animal was unpredictable. The claims as written, encompassing a transgene and cell in a transgenic animal, is not adequately described in the specification as to prevent excessive experimentation by the public to generate and use the invention. Applicants can obviate the instant rejection by amending the claim to recite the term "isolated" before the recitation, "host cell" and by amending the vector and polynucleotide claims to specify they are not in a transgenic animal. Applicant may consider using purified in such claims if description is appropriate for such a term and it is not redefined away from standard meaning. Method claims using these products should also carry the appropriate adjectives above.
In view of the lack of the predictability of the art to which the invention pertains as evidenced by the art above, the lack of guidance and direction provided by Applicant, and the absence of working examples, undue experimentation would be required to make and use transgenic animals possessing the claimed host cells, nucleic acid, or expression vector, with a reasonable expectation of success, absent a specific and detailed description in Applicant’s specification of how to effectively practice this and absent working examples providing evidence which is reasonably predictive that the claimed host cell, nucleic acid, or expression vector, commensurate in scope with the claimed invention. The same can be said for the transgenes and transgenic animals encompassed by the instant claims. Thus, the claims are rejected here.
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, 28 and 58 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, “wherein optional residues may be present or may be absent in whole or in part.” However, it is unclear which residues are optional, does this relate to the
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 28 recites the broad recitation “synthetic”, and the claim also recites “degreased” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 28 recite, “cryptic transmembrane domain”, however, the claim nor the specification explain or define what a renders a transmembrane domain cryptic. The claims nor the specification provide an explanation of what “the signature of a cryptic transmembrane domain” are. The state of the prior art also does not elaborate on what “the signature of a cryptic transmembrane domain” are. What renders a transmembrane domain cryptic and how does one of ordinary skill in the art know if it is a signature of a cryptic transmembrane domain.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 58 recites the broad recitation “transmembrane insertion potential”, and the claim also recites “(dG_ins)” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 58 recites the broad recitation “19-residue sliding window for transmembrane insertion potential”, and the claim also recites “(dG_INS)” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 58 recites the limitation "Windows of dG_ins" in line 5. The claims nor specification provide an explanation of what “Windows of dG_ins” are. The state of the prior art also does not elaborate on what “Windows of dG_ins” are. Therefore, it is unclear what the metes and bounds of this limitation are.
Claim 58 recites the limitation "the signature of a cryptic transmembrane domain" in lines 6-7. There is insufficient antecedent basis for this limitation in the claim.
Claim 58 recites in lines 6-7, “the signature of a cryptic transmembrane domain”. The claims nor the specification provide an explanation of what “the signature of a cryptic transmembrane domain” are. The state of the prior art also does not elaborate on what “the signature of a cryptic transmembrane domain” are. What renders a transmembrane domain cryptic and how does one of ordinary skill in the art know if it is a signature of a cryptic transmembrane domain.
Claim 58 recites the limitation "that domain" in line 9. There is insufficient antecedent basis for this limitation in the claim.
Claim 58 recites, “…are allowed to adopt different rotamers but not mutate to other.” It is unclear what “but not mutate to other” refers to. Is “other” referring to amino acids, domains or peptides?
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 58 recites the broad recitation “wherein allowed residues are all polar, excluding histidine”, and the claim also recites “such that the final allowable residues are amino acids D, E, K, R, Q, N, S, T, Y;” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Claims 26 and 51 are rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101). The claims are drawn to a host cell comprising the expression vector of claim 25 or a cell comprising the expression vector of claim 50. This host cell encompasses a human organism. If claims 26 and 51 are amended to recite, “An isolated host cell comprising the expression vector of claim 25.” And “An isolated cell comprising the expression vector of claim 50.”, respectively, this reject can be overcome.
Claims 1 and 2 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a naturally-occurring element of nature that is not patent-eligible pursuant to the Supreme Court decision in Association for Molecular Pathology V. Myriad Genetics, Inc., -- U.S. -- (June 13, 2013) (hereafter "Myriad").
Based upon an analysis with respect to the claims as a whole, claim(s) 1 and 2 do not recite something significantly different than a judicial exception. The rationale for this determination is explained below:
The claims do not fall within at least one of the four categories of patent eligible subject
matter because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more (these claims are interpreted in light of the most recent Guidelines (See 'https://www.uspto.gov/patent/laws-and-
regulations/examination-policy/subject-matter-eligibility).
These claims are analyzed for eligibility in accordance with their broadest reasonable
interpretation. In view of the Subject Matter Eligibility Test for Products and Processes the claims are directed to an ineligible product/process as further detailed below.
In this case, claim(s) 1 and 2 recite a polypeptide comprising an amino acid sequence with at least 75% identity to SEQ ID NO: 1 wherein the amino acid at position 37 is an arginine. Therefore, these claims are drawn to a composition of matter (Step 1) and recite natural phenomenon(s) (in this case, a naturally occurring polypeptide and nanoparticle comprising it) that are directed to a judicial exception (in this case, a natural phenomenon)(Step 2A).
GenBank Accession WP_038066850 presents the amino acid sequence of an aldolase of Thermotoga neapolitana, which possesses 90% identity with SEQ ID NO: 1 of the instant invention and possesses an arginine at position 37 relative to SEQ ID NO: 1 [see alignment below].
PNG
media_image1.png
401
715
media_image1.png
Greyscale
Therefore, the claimed polypeptide is interpreted as naturally occurring.
Thus the claimed product is not markedly different from its naturally occurring counterpart. To summarize, the claims read upon a composition of matter as recited in Step 1 and a natural phenomenon as recited in Step 2A and the claims do not recite the integration of the judicial exception into a practical application.
Further, in view of Step 2B and the "No" pathway, the claims do not recite additional
elements that amount to significantly more than the judicial exception. The claimed invention does not require a limitation that does not amount to significantly more than the judicial exception.
As pursuant to the Office's interpretation of the Myriad decision, a recitation of a naturally -occurring nucleic acid, protein and virus, or any natural product of nature that does not have a substantial or marked difference from the natural product is not patent eligible subject matter.
Therefore, claims 1 and 2 as written, read upon a polypeptide that was found to have occurred naturally in nature without being subject to the "hand-of-person" and resulting in a substantial or markedly different product from that found in nature.
Therefore, claim(s) 1 and 2 do not recite eligible subject matter under 35 U.S.C. 101 in view of the Subject Matter Eligibility Test for Products and Processes, and the claimed invention is directed to non-statutory subject matter.
This rejection is necessitated by expanded 35 USC § 101 USPTO training in view of the
USPTO's interpretation of Myriad. Applicant is directed towards the USPTO memos, which support the analysis of the claims; please review the latest materials regarding 35 USC § 101 rejections. Applicant is cautioned to amend the claims according to these suggestions utilizing limitations for which the application would have support.
Claim 58 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a naturally-occurring element of nature that is not patent-eligible pursuant to the Supreme Court decision in Association for Molecular Pathology v. Myriad Genetics, Inc., -- U.S.-- (June 13, 2013) (hereafter “Myriad”).
Based upon an analysis with respect to the claims as a whole, claim 58 do not recite something significantly different than a judicial exception. The rationale for this determination is explained below:
The claims do not fall within at least one of the four categories of patent eligible subject
matter because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more (these claims are interpreted in light of the most recent Guidelines (See 'https://www.uspto.gov/patent/laws-and-
regulations/examination-policy/subject-matter-eligibility).
The claims do not fall within at least one of the four categories of patent eligible subject
matter because the claimed invention is directed to a judicial exception (1.e., abstract idea)
without significantly more (these claims are interpreted in light of the most recent Guidelines (See www.uspgo.gov for further guidance). These claims are analyzed for eligibility in accordance with their broadest reasonable interpretation. In view of the Subject Matter Eligibility Test for Products and Processes and the Steps found at www.uspto.gov, the claims are directed to an ineligible process as further detailed below.
In this case, claim 58 recites a process of designing a secreted protein:
PNG
media_image2.png
488
884
media_image2.png
Greyscale
The steps of generating 3D structure of a protein of interest and designing one or more peptide sequences are interpreted as steps undertaken by a computer program or mental steps in which peptide sequences are optimized on paper, which results in the method not reciting an active step. Therefore, the claimed invention is drawn to a method or process of making (Step 1) and recite steps that are directed to judicial exceptions (in this case, abstract ideas)(Step 2A-Prong One). However, the steps are interpreted to be solely relying on a computer or mental steps which do not recite additional elements that integrate the abstract idea into a practical application. (Step 2A-Prong two)
Further, in view of Step 2B, the claims do not recite additional elements that amount to significantly more than the judicial exception. Presently, the method does not recite a limitation that would suggest anything more than using a computer program or mental steps in which peptide sequences are optimized on paper.
Consideration of the additional elements as a combination also adds no other meaningful
limitations to the exception not already present when the elements are considered separately. The claims do not invoke any of the considerations that courts have identified as providing significantly more than the exceptions. Even when viewed as a combination, the additional elements fail to transform the exceptions into a patent eligible application of that exception.
Thus, the claims as a whole do not amount to significantly more than the exception.
It is asserted that the claims are directed to judicial exceptions by reciting abstract ideas associated designing a peptide, without reciting more or additional elements that amount to significantly more than the judicial exception. Therefore, claim 58 does not recite eligible subject matter under 35 U.S.C. 101 in view of the Subject Matter Eligibility Test for Products and Processes, and the claimed invention is directed to non-statutory subject matter.
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 and 2 are rejected under 35 U.S.C. 102a1 as being anticipated by GenBank Accession WP_038066850 (published 11/11/2018).
The claimed invention is drawn to a polypeptide comprising an amino acid sequence with at least 75% identity to SEQ ID NO: 1 wherein the amino acid at position 37 is an arginine.
GenBank Accession WP_038066850 presents the amino acid sequence of a Thermotoga aldolase, which possesses 90% identity with SEQ ID NO: 1 of the instant invention and possesses an arginine at position 37 relative to SEQ ID NO: 1 [see alignment below].
PNG
media_image1.png
401
715
media_image1.png
Greyscale
Therefore, WP_038066850 anticipates the claimed invention.
Claim(s) 28, 48, 50 and 51 are rejected under 35 U.S.C. 102a1 as being anticipated by He and Zhu (US PGPub 2020/0009244).
The claimed invention is drawn to a synthetic nanoparticle, comprising a cryptic transmembrane domain, wherein one or more of the hydrophobic amino acids of the cryptic transmembrane domain have been substituted with a polar amino acid. The invention also requires a nucleic acid encoding the synthetic nanoparticle, an expression vector comprising this nucleic acid molecule and a cell comprising the expression vector.
In view of the 35 USC 112b rejections raised over claim 28 above, the claimed invention is interpreted to read on a synthetic nanoparticle that possesses a protein with a transmembrane domain, a nucleic acid that encodes this nanoparticle and an expression vector comprising this nucleic acid molecule and a cell comprising the expression vector.
He and Zhu teach the generation of self-assembling nanoparticles that comprises I3-01. [see paragraph 84] He and Zhu teach two amino acid sequences for I3-01 (SEQ ID NO:s 22 and 25). These sequences are 100% and 96.4% identical to SEQ ID NO: 1 of the instant application, respectively. He and Zhu also teach that the nanoparticle comprising I3-01 presents an immunogen, such as a HIV-1 trimer protein, on its surface. [see paragraph 84] The HIV-1 trimer protein can be made from HIV-1 gp140 (which comprises gp41) or a gp120 linked to a gp41, with these proteins possess a transmembrane domains since gp41 comprises this domain. [see paragraphs 53 and 62] He and Zhu additionally teach polynucleotides and expression vectors that encode the nanoparticles and HIV gp proteins and cells that possess the nucleic acid sequences. [see paragraphs 17 and 63]
Therefore, He and Zhu anticipate the instant invention.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-2, 14, 17, 23, 24-27 and 53 are rejected under 35 U.S.C. 103 as being unpatentable over He and Zhu (supra) and GenBank Accession WP_038066850 (published 11/11/2018).
The claimed invention is drawn to a polypeptide comprising an amino acid sequence with at least 75% identity to SEQ ID NO: 1 wherein the amino acid at position 37 is an arginine.
The claimed invention also requires a fusion protein comprising this polypeptide an a second functional polypeptide.
The claimed invention is also drawn to a nanoparticle that comprises a plurality of the polypeptide, or a composition comprising a plurality of the polypeptide, a nucleic acid sequence encoding the polypeptide, an expression vector that comprises the polypeptide, a host cell comprising the expression vector, a pharmaceutical composition comprising the composition of a plurality of the polypeptides, and a vaccine comprising the nanoparticle.
The Prior Art
He and Zhu teach the generation of self-assembling nanoparticles that comprises proteins of different origins and the use of these nanoparticles as vaccines. [see paragraph 9 and 11] For example, nanoparticles can be formed by I3-01 proteins, E2p proteins B. stearothermophilus and encapsulin from Thermotoga maritima. [see paragraphs 65 and 84] He and Zhu teach two amino acid sequences for I3-01 (SEQ ID NO:s 22 and 25). These sequences are 100% and 96.4% identical to SEQ ID NO: 1 of the instant application, respectively. He and Zhu also teach that the nanoparticle comprising I3-01 presents an immunogen, such as a HIV-1 trimer protein, on its surface. [see paragraph 84] The HIV-1 trimer protein can be made from HIV-1 gp140 (which comprises gp41) or a gp120 linked to a gp41, and gp41 comprises a transmembrane domain. [see paragraphs 53 and 62] The HIV-1 proteins teach the limitations of a fusion protein with a I3-01 fused to a second functional protein, since the HIV-1 proteins can function as a immunogen. He and Zhu additionally teach polynucleotides and expression vectors that encode the nanoparticles and HIV gp proteins and cells that possess the nucleic acid sequences. [see paragraphs 17 and 63]
However, He and Zhu do not teach that their I3-01 proteins possess an arginine at position 37.
GenBank Accession WP_038066850 presents the amino acid sequence of a variant of the I3-01 of He and Zhu, which possesses 90% identity with SEQ ID NO: 1 of the instant invention and possesses an arginine at position 37 relative to SEQ ID NO: 1 [see alignment below].
PNG
media_image1.png
401
715
media_image1.png
Greyscale
It would have been obvious to one of ordinary skill in the art to modify the compositions taught by He and Zhu in order to utilize another nanoparticle forming protein, such as a variant of I3-01. One would have been motivated to do so, given the suggestion by He and Zhu et al. that forming nanoparticles for the presenting an immunogen can involving more than one type of self-assembly protein, such as I3-01 proteins, E2p proteins B. stearothermophilus and encapsulin from Thermotoga maritima. There would have been a reasonable expectation of success, given the knowledge that proteins from Thermotoga with at least 75% identity and with a histidine at amino acid position 37 of were previously known, as taught by GenBank Accession WP_038066850. Thus the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/BENJAMIN P BLUMEL/Primary Examiner, Art Unit 1671