DETAILED ACTION
Disposition of Claims
Claims 20-38 are pending.
Examiner’s Note
All paragraph numbers (¶) throughout this office action, unless otherwise noted, are from the US PGPub of this application US20240366752A1, Published 11/07/2024.
Applicant is encouraged to utilize the new web-based Automated Interview Request (AIR) tool for submitting interview requests; more information can be found at https://www.uspto.gov/patent/laws-and-regulations/interview-practice.
Of note, there is not an attorney of record on file due to a lack of an official power of attorney of record. While a customer number has been provided on the ADS submitted 02/27/2024, this is not the equivalent of a power of attorney or an authorization to act in a representative capacity. In order to expedite prosecution in the instant application, it is suggested that a power of attorney be filed as per MPEP §402 or MPEP §1807, or an Authorization to Act in a Representative Capacity be filed as per MPEP §403 in order for the Office to freely and openly discuss the merits of the case with the applicant's representative(s). Please refer to https://www.uspto.gov/about-us/contact-us if you have questions regarding the proper filing of a power of attorney.
Optional Authorization to Initiate Electronic Communications
The Applicant’s representative may wish to consider supplying a written authorization in response to this Office action to correspond with the Examiner via electronic mail (e-mail). This authorization is optional on the part of the Applicant’s representative, but it should be noted that the Examiner may not initiate nor respond to communications via electronic mail unless and until Applicant’s representative authorizes such communications in writing within the official record of the patent application. A sample authorization is available at MPEP § 502.03, part II. If Applicant’s representative chooses to provide this authorization, please ensure to include a valid e-mail address along with said authorization.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/27/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Notably, the disclosure statement filed lists a Search Report. The listing of the references cited in a Search Report itself is not considered to be an information disclosure statement (IDS) complying with 37 CFR 1.98. 37 CFR 1.98(a)(2) requires a legible copy of: (1) each foreign patent; (2) each publication or that portion which caused it to be listed; (3) for each cited pending U.S. application, the application specification including claims, and any drawing of the application, or that portion of the application which caused it to be listed including any claims directed to that portion, unless the cited pending U.S. application is stored in the Image File Wrapper (IFW) system; and (4) all other information, or that portion which caused it to be listed. In addition, each IDS must include a list of all patents, publications, applications, or other information submitted for consideration by the Office (see 37 CFR 1.98(a)(1) and (b)), and MPEP § 609.04(a), subsection I. states, "the list ... must be submitted on a separate paper." Therefore, the references cited in the Search Report have not been considered. Applicant is advised that the date of submission of any item of information or any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the IDS, including all "statement" requirements of 37 CFR 1.97(e). See MPEP § 609.05(a).
Note: If copies of the individual references cited on the Search Report are also cited separately on the IDS (and these references have not been lined-through) they have been considered.
Claim Objections
Claim 32 is objected to because of the following informalities: the definition of the abbreviation “SARS-CoV-2” is not provided. For clarity, it is requested that the first recitation of an abbreviation within a claim set be preceded by its full-length name (i.e. … severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)...).
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b); Second Paragraph
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.
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.
Claim 38 is rejected under 35 U.S.C. 101 because the claimed invention is not supported by either a specific and substantial asserted utility or a well-established utility.
Claim 38 is drawn to the “use of a recombinant adenovirus, obtained by transfecting an adenovirus with the recombinant expression vector according to claim 20 and culturing the transfected adenovirus, as an active ingredient, for preventing or treating a coronavirus disease (COVID-19).” Attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. For example, a claim which read: “[a] process for using monoclonal antibodies of claim 4 to isolate and purify human fibroblast interferon” was held to be indefinite because it merely recites a use without any active, positive steps delimiting how this use is actually practiced. Ex parte Erlich, 3 USPQ2d 1011 (Bd. Pat. App. & Inter. 1986). See MPEP §2173.05(q). In the instant claim, the recombinant adenovirus is claimed as being used “for preventing or treating a coronavirus disease” without reciting any active method steps as to how one would actually perform the preventing or treating of said disease.
Claim 38 is also rejected under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph. Specifically, because the claimed invention is not supported by either a specific and substantial asserted utility or a well-established utility for the reasons set forth above, one skilled in the art clearly would not know how to use the claimed invention.
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.
Claims 27-28 are rejected under 35 U.S.C. 101 because Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Claims 27-28 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). Claim 27 is drawn to a recombinant transformant transformed with the recombinant expression vector according to claim 20, and claim 28 depends upon claim 27 and notes the transformant may be “a cell” or “an animal”. As the claim and specification do not qualify the “animal” as a “non-human animal”, it does not exclude a human as reasonably being encompassed by the claim. Likewise, as the “cell” is not noted as being an “isolated” cell, this also reasonably reads upon a human organism.
With respect to claim 27, one suggested amendment is to provide a negative limitation to claim 27 so that it clearly does not read on a human organism (e.g. “An isolated recombinant transformant, wherein the recombinant transformant is not a human organism, transformed with the recombinant expression vector according to claim 20.”)
With respect to claim 28, it is suggested the claim be amended to read upon “isolated cells” and “non-human animals” (e.g. “The isolated recombinant transformant according to claim 27, wherein the transformant is selected from the group consisting of a microorganism, an isolated cell, a non-human animal, a plant, and a virus.”)
This suggested language is offered as a guide, as applicant is free to amend the claims however necessary in order to overcome the rejection.
Claim Rejections - 35 USC § 112(b); Second Paragraph
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.
Claim 20 and dependent claims 21-38 thereof 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 20 is rejected for claiming the limitation of an amino acid position within a protein sequence without providing an appropriate frame of reference for said sequence. Said frame of reference can be provided by referencing a sequence disclosed within the application (i.e. a sequence with a SEQ ID NO: identifier). Further, as the claim is generically drawn to any coronavirus spike protein, which reasonably reads on the spike protein of various viruses, such as SARS CoV, SARS CoV-2, MERS CoV, HuCoV 229E, HuCoV OC43, or HuCoV NL63, it is unclear if the numbering is applicable to all CoV spike proteins, especially since further dependent claims note that the mutation is a D to G substitution mutation and it is not clear that all CoV spike proteins comprise this amino acid at this position.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant claim 20 is rejected on the grounds of being indefinite. Claims 21-38 are also rejected since they depend from claim 20, but do not remedy these deficiencies of claim 20.
Claims 31, 35, and 38 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.
It is unclear if the recited element within parentheses (See e.g. "(COVID-19)") is a required element of the claim. It is suggested that the Applicant amend the claim to either remove the parentheses and have it as a “wherein” statement that further limits the “coronavirus disease” (e.g. “…for preventing or treating a coronavirus disease, wherein said coronavirus disease is COVID-19.”) or amend the claims to recite the items within the parentheses as additional dependent claims which further limit the independent, parent claim.
For at least these reasons, claims 31 and 38 are rejected on the grounds of being indefinite.
Claim 31 and dependent claims 32-34 thereof 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 31 recites the limitation "the recombinant expression vector according to claim 27" in line 2. The antecedent basis for this limitation in the claim is not directly clear due to the wording of the claim, as claim 27 is drawn to “a recombinant transformant” wherein said transformant comprises the vector of claim 20, but claim 27 also does recite “the recombinant expression vector according to claim 20” in lines 1-2 of the claim. As claim 31 uses the indefinite article “a” before “transformant”, it is unclear as to which transformant is being referenced. It is unclear if the claim is meant to be drawn to “A vaccine composition…comprising the transformant according to claim 27” or if the claim is meant to be drawn to “A vaccine composition… comprising a transformant transformed with the recombinant expression vector according to claim 20.” The former option clarifies the antecedence of the transformant, while the latter allows for the use of any transformant and clarifies the antecedence of the vector.
Further dependent claims also have additional clarity issues due to this antecedent basis issue. For instance, claim 32 depends upon the vaccine composition according to claim 31, wherein the transformant expresses a SARS CoV-2 recombinant protein. However, it is unclear if this “SARS CoV-2 recombinant protein” is meant to further limit the “coronavirus surface spike protein (S protein) comprising a mutation at amino acid position 614 of the spike protein” of claim 20, or if said SARS CoV-2 recombinant protein is an additional recombinant protein expressed by the vector. If the transformant is an animal or plant, it is unclear how it can be administered intramuscularly or through any of the other routes of dependent claim 33, or how an animal can prevent coronavirus disease in another animal as in claim 34. As set forth supra, it is unclear what is meant by “COVID-19” in parentheses in claim 31, and then to have claim 34 recite various specific coronaviruses (CoV) that do not cause COVID-19 disease makes the metes and bounds of the vaccine composition unclear.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant claim 31 is rejected on the grounds of being indefinite. Claims 32-34 are also rejected since they depend from claim 31, but do not remedy these deficiencies of claim 31.
Claim 33 is 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.
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 33 recites the broad recitation “administered intranasally”, and the claim also recites “inhaled intranasally” 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.
Claims 35-38 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.
Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The term “transfecting” in claims 35-38 is used by the claim to mean “engineering” or “recombining”, while the accepted meaning is “the process of deliberately introducing foreign nucleic acids (such as DNA, RNA, or proteins) into eukaryotic cells.” The term is indefinite because the specification does not clearly redefine the term. It is unclear what is meant by “transfecting an adenovirus with the recombinant expression vector” and “culturing the adenovirus”. Transfection and culturing are typically terms used in reference to tissue culture/cell culture, and the introduction of foreign genetic material into a viral vector, such as adenovirus, is typically referred to as “viral recombination”, “recombineering”, or “viral genome engineering”.
For at least these reasons, the metes and bounds of claims 35-38 are unclear.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
Claim 20 is drawn to a recombinant isolated expression vector comprising:
a gene sequence encoding a coronavirus (CoV) surface spike protein (S protein) comprising a mutation at amino acid position 614 of the spike protein;
an adjuvant gene sequence; and
a gene sequence encoding a P2A peptide.
Further limitations on the recombinant expression vector according to claim 20 are wherein the gene sequence encoding the coronavirus surface spike protein (S protein) comprising the mutation at amino acid position 614 of the spike protein is set forth in SEQ ID NO: 1 (claim 21); wherein the mutation is an aspartic acid (D)-to-glycine (G) substitution (claim 22); wherein the adjuvant gene sequence is a chemokine (C-X-C motif) ligand 9 (CXCL9) gene, or an interleukin 7 (IL-7) gene (claim 23), wherein the chemokine (C-X-C motif) ligand 9 gene is set forth in SEQ ID NO: 2 (claim 24), wherein the interleukin 7 gene is set forth in SEQ ID NO: 3 (claim 25); and wherein the gene encoding a P2A peptide is set forth in SEQ ID NO: 5 (claim 26).
Claim 27 is drawn to an isolated recombinant transformant, wherein the recombinant transformant is not a human organism or transgenic animal, transformed with the recombinant expression vector according to claim 20.
Further limitations on the isolated recombinant transformant according to claim 27 are wherein the transformant is selected from the group consisting of a microorganism, an isolated cell, a non-human animal, a plant, and a virus (claim 28), wherein the virus is an adenovirus (claim 29), and wherein the adenovirus is adenovirus type 5 (Ad5)(claim 30).
Claim 31 is drawn to a vaccine composition for preventing a disease caused by a coronavirus (CoV) infection, wherein the composition comprises the transformant according to claim 27.
Further limitations on the vaccine composition according to claim 31 are wherein the transformant expresses a SARS-CoV-2 recombinant protein (claim 32); wherein the vaccine composition is administered intramuscularly, administered intranasally, or inhaled intranasally (claim 33); and wherein the coronavirus is at least one selected from the group consisting of human coronavirus 229E (HCoV-229E), human coronavirus OC43 (HCoV-OC43), human coronavirus HKU1 (HCoV-HKU1), human coronavirus NL63 (HCoV-NL63), severe acute respiratory syndrome coronavirus (SARS-CoV), severe acute respiratory syndrome virus-2 (SARS-CoV-2), Middle East respiratory syndrome coronavirus (MERS-CoV), porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine hemagglutinating encephalomyelitis virus (PHEV), bovine coronavirus (BCoV), equine coronavirus (EqCoV), murine coronavirus (MuCoV), canine coronavirus (CCoV), feline coronavirus (FCoV), Miniopterus bat coronavirus-1, Miniopterus bat coronavirus HKU8, Rhinolophus bat coronavirus HKU2, Scotophilus bat coronavirus 512, Tylonycteris bat coronavirus HKU4, Pipistrellus bat coronavirus HKU5, Rousettus bat coronavirus HKU9, avian coronavirus, Beluga whale coronavirus SW1, Bulbul coronavirus HKU11, Thrush coronavirus HKU12, and Munia coronavirus HKU13 (claim 34).
Claim 35 is drawn to a coronavirus disease prime-boost vaccine composition comprising, as an active ingredient, a recombinant adenovirus (rAdV) obtained by transfecting an adenovirus (AdV) with the recombinant expression vector according to claim 20 and culturing the transfected adenovirus.
Claim 36 is drawn to a pharmaceutical composition for preventing or treating a coronavirus disease (COVID-19) comprising, as an active ingredient, a recombinant adenovirus obtained by transfecting an adenovirus with the recombinant expression vector according to claim 20 and culturing the transfected adenovirus.
Claim 37 is drawn to a method for preventing or treating coronavirus disease (COVID-19) comprising a step of administering a recombinant adenovirus obtained by transfecting an adenovirus with the recombinant expression vector according to claim 20 and culturing the transfected adenovirus.
Claim 38 is drawn to the use of a recombinant adenovirus, obtained by transfecting an adenovirus with the recombinant expression vector according to claim 20 and culturing the transfected adenovirus, as an active ingredient, for preventing or treating a coronavirus disease (COVID-19).
Claim Rejections - 35 USC § 112(a); First Paragraph
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 20-28 and 31-34 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 isolated recombinant expression vectors and recombinant adenovirus (Ad5) transformant systems, namely pShuttle-CMV/pAdEasy-1 constructs and Adeno-X 293 constructs, does not reasonably provide enablement for the broader genus of recombinant transformants or non-isolated expression vectors as presently claimed. The specification does not 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.
Claim 20 is directed broadly to a “recombinant expression vector” and claim 27 is directed broadly to “recombinant transformant” without either having limitation as to form, environment, or method of use of said expression vector or any system that is transformed with the recombinant expression vector (nucleic acid) of claim 20. As such, the claims encompass nucleic acid vectors and systems comprising said vectors in a wide range of contexts, including incorporation into other vectors, plasmids, artificial chromosomes (e.g. bacterial or yeast artificial chromosomes (BACs or YACs)), cosmids, prokaryotic and eukaryotic cells, and organismal systems (e.g. Bacteria and Archaea, Eukaryotes (including vertebrate and invertebrate animals, plants, and fungi), and viruses). The specification supports this interpreted breadth at ¶[0028].
The specification does not provide guidance sufficient to enable the use of the claimed nucleic acid across this full scope of recombinant transformants, including in complex biological systems where expression, stability, and functionality may vary depending on the host environment and delivery method.
Accordingly, undue experimentation would be required to determine how to make and use the claimed recombinant transformants with the claimed nucleic acid vectors across the full scope of the claims. It is suggested that the claims be amended to read upon “an isolated recombinant expression vector” [emphasis added] in order assist in overcoming this rejection. With respect to the recombinant transformants of claim 27 and dependent claims thereof, it is suggested, in light of the additional rejections supra and this scope of enablement rejection, that the transformants be specifically narrowed to only those for which there is enabling support in the specification, such as the Ad5 vector transformants.
Claims 20-38 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for recombinant adenovirus 5 (Ad5) vector constructs comprising the disclosed SARS CoV-2 spike (S) nucleic acid/protein sequences, human CXCL9 and IL-7 sequences, and P2A sequences, does not reasonably provide enablement for the broader scope of the claimed recombinant expression vectors or transformants, the claimed vaccine/pharmaceutical compositions, and the methods of use of said components, especially as they are drawn to any coronavirus spike protein with the claimed mutation. The specification does not 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 legal considerations that govern enablement determinations pertaining to undue experimentation have been clearly set forth. Enzo Biochem, Inc., 52 U.S.P.Q.2d 1129 (C.A.F.C. 1999). In re Wands, 8 U.S.P.Q.2d 1400 (C.A.F.C. 1988). See also MPEP § 2164.01(a) and § 2164.04. Ex parte Forman 230 U.S.P.Q. 546 (PTO Bd. Pat. App. Int., 1986). The courts concluded that several factual inquiries should be considered when making such assessments including: the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples, the nature of the invention, the state of the prior art, the relative skill of those in that art, the predictability or unpredictability of the art and the breadth of the claims. In re Rainer, 52 C.C.P.A. 1593, 347 F.2d 574, 146 U.S.P.Q. 218 (1965). The disclosure fails to provide adequate guidance pertaining to a number of these considerations as follows:
Nature of the invention/Breadth of the claims. The claimed invention is drawn to recombinant expression vectors comprising any coronavirus (CoV) spike protein gene sequence having a mutation at amino acid 614, an adjuvant gene sequence, and a gene sequence encoding a P2A peptide. The claims further encompass transformants comprising the vectors and compositions, methods of using said compositions to therapeutically treat or inhibit CoV infection or disease in a subject, and is drawn to recombinant adenoviruses (AdV) comprising said vectors. Note the issues with certain limitations and the breadth of the claims addressed in the 35 USC 112b rejections supra.
Note that “coronavirus” is drawn to any member of the family Coronaviridae, of which there are over 50 officially recognized species, categorized into 2 subfamilies, 6 genera, and 28 subgenera. The main subfamily Orthocoronavirinae comprises the viruses colloquially referred to as “coronaviruses” and contains four genera: alpha-, beta-, gamma-, and delta-coronavirus. Of the many members of this family, only 7 are known to infect humans: Alpha coronaviruses: 229E and NL63; and Beta coronaviruses: OC43, HKU1, SARS-CoV, MERS-CoV, and SARS-CoV-2.
“CXCL9” and “IL-7” can be any of these chemokines found in any species and are not limited to only those sequences which are found in humans.
The specification describes recombinant Ad5 vectored vaccine candidates comprising a SARS CoV-2 S protein with a D614G mutation, with and without a stabilizing 2P mutation (Figs. 1-3; Example 1 starting at ¶[0104]). The disclosed constructs include human CXCL9 or IL-7 where an adjuvant is included, wherein a P2A sequence separates the adjuvant sequence from the S protein sequence (¶[0105]). However, claim 20 is not only limited to the disclosed SARS CoV-2 S protein sequences, the D614G substitution, human CXCL9, human IL-7, or the disclosed P2A sequence. Further dependent claims expressly extend the vaccine composition to other non-SARS CoV-2 CoV.
State of the prior art/Predictability of the art. Applicant’s background art states that there was an urgent need for vaccine candidates for the emerging SARS CoV-2 pandemic, and such vaccine platforms included inactivated and attenuated viruses, subunit vaccines, RNA vaccines, DNA vaccines, and viral vector vaccines. Despite advances in vaccine platform technology, research on the most effective delivery routes for vaccines is limited. Since SARS-CoV-2 infects via the respiratory tract, intranasal vaccination should be effective. However, poor understanding of mucosal vaccines has limited their development to the stage of human clinical trials (¶[0005]).
To eradicate SARS-CoV-2 and prevent further infections, many vaccine candidates have been developed. The delivery of these vaccines is limited to intramuscular vaccination, in contrast to the diversity in the platform technology. Although intramuscular vaccination is safe and effective, mucosal vaccination could improve the local immune responses that block the spread of pathogens. However, due to a lack of understanding of mucosal immunity combined with the urgent need for a COVID-19 vaccine, only intramuscular vaccinations have become possible (¶[0006]).
Further art supports Applicant’s statements as to the state of the vaccine art, especially as it relates to CoV vaccines. Hassan et. al. (Hassan AO, et. al. Cell. 2020 Oct 1;183(1):169-184.e13. Epub 2020 Aug 19.) evaluated a chimpanzee adenovirus (ChAdV) vectored vaccine encoding a prefusion-stabilized SARS CoV-2 S protein. Hassan reported that intramuscular administration induced systemic humoral and cell-mediated immune responses and provided protection against lung infection, inflammation, and further pathology, but did not confer sterilizing immunity. In contrast, intranasal administration induced neutralizing antibodies and systemic and mucosal IgA and T-cell responses and almost entirely prevented infection in both the upper and lower respiratory tracts. These intranasal ChAd-vectored vaccine (also known as BBV154 or iNCOVACC) has successfully completed phase 3 clinical trials. It received emergency use authorization and was launched as a needle-free primary series and booster in India (Singh C, et. al. NPJ Vaccines. 2023 Aug 18;8(1):125.)
King et. al. (King RG, et. al. Vaccines (Basel). 2021 Aug 9;9(8):881.) evaluated an intranasally administered replication-deficient Ad5 vaccine encoding the SARS CoV-2 receptor binding domain (RBD). King reported induction of respiratory mucosal IgA, serum neutralizing antibodies, and a broad range of T cell responses in mice. King further stated future preclinical studies would investigate protection against non-vaccine matched viral challenge. However, it is well noted in the art that pre-existing Ad5 neutralizing antibodies can have a significant effect on the immunogenicity of resulting SARS CoV-2-Ad5 vaccine platforms (Liu W, et. al. Vaccines (Basel). 2025 Mar 20;13(3):333.).
These references show that the immune response and protective effect of an AdV-vectored vaccine depended on the selected antigen, the route of administration, and the selected AdV vector for delivery, and required extensive empirical evaluation to establish the effectiveness of such a vector for vaccine delivery. The disclosed results from Applicant using only the identified SARS CoV-2 S protein Ad5 constructs and CXCL9/IL-7 adjuvants would not have reasonably established that additional vectors comprising fragments of the S protein, other CoV S proteins or fragments thereof (especially with the claimed 614 mutation), other adjuvant genes, or other construct components would provide an effective vaccine across the full claimed scope.
Level of Skill in the Art. One of skill in the art at the time of filing would have been familiar with methods for preparing recombinant vectors, such as recombinant AdV-based vectors, and the methods for evaluating candidate vaccines in vitro and in vivo. The specification describes vector construction and purification (¶[0104-0106]), antibody analysis after inoculation into mice (Example 2 starting at ¶[0107]), optimization of vaccination route (Example 3 starting at ¶[0108]), and optimization of antigen and adjuvant selection (Examples 4-5 starting at ¶[0109]). However, the ability to prepare and test candidate constructs does not establish that one skilled in the art would have known which additional constructs would satisfy the breadth of the claimed scope without further empirical and undue experimentation.
Working examples. The specification describes the construction of Ad5-based vectors (Ad5(S D614G 2P-CXCL9), Ad5(SD 614G 2P), Ad5(SD614G-CXCL9), Ad5(SD614G-IL-7)) in Example 1 starting at ¶[0104], wherein the 2P mutations were designed to stabilize the S protein in the prefusion formation. Examples 2-6 optimize the system, antigens, and adjuvants used while evaluating the immunogenicity of the candidate Ad5-vectored vaccines in mice (¶[0107-0115]) while Example 7 evaluates protection against SARS CoV-2 challenge in mice humanized with the human ACE2 receptor, which makes said mice susceptible to wild-type SARS CoV-2 infection (¶[0116-0117]). The specification does not provide any working examples with any other CoV S proteins. The specification does not test any other AdV vector platforms, such as chimeric AdV or AdV which infect other non-human species. The pAdEasy-1 system used by the Applicant is based on Human Adenovirus Serotype 5 (Ad5) and is attenuated, specifically through engineered replication-deficiency, wherein said Ad5 comprises a 1-3,533 deletion that encompasses the E1 genes and a 28,130-30,820 deletion that encompasses the E3 region, and because of these attenuations, must be propagated in specific host cell lines that provide the missing E1 gene in trans. The specification does not teach any other 614 mutations in any other CoV S proteins. The specification does not use any other adjuvants, any non-human forms of CXCL9 or IL-7, or any other P2A sequences, nor does the specification provide any of these three required items from instant claim 20 in any other particular orientation, location, or order within the vector.
Guidance in the specification. The specification provides guidance towards preparing the disclosed SARS CoV-2 S protein Ad5 vaccine candidates expressing either human CXCL9 or IL-7 (¶[0104-0106]). The specification also provides results in mice and mice expressing human ACE2 regarding immunization and SARS CoV-2 challenge studies (¶[0108-0117]). However, the specification does not provide sufficient guidance for selecting and using additional CoV S proteins having any mutation (e.g. insertion, deletion, or substitution) at amino acid position 614. The specification fails to provide guidance as to what other adjuvant genes may be used, or which additional transformants would provide an effective vaccine. The specification also fails to provide guidance for extending the disclosed SARS CoV-2 results to the additional human and animal CoV recited in dependent claim 34.
Amount of experimentation necessary. Additional research is required in order to determine how to make and use the full scope of the instant claims. To practice the full scope of the claims, one skilled in the art would need to select additional CoV spike sequences, generate a variety of mutations at amino acid 614, select additional adjuvant sequences and test said sequences in the vector, prepare additional recombinant vectors, produce and isolate transformants, confirm the correct insertion and expression of the vector in the transformant, and then test the delivery route, safety, and efficacy of using said transformant as a vaccine against the homologous or heterologous CoV from which the S protein was obtained and used for said vector.
In light of the Supreme Court decision in Amgen Inc. et al. v. Sanofi et al., 143 S. Ct. 1243 (2023) (hereafter Amgen), updated guidelines were provided regarding the assessment of enablement (Federal Register, pp. 1563-1566; Pub. Jan. 10, 2024.) While the specification need not describe how to make and use every individual embodiment within the claimed scope, the specification must enable one skilled in the art to make and use the full scope of the claimed invention without undue experimentation. In the instantly claimed invention, the specification describes only a limited group of recombinant SARS CoV-2 S-Ad5 vector vaccine candidates, and fails to provide sufficient guidance or show data from additionally tested embodiments to prevent a skilled artisan from having to undergo undue experimentation to make and/or use the breadth of the scope of the instant claims.
For at least the reasons discussed above, it would require undue experimentation for one skilled in the art to make the claimed products, vectors, and compositions and use them in the claimed methods.
Claims 20-38 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The 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 20-38 are rejected as lacking adequate descriptive support for any recombinant expression vector comprising any gene sequence encoding any CoV S protein with any amino acid mutation at position 614, any adjuvant gene sequence, and any P2A sequence in any order or configuration in said vector, and for any method of using said vector to generate an immune response in any subject that would provide therapeutic or prophylactic immune responses against any CoV.
In support of the claimed genera noted supra, the application discloses Examples 1-7, detailed supra in the scope of enablement rejection, that discuss the generation of specific SARS CoV-2 D614G S protein mutants in attenuated Ad5 vectors, wherein said vectors either express human IL-7 or human CXCL9, and the testing of said vectors in different mouse models to determine the immunogenicity of said vectors and the ability of said immunizations to directly protect against wild-type SARS CoV-2 challenge. However, claim 20 is not limited to these disclosed constructs, and instead encompasses any gene sequence using any codon-optimization to encode any CoV spike protein with any insertion, deletion, or substitution mutation at position 614 of said spike protein. Claim 20 does not limit the mutation to only D614G, nor does claim 20 limit the adjuvant gene sequence or P2A sequences, where said sequences are found in the Ad5 vector, or the arrangement of said sequences. Claim 20 does not limit the specific vector system, and even though dependent claims narrow the vector/transformant to AdV vectors, namely Ad5 vectors, no other AdV or Ad5 vector systems have been studied or described; likewise no other vector systems aside from Ad5 were tested or described, and the specification fails to describe relevant structural characteristics sufficient to show possession of the broadly claimed genus of expression vectors. Claim 20 also does not limit the adjuvant; while dependent claims narrow the adjuvant to CXCL9 or IL-7 and specific sequences of each, the sequences are only from human versions of these proteins, and no other version of these cytokines were used or tested, nor is there sufficient description to provide guidance as to what type of adjuvants to use or avoid (e.g. use of specific types of adjuvants to aid in a Th1 vs Th2-skewed response, etc.) Further, while dependent claims may narrow one genera to specific embodiments which were tested, the breadth of the other required genera still remains broad, and it is not clear that said limitations or permutations were tested for by applicant. Likewise, only a limited number of vaccines were tested against viral challenge, and it is unclear if applicant was in possession of the scope of the broadly claimed methods which could treat or prevent disease from any CoV. Thus, the application fails to provide a sufficient number of examples of species within the broadly claimed genera.
Thus, in view of the above, there would have been significant uncertainty as to which expression vector constructs could be generated and would be able to confer the claimed functional immunogenicity against the breadth of viruses. In view of this uncertainty and the lack of sufficient examples of the broadly claimed genera, the claims are rejected for lack of adequate written description support.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 20, 22-25, and 27-38 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Benmohamed (US20230226173A1, Pub. 07/20/2023, Priority 04/14/2020; hereafter “Benmohamed”) as evidenced by Strausberg et. al. (Strausberg RL, et. al. Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16899-903. Epub 2002 Dec 11. and associated GenBank Dep. Strausberg RL, et. al. Homo sapiens interleukin 7, mRNA (cDNA clone MGC:51943 IMAGE:5748841), complete cds. GenBank: BC047698.1, Dep. 03/20/2003.; hereafter “Strausberg.”)
The Prior Art
Benmohamed teaches a recombinant antigen delivery system encoding coronavirus (CoV) whole spike (S) proteins or epitopes thereof, wherein said antigen delivery system is a vaccine composition (entire document; see abstract; ¶[0023-0024]). Benmohamed teaches SARS CoV-2 variant antigens and states that the S protein may comprise a D614G mutation (¶[0034-0036][0045][0117][0277]). Benmohamed further recites SARS CoV-2 circulating strains and variants (Fig. 2), wherein the majority of the strains, such as those listed in ¶[0248] like B.1.177 (Spain strain EU1), inherently comprise the D614G mutation. Benmohamed teaches that the composition may comprise CXCL9 and IL-7 (¶[0289][0293][0306]; Table 13), and teaches that these may be integrated into the same delivery system as the vaccine compositions (¶[0293]), and that a linker, such as P2A, may be placed in between the antigen and the IL-7 and/or CXCL9 (¶[0306]). SEQ ID NO: 158 of Benmohamed is 100% identical to instant SEQ ID NO: 2 (see us-18-686-928-2.rnpbm ABSS result file; instant claim 24) and IL-7 in its natural form inherently has the sequence that is 100% identical to SEQ ID NO:3 (see us-18-686-928-3.rge ABSS result file; instant claim 25). Benmohamed teaches that an antigen delivery system may be adenovirus Ad5 viral vectors (¶[0076][0105-0108][0298]; instant claims 27-30). Benmohamed therefore teaches an isolated recombinant expression vector comprising a SARS CoV-2 S protein comprising a D614G mutation, an adjuvant gene sequence such as CXCL9 or IL-7, and a P2A peptide, and vaccine compositions thereof, wherein the expression vector is within an Ad5 vector, and anticipates the limitations of instant claims 20, 22-24, and 27-32.
Benmohamed teaches that the vaccine composition may be administered intravenously, intranasally, sublingually (¶[0326], or intramuscularly (¶[0197]; instant claim 33). Benmohamed teaches the vaccine may be used to treat or protect against coronavirus infection or disease in a subject, such as infection or disease caused by SARS CoV-1 or SARS CoV-2 (¶[0084][0096][0101][0194]; instant claims 34, 36). Benmohamed teaches engineering of the SARS CoV-2 antigens, linkers, tags, adjuvants, and chemokines into the different delivery systems using standard molecular biology techniques known in the art (¶[0184][0315]). Benmohamed teaches the vaccine may be used in a prime/boost vaccination regimen (¶[0175][0328][0330-0331]; Fig. 25; instant claims 35, 37-38).
For at least these reasons, Benmohamed teaches the limitations of instant claims 20, 22-25, and 27-38, and anticipates the invention encompassed by said claims.
Claims 20, 22, and 27-38 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Tucker et. al. (WO2021248017A2, Pub. 12/09/2021, Priority 06/05/2020; hereafter “Tucker”).
(NB: Tucker would additionally qualify under 35 U.S.C. 102(a)(1) based on its 12/09/2021 publication date if applicant fails to establish that the rejected claims are entitled to the 08/27/2021 priority date.)
The Prior Art
Tucker teaches chimeric adenoviral vectors comprising a nucleic acid encoding a coronavirus disease 2019 (COVID-19) protein and an adjuvant and methods for using the vectors to elicit an immune response to the SARS-CoV-2 protein in order to treat COVID-19 (entire document; see abstract.) Tucker teaches SEQ ID NO: 21, which aligns with 99% identity to instant SEQ ID NO: 1, and comprises the D614G mutation (see alignment below; SEQ ID NO: 1 is “Db” while SEQ ID NO:21 is “Qy”.) Tucker teaches that IL-7 may be used as an adjuvant (¶[0124]), and that P2A elements can exist within the vector encoding the antigens to separate multiprotein transcripts (¶[0090]). Tucker teaches that the chimeric adenoviral vectors can also include a nucleic acid encoding a toll-like receptor (TLR) agonist (e.g. a TLR3 agonist) which can serve as an effective adjuvant when administered in conjunction with viral vectors (¶[0071]). Tucker therefore teaches a recombinant adenovirus expression vector which comprises a gene encoding a SARS CoV-2 S protein with a D614G mutation, a P2A peptide, and an adjuvant gene sequence, thus anticipating the limitations of instant claims 20, 22, and 27-29.
Tucker teaches the adenovirus may be an adenovirus 5 (Ad5) vector (¶[0097-0098] ; instant claim 30). Tucker teaches immunogenic compositions comprising the chimeric adenoviral expression vector and a pharmaceutically acceptable carrier (¶[0024]; reference claim 29), wherein said compositions may be vaccines for treating COVID-19 (¶[0035-0043][0047]; instant claims 31-32, 34, 36). Tucker teaches the immunogenic compositions may be delivered intranasally or intramuscularly (¶[0101]; instant claim 33). Tucker teaches the compositions may be administered and then followed by booster vaccinations (¶[0130]; instant claim 35). Tucker teaches molecular biology techniques in order to generate the recombinant adenovirus vectors (Example 1 starting at ¶[0135]). Tucker teaches methods for eliciting an immune response towards a SARS-CoV-2 protein in a subject, comprising administering to the subject an immunogenically effective amount of the chimeric adenoviral expression vector or an immunogenic composition comprising said vector to a mammalian subject (reference claims 30, 57; ¶0059-0061][0127-0134]; instant claims 37-38).
For at least these reasons, Tucker teaches the limitations of instant claims 20, 22, and 27-38, and anticipates the invention encompassed by said claims.
Query Match 99.0%; Score 6642.5; DB 1; Length 1273;
Best Local Similarity 99.3%;
Matches 1264; Conservative 1; Mismatches 5; Indels 3; Gaps 2;
Qy 1 MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFS 60
Qy 61 NVTWFHAI--SGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIV 118
|||||||| ||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIV 120
Qy 119 NNATNVVIKVCEFQFCNDPFLGV-YHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLE 177
||||||||||||||||||||||| ||||||||||||||||||||||||||||||||||||
Db 121 NNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLE 180
Qy 178 GKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQT 237
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQT 240
Qy 238 LLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETK 297
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 LLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETK 300
Qy 298 CTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISN 357
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 CTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISN 360
Qy 358 CVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIAD 417
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 CVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIAD 420
Qy 418 YNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPC 477
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 YNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPC 480
Qy 478 NGVEGFNCYFPLQSYGFQPTYGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVN 537
|||||||||||||||||||| |||||||||||||||||||||||||||||||||||||||
Db 481 NGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVN 540
Qy 538 FNFNGLTGTGVLTESNKKFLPFQQFGRDIDDTTDAVRDPQTLEILDITPCSFGGVSVITP 597
||||||||||||||||||||||||||||| ||||||||||||||||||||||||||||||
Db 541 FNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITP 600
Qy 598 GTNTSNQVAVLYQGVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSY 657
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 GTNTSNQVAVLYQGVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSY 660
Qy 658 ECDIPIGAGICASYQTQTNSHRRARSVASQSIIAYTMSLGAENSVAYSNNSIAIPINFTI 717
|||||||||||||||||||| |||||||||||||||||||||||||||||||||| ||||
Db 661 ECDIPIGAGICASYQTQTNSPRRARSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTI 720
Qy 718 SVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQE 777
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 SVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQE 780
Qy 778 VFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDC 837
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 VFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDC 840
Qy 838 LGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAM 897
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 LGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAM 900
Qy 898 QMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALN 957
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 QMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALN 960
Qy 958 TLVKQLSSNFGAISSVLNDILARLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRA 1017
|||||||||||||||||||||:||||||||||||||||||||||||||||||||||||||
Db 961 TLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRA 1020
Qy 1018 SANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPA 1077
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 SANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPA 1080
Qy 1078 ICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTHNTFVSGNCDVVIGIVNNTVYDP 1137
||||||||||||||||||||||||||||||||||||| ||||||||||||||||||||||
Db 1081 ICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDP 1140
Qy 1138 LQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDL 1197
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 LQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDL 1200
Qy 1198 QELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCKFDEDD 1257
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1201 QELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCKFDEDD 1260
Qy 1258 SEPVLKGVKLHYT 1270
|||||||||||||
Db 1261 SEPVLKGVKLHYT 1273
Allowable Subject Matter
The following is a statement of reasons for the indication of allowable subject matter: SEQ ID NOs: 1 and 5 appear to be free of the prior art.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure and is listed below.
Mukhopadhyay et. al. (WO2021178661A1, Pub. 09/10/2021, Priority 03/04/2020; hereafter “Mukhopadhyay”.)(NB: Mukhopadhyay would additionally qualify under 35 U.S.C. 102(a)(1) based on its 09/10/2021 publication date if applicant fails to establish that the rejected claims are entitled to the 08/27/2021 priority date.) Teaches vectors comprising SARS CoV-2 S proteins and molecular adjuvants such as CXCL9 and IL7 separated by P2A elements. Not readily apparent if the SARS CoV-2 S protein sequences comprise D614G mutation. Not utilized as rejection would be redundant to those set forth supra.
US20240042015A1. Teaches vectors comprising SARS CoV-2 S proteins and molecular adjuvants such as IL7 separated by P2A elements. Not readily apparent if the SARS CoV-2 S protein sequences comprise D614G mutation as SEQ ID NO: 325 still comprises the original D614, yet they teach strains that inherently comprise D614G (reference claim 105). Not utilized as rejection would be redundant to those set forth supra.
Jung HE, et. al. Antiviral Res. 2023 Aug;216:105656. Epub 2023 Jun 14. Applicant-related post-filing art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RACHEL B GILL whose telephone number is (571)272-3129. The examiner can normally be reached on M to F 8:00 AM to 5:00 PM Eastern.
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/RACHEL B GILL/
Primary Examiner, Art Unit 1671
Prosecution Insights