DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 06/04/2026 has been entered.
Disposition of Claims
Claims 54, 56-62, and 64-67 were pending. Claims 1-53, 55, 57, 63, 65, and 68 are cancelled. Amendments to claims 54, 58, 62, and 66-67 are acknowledged and entered. Claims 54, 56, 58-62, 64, and 66-67 will be examined on their merits.
Response to Arguments
Applicant's arguments filed 06/04/2026 regarding the previous Office action dated 03/09/2026 have been fully considered. If they have been found to be persuasive, the objection/rejection has been withdrawn below. Likewise, if a rejection/objection has not been recited, said rejection/objection has been withdrawn. If the arguments have not been found to be persuasive, or if there are arguments presented over art that has been utilized in withdrawn rejections but utilized in new rejections, the arguments will be addressed fully with the objection/rejection below.
Examiner’s Note
All paragraph numbers (¶) throughout this office action, unless otherwise noted, are from the US PGPub of this application US20240016919A1, Published 01/18/2024. Amendments to the specification presented on 02/03/2026 are acknowledged and entered.
The Power of Attorney filed on 12/10/2025 is acknowledged and entered.
Claim Rejections - 35 USC § 112(b); Second Paragraph
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
(Rejection withdrawn.) The rejection of Claims 54, 62, and 67 and dependent claims 56-61 and 64-66 thereof under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the amendments to the claims.
(New rejection – necessitated by amendment.) Claims 54, 62, and 67 and dependent claims 56, 58-61, 64, and 66 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.
The dosage of the “low dose” in instant claims 54, 62, and 67 is listed as being 0.2 mg, but it is unclear as to what item(s) in the composition said weight references. For instance, it is unclear if the 0.2 mg refers to the amount of nucleic acid molecule of claim 54, or the total overall weight of the entire composition, or a weight of a certain portion of components (e.g. active ingredient, such as the nucleic acid of claim 54 or the protein of claim 62, and an additional adjuvant, excipient, or carrier). From the guidance in the specification, it appears as though the dosage refers to the MERS-CoV active ingredient, so one claim amendment suggestion is to clarify that the dosage refers to the amount of claimed sequences delivered per dose.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claims 54, 62, and 67 are rejected on the grounds of being indefinite. Claims 56, 58-61, 64, and 66 are also rejected since they depend from claim 54, 62, or 67, but does not remedy these deficiencies of claim 54, 62, or 67.
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 54 is drawn to a method of inducing an immune response against a Middle East Respiratory syndrome (MERS) coronavirus (MERS-CoV) in a subject in need thereof, the method comprising administering an immunogenic composition intradermally to the subject, wherein the immunogenic composition is administrated at a low dose, wherein the low dose is 0.2 mg, wherein the immunogenic composition is administered twice, wherein the immunogenic composition comprises a nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of:
a) an immunogenic fragment of SEQ ID NO: 1, wherein the fragment encodes a sequence having 100% identity to consecutive amino acids over at least 60% of the full length of SEQ ID NO:2;
b) an immunogenic fragment of SEQ ID NO:3, wherein the fragment encodes a sequence having 100% identity to consecutive amino acids over at least 60% of the full length of SEQ ID NO:4;
c) a nucleotide sequence having at least 90% identity over an entire length of the nucleic acid sequence set forth in SEQ ID NO: 1;
d) a nucleotide sequence having at least 90% identity over an entire length of the nucleic acid sequence set forth in SEQ ID NO:3;
e) an immunogenic fragment of SEQ ID NO: 1, wherein the fragment comprises a sequence having 100% identity to consecutive bases over at least 60% of the full length of SEQ ID NO:1; and
f) an immunogenic fragment of SEQ ID NO:3, wherein the fragment comprises a sequence having 100% identity to consecutive bases over at least 60% of the full length of SEQ ID NO:3.
Further limitations on the method of claim 54 are wherein the method of administering further comprises an electroporation step (claim 56); wherein the second administration of the immunogenic composition is given at least 7 days after the first administration (claim 58); wherein the nucleic acid molecule comprises an expression vector (claim 59);wherein the immunogenic composition further comprises a pharmaceutically acceptable excipient, an adjuvant, or a combination thereof (claim 60); and wherein the immune response is protective or therapeutic (claim 61).
Claim 62 is drawn to a method of inducing an immune response against a Middle East Respiratory Syndrome coronavirus (MERS-CoV) in a subject in need thereof, the method comprising administering an immunogenic composition intradermally to the subject, wherein the immunogenic composition is administrated at a low dose, wherein the low dose is 0.2 mg, wherein the immunogenic composition is administered twice, wherein the immunogenic composition comprises an antigen comprising an amino acid sequence selected from the group consisting of:
a) an amino acid sequence as set forth in SEQ ID NO:2;
b) an amino acid sequence as set forth in SEQ ID NO:4;
c) a fragment of SEQ ID NO:2 lacking the IgE leader sequence as set forth by SEQ ID NO:6; and
d) a fragment of SEQ ID NO:4 lacking the IgE leader sequence as set forth by SEQ ID NO:6.
Further limitations on the method of claim 62 are wherein the method of administering is intradermal administration (claim 63); wherein the method of administering further comprises an electroporation step (claim 64); and wherein the second administration of the immunogenic composition is given at least 7 days after the first administration (claim 66).
Claim 67 is drawn to an intradermal vaccine comprising an immunogenic composition, wherein the vaccine is formulated for administration as a low-dose formula, wherein the low-dose formula is 0.2 mg, wherein the vaccine is administered twice, wherein the immunogenic composition comprises a nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of:
a) an immunogenic fragment of SEQ ID NO: 1, wherein the fragment encodes a sequence having 100% identity to consecutive amino acids over at least 60% of the full length of SEQ ID NO:2;
b) an immunogenic fragment of SEQ ID NO:3, wherein the fragment encodes a sequence having 100% identity to consecutive amino acids over at least 60% of the full length of SEQ ID NO:4;
c) a nucleotide sequence having at least 90% identity over an entire length of the nucleic acid sequence set forth in SEQ ID NO: 1;
d) a nucleotide sequence having at least 90% identity over an entire length of the nucleic acid sequence set forth in SEQ ID NO:3;
e) an immunogenic fragment of SEQ ID NO:1, wherein the fragment comprises a sequence having 100% identity to consecutive bases over at least 60% of the full length of SEQ ID NO:1; and
f) an immunogenic fragment of SEQ ID NO:3, wherein the fragment comprises a sequence having 100% identity to consecutive bases over at least 60% of the full length of SEQ ID NO:3.
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.
(New rejection.) Claim 61 is 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 prophylactic protection of rhesus macaques administered a 0.2 mg MERS-CoV DNA vaccine intradermally twice, four weeks apart, followed by adaptive electroporation, does not reasonably provide enablement for administering the fixed 0.2 mg dosage regimen to the full breadth of the claimed subjects to elicit a protective or therapeutic immune response. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The legal considerations that govern enablement determinations pertaining to undue experimentation have been set forth in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). The factors to be considered include: (1) the breadth of the claims; (2) the nature of the invention; (3) the state of the prior art; (4) the level of one of ordinary skill; (5) the level of predictability in the art; (6) the amount of direction provided by the inventor; (7) the existence of working examples; and (8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure. The factors are considered as a whole in determining whether any necessary experimentation would have been undue.
Nature of the invention and breadth of the claims. Claim 61 is directed to inducing a protective or therapeutic immune response against MERS-CoV by administering a 0.2 mg dose of the claimed immunogenic composition intradermally on two occasions. The specification demonstrates prophylactic protection in rhesus macaques administered the 0.2 mg dose twice, four weeks apart, followed by adaptive electroporation (¶[0163-0175]). However, claim 61 is not limited to the disclosed rhesus macaque, prophylactic administration, or intradermal administration followed by electroporation embodiments, as the claim also encompasses a broader array of subjects, in that said subjects may be a human, horse, cow, pig, sheep, cat, dog, rat, or mouse (¶[0133]). The claimed scope therefore extends beyond the embodiments described in the specification, as it encompasses the use of a fixed 0.2 mg dosing regimen across materially different subjects while requiring a protective or therapeutic result.
State of the prior art and predictability of the art. At the time the application was filed, it was known that MERS-CoV immunogens, such as the spike (S) protein, could be delivered via intradermal means, followed by electroporation, at set doses, such as 200 ug (See Graham et. al. US20180244756A1 at ¶[0364-0365]). Graham further states “[t]he dosage and number of doses will depend on the setting, for example, in an adult or anyone primed by prior MERS-CoV infection or immunization” (¶[0366]), however, Graham clarifies that amounts effective to treat, inhibit, or prevent infection depend on “the severity of the disease, the general state of the subject's health, and the robustness of the subject's immune system.”(¶[0368]).
McCluskie et. al. (McCluskie MJ, et. al. Mol Med. 1999 May;5(5):287-300.) compared DNA vaccine administration in mice and rhesus macaques. McCluskie reported that results in mice were not always predictive of results in monkeys, and stated that “[o]ptimal dose and immunization schedule will most likely vary between species. It is not clear whether results in non-human primates will be predictive of results in humans, thus additional studies are required.”
Zehrung et. al. (Zehrung D, et. al. Vaccine. 2013 Jul 25;31(34):3392-5. Epub 2012 Nov 20.) notes issues with intradermal delivery (ID) of vaccines, such as establishing the optimal doses for different vaccines and reformulating to adjust antigen concentration or add preservatives (abstract). Zehrung notes that clinical data shows that dose sparing via ID vaccination can be achieved with “some but not all vaccines” and that “[t]he immunological advantage of ID delivery varies between vaccines. It cannot be assumed that reduced-dose ID delivery will be safe and effective for all vaccines or populations. The optimum dose for target populations will need to be established in high-quality clinical trials, and the effectiveness of reduced-dose immunization will need to be monitored after introduction to confirm that long-lasting immunity is induced.”
The art therefore would not have supported extrapolation from a prophylactic 0.2 mg intradermal/electroporation double dose vaccination regimen in rhesus macaques to the full scope of subjects encompassed by claim 61, particularly where the claim requires a protective or therapeutic outcome and does not require electroporation.
Working examples, guidance, and necessary experimentation. The specification provides one working example demonstrating prophylactic protection in rhesus macaques (Example 1 starting at ¶[0163]). The specification does not provide any working examples demonstrating that the fixed 0.2 mg dosage regimen elicits a protective or therapeutic response in the other encompassed subjects or provides a therapeutic effect after infection. All intradermal inoculations appear to have been followed by electroporation.
The specification acknowledges that an effective dose depends on the vaccine regimen, manner of administration, stage and severity of disease, general health of the patient, and judgment of the prescribing physician (¶[0134]). To practice the full scope of claim 61, one skilled in the art would need to perform additional dose-ranging and efficacy studies to determine whether the fixed 0.2 mg regimen elicits the claimed protective or therapeutic response in the encompassed subjects, with and without electroporation. The required experimentation would not merely confirm results reasonably expected from the disclosure.
Conclusion. For the reasons discussed above, the specification does not enable one skilled in the art to use the full scope of the invention recited in claim 61 without undue experimentation.
(New rejection.) Claims 62, 64, and 66 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 intradermal administration with adaptive electroporation of a 0.2 mg MERS-CoV DNA vaccine delivered twice to rhesus macaques, does not reasonably provide enablement for directly administering a fixed 0.2 mg dose of the claimed protein antigen to the full breadth of subjects to induce an immune response against MERS-CoV. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The legal considerations that govern enablement determinations pertaining to undue experimentation have been set forth in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). The factors to be considered include: (1) the breadth of the claims; (2) the nature of the invention; (3) the state of the prior art; (4) the level of one of ordinary skill; (5) the level of predictability in the art; (6) the amount of direction provided by the inventor; (7) the existence of working examples; and (8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure. The factors are considered as a whole in determining whether any necessary experimentation would have been undue.
Nature of the invention and breadth of the claims. The claimed invention is directed to inducing an immune response against MERS-CoV by twice administering a protein antigen comprising SEQ ID NO: 2, SEQ ID NO: 4, or a recited fragment thereof at a fixed low dose of 0.2 mg. Claim 64 further requires electroporation, and claim 66 further limits the interval between the first and second administrations.
The specification does not provide a working example directed to the direct administration of isolated or otherwise expressed protein antigen. Instead, the specification administers a synthetic DNA vaccine encoding a full-length MERS-CoV spike antigen. Rhesus macaques received 0.2 mg of the MERS DNA vaccine intradermally, followed by adaptive electroporation, in a two-dose regimen spaced four weeks apart (See Example 1 at ¶[0163]).
The claims are broader than the tested embodiment. They apply the same numerical dose to a different vaccine platform and encompass subjects of different species, wherein the species are of different sizes and physiological characteristics (¶[0048]). The claimed scope therefore extends beyond the embodiments described in the specification.
State of the prior art and predictability of the art. At the time the application was filed, it was known that MERS-CoV immunogens, such as the spike (S) protein, could be delivered via intradermal means, followed by electroporation, at set doses, such as 200 ug (See Graham et. al. US20180244756A1 at ¶[0364-0365]). Graham further states “[t]he dosage and number of doses will depend on the setting, for example, in an adult or anyone primed by prior MERS-CoV infection or immunization” (¶[0366]) and that amounts effective to treat, inhibit, or prevent infection depend on “the severity of the disease, the general state of the subject's health, and the robustness of the subject's immune system.”(¶[0368]).
Lan et. al. (Lan J, et. al. PLoS One. 2014 Nov 18;9(11):e112602.) states that highly purified proteins are “typically not inherently immunogenic” and that their inability to stimulate a response is because “they usually lack the means to directly stimulate the innate immune system” and are “often prone to degradation”, which means they “call for efficient delivery systems and potent immunostimulants, jointly denoted as adjuvant(s) to evoke the desired antigen-specific immune response phenotype enabling successful vaccination.” Lan tested a MERS-CoV receptor binding domain (RBD) protein vaccine using different adjuvant formulations and routes of administration and found that the resulting immune response could be tailored by those choices (See entire document; abstract; Introduction), but that certain adjuvant combinations could mask or destroy important target sites on the antigen (Discussion).
Yong et. al. (Yong CY, et. al. Front Microbiol. 2019 Aug 2;10:1781.) distinguishes DNA vaccines from subunit protein vaccines as separate MERS-CoV vaccine platforms. Yong explains that subunit vaccines are often administered with adjuvants to increase recombinant antigen immunogenicity, while DNA vaccine administration often requires an external device such as an electroporator. Yong also notes the safety issues associated with delivery of MERS-CoV full-length S protein, in that MERS-CoV vaccine candidates against SARS CoV were initially developed based on the full-length S protein, but these vaccines were later demonstrated to induce non-neutralizing antibodies which did not prevent MERS-CoV infection, and the immunized animals were not protected from the viral challenge and they instead experienced adverse effects like enhanced hepatitis, increased morbidity, and stronger inflammatory responses (p. 3, left col.).
The art therefore would not have supported extrapolation from a 0.2 mg DNA vaccine dose delivered via intradermal/electroporation means in rhesus macaques to direct administration of a fixed 0.2 mg protein antigen dose across the full claimed scope.
Working examples, guidance, and necessary experimentation. The specification provides one working example demonstrating prophylactic protection in rhesus macaques (Example 1 starting at ¶[0163]). The specification does not provide any working examples demonstrating that the fixed 0.2 mg dosage regimen of a directly administered protein antigen elicits a protective or therapeutic response in the other encompassed subjects or provides a therapeutic effect after infection. Additionally, the specification fails to show whether electroporation provides an added benefit when the administered material is protein rather than antigen-encoding DNA.
To practice the full scope of claims 62, 64, and 66, one skilled in the art would need to prepare the claimed proteins and test dosing, formulation, adjuvant use, and delivery conditions in the encompassed subjects. Such experimentation would be needed to determine whether the fixed 0.2 mg protein-antigen dose elicits the claimed immune response. The existence of known assays does not establish that the operative protein-vaccine embodiments could be identified without undue experimentation.
Conclusion. For the reasons discussed above, the specification does not enable one skilled in the art to use the full scope of the invention recited in claims 62, 64, and 66 without undue experimentation.
Claim Rejections - 35 USC § 102
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
(Rejection withdrawn.) The rejection of Claims 54, 56-62, and 64-67 under 35 U.S.C. 102(a)(1) as being anticipated by Weiner et. al. (US20170258893A1; Pub. 09/14/2017; hereafter “Weiner”) is withdrawn in light of the amendments to the claims.
Claim Rejections - 35 USC § 103
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 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
(New rejection.) Claims 54, 56, 58-62, 64, and 66-67 are rejected under 35 U.S.C. 103 as being unpatentable over Weiner et. al. (US20170258893A1; Pub. 09/14/2017; hereafter “Weiner”) in view of Graham et. al. (US20180244756A1, Pub. 08/30/2018; hereafter “Graham”.)
The Prior Art
Weiner teaches vaccine compositions comprising Middle East Respiratory Syndrome coronavirus (MERS-CoV) antigens, such as consensus spike (S) antigens, and methods of administering said compositions to a subject in need thereof (entire document; see abstract.) Weiner teaches SEQ ID NO: 1, which aligns with 100% identity to instant SEQ ID NO:1, which is a consensus sequence for MERS CoV spike (S) protein, and encodes SEQ ID NO:2, which is 100% identical to instant SEQ ID NO:2 (¶[0102]). Weiner also teaches SEQ ID NO: 3, which aligns with 100% identity to instant SEQ ID NO: 3, and is a MERS-CoV consensus spike antigen lacking the cytoplasmic domain (ΔCD) which encodes SEQ ID NO:4 (¶[0110]). Weiner teaches that the compositions would be used in methods of inducing a prophylactic or therapeutic immune response against a in a subject in need thereof (¶[0138-0143]), the method comprising administering an immunogenic composition intradermally to the subject (¶[0092][0144-0147][0183]), wherein the immunogenic composition comprises a nucleic acid molecule, wherein the nucleic acid molecule comprises a nucleic acid sequence having at least about 90% identity over an entire length of the nucleic acid sequence set forth in SEQ ID NO:1 (¶[0120][0172-0173]), and shows that a low dose formulation comprised delivery of 0.5 mg/animal (¶[0043][0248-0250]) and that the vaccine dose may be between 1 ug to 10 mg active component/kg body weight or between 20 ug to 10 mg active component/kg body weight (¶[0140]). Weiner teaches the nucleic acid molecule comprises an expression vector (¶[0122-0126][0144]; instant claim 59). Weiner teaches the composition may comprise a pharmaceutically acceptable excipient (reference claim 15) and an adjuvant (reference claim 16; instant claim 60.) Weiner teaches the vaccine may further comprise a peptide comprising an amino acid sequence having at least about 90% identity over an entire length of the amino acid sequence set forth in SEQ ID NO: 2 or SEQ ID NO: 4 (¶[0258]). The peptides of the composition may be an immunogenic fragment of SEQ ID NO: 2 or 4 and may comprise or lack an IgE leader sequence (¶[0104-0106]). Weiner teaches the intradermal administration comprises electroporation or injection (¶[0285][0287][0289]; instant claims 56, 64). Weiner teaches the administration can be followed by boosting administrations, such as a prime on day 0 and a boost on days 14 and 28 (¶[0183]; instant claims 58, 66). Weiner teaches the amount required to raise the desired immune response is a “therapeutically effective dose” (¶[0143]) and can be between 1 ug to 10 mg active component per kg body weight/time (¶[0140]).
While Weiner teaches the majority of the limitations of the instantly claimed invention, and teaches a dosage for delivery, Weiner is silent as to the specific dosage delivered being 0.2 mg, such a dosage would be obvious to a skilled artisan, especially given the teachings of Graham.
Graham teaches methods of inducing an immune response in a subject to the Middle East respiratory syndrome coronavirus (MERS-CoV), wherein the immune response is a protective immune response that inhibits or prevents MERS-CoV infection in the subject. Graham teaches recombinant MERS-CoV polypeptides and nucleic acid molecules encoding same (entire document; see abstract.) Graham teaches administration of the MERS-CoV S protein as either a nucleic acid or protein (reference claim 1; ¶[0005]), wherein the S protein can be a full-length protein or a fragment thereof, such as a fragment comprising the receptor binding domain (RBD) of the S protein, fragments lacking the S2 domain, or fragments lacking the transmembrane (TM) and cytoplasmic domains (¶[0006][0009]; Fig. 1). Graham teaches the S protein can be a consensus antigen, and may include codon optimization, RNA optimization, or other structural supports to maintain the stability of the MERS-CoV S construct (¶[0087]). Graham teaches that the construct may be within an immunogenic composition (¶[0109-0110]), and can be administered as a prime/boost vaccine (¶[0132]). The composition may be administered intradermally (¶[0054][0399]), and a therapeutically effective amount of the immunogen, whether the immunogen is the MERS CoV S protein, immunogenic fragment thereof, polynucleotides encoding same, protein nanoparticles, viral-like particles, or vectors, can be delivered at a dosage of about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250, or about 300 μg (¶[0365]). Graham teaches plasmid vaccines were constructed that encoded different constructs of MERS-CoV S, wherein the plasmids were administered to the mice via injection followed by electroporation (¶[0013][0101][0421][0435][0453][0456]; instant claims 56, 64). Graham teaches different prime/boost vaccination regimens, wherein the second booster dose was delivered at week 3 (¶[0009]) or week 4 (¶[0013]), but the timing and dosage can be adjusted according to the therapeutic agent and subject (¶[0300][0361][0376]; instant claims 58, 66). Graham teaches expression vectors which are capable of expressing the MERS-CoV S protein (¶[0134][0384][0438]; instant claim 59). Graham teaches the immunogenic composition can further comprise a pharmaceutically acceptable carrier, an adjuvant, or a combination thereof (¶[0053][0110]; instant claim 60). Graham teaches that the immune response elicited may be protective/prophylactic or therapeutic (¶[0150-0151][0156]; instant claim 61).
Given the teachings of Weiner and Graham, one of skill in the art would be apprised as to vaccine compositions comprising MERS CoV S antigens and methods of intradermal administration thereof. Given the teachings of Weiner, one of skill in the art would be apprised as to specific MERS-CoV S protein consensus nucleic acid sequences and consensus proteins encoded therefrom. Given the teachings from both Weiner and Graham, one of skill in the art would be apprised as to prime/boost vaccination regimens, methods of intradermal administration, and the use of electroporation to enhance nucleic acid delivery of vaccine compositions. Given the teachings of Graham, one of skill in the art would be apprised as to general vaccine concentrations for overall delivery, such as delivery amounts of 0.2 mg (200 ug). Therefore, arriving at the limitations of instant claims 54, 62, and 67 would be obvious to a skilled artisan given the combined and highly related teachings of Weiner and Graham.
It would have been obvious to one of ordinary skill in the art to modify the methods and compositions taught by Weiner in order to deliver a therapeutically effective intradermal dose of the MERS-CoV S antigen vaccine. One would have been motivated to do so, given the suggestion by Graham that the immunogenic compositions could be delivered at a dosage of 200 ug, and given that Graham expressly identifies the claimed route, dosage, and multiple-dose regimen as suitable vaccination parameters. One of skill in the art would have had a reasonable expectation that the modified method would induce an immune response against MERS-CoV because Graham demonstrates that prime-boost regimens of MERS-CoV S1 antigens elicit neutralizing antibodies. 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.
Response to Arguments
Applicant's arguments filed 06/04/2026 have been fully considered but they are not entirely persuasive.
While the original 35 USC 102 over Weiner has been withdrawn as noted supra, as it was persuasive that Weiner failed to teach the exact 0.2 mg dosage, it remains that Weiner still teaches the majority of the instantly claimed limitations, and arriving at the 0.2 mg dosage would have been obvious to a skilled artisan, especially given the highly related teachings of Graham, detailed supra in the new 35 USC 103 rejection. Therefore, while Weiner may not anticipate the instant claims, Weiner still renders obvious the instant claims.
Double Patenting
The text regarding nonstatutory double patenting was presented in a previous Office action.
(Rejection withdrawn.) The rejection of Claims 54, 56-62, and 64-67 on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 10,016,497 in view of Weiner (supra) is withdrawn in light of the amendments to the claims.
(Rejection withdrawn.) The rejection of Claims 54, 56-62, and 64-67 on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 10,548,971 in view of Weiner (supra) is withdrawn in light of the amendments to the claims.
(Rejection withdrawn.) The rejection of Claims 54, 56-62, and 64-67 on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11,135,284 in view of Weiner (supra) is withdrawn in light of the amendments to the claims.
(Rejection withdrawn.) The rejection of Claims 54, 56-62, and 64-67 on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 11,801,298 in view of Weiner (supra) is withdrawn in light of the amendments to the claims.
(Rejection withdrawn.) The provisional rejection of Claims 54, 56-62, and 64-67 on the ground of nonstatutory double patenting as being unpatentable over claims 36-42 of copending Application No. 18/476,921 in view of Weiner (supra) is withdrawn in light of the abandonment of the ‘921 application.
(New rejection.) Claims 54, 56, 58-62, 64, and 66-67 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 10,016,497 in view of Weiner and Graham (supra).
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to immunogenic compositions which comprise nucleic acid sequences of SEQ ID NO: 1 or 3 which encode protein sequences of SEQ ID NOs: 2 or 4, respectively. Both sets of claims are drawn to the compositions further comprising peptides of SEQ ID NOs: 2 or 4, both are drawn to the nucleic acid molecules being within an expression vector, or incorporated into a viral particle. Both sets of claims are drawn to the compositions comprising pharmaceutically acceptable excipients or adjuvants. Both sets of claims are drawn to methods of prophylactically or therapeutically treating a subject in need thereof against a MERS CoV infection, wherein the method may comprise injection or electroporation. The main difference is that the instant claims provide that the method of delivery of the immunogenic composition may be intradermally at a 0.2 mg dose; however, said concentrations and methods of administration of such a composition were well-known to a skilled artisan, as evidenced by the teachings of Weiner and Graham (NB: while Weiner is the PGPub of the ‘497 patent, the PGPub qualifies as prior art to the instant claims and speaks to the obvious nature of the variations between the instant claims and the ‘497 claims.) Weiner teaches immunogenic compositions which comprise nucleic acids comprising SEQ ID NOs: 1 or 3, which encode SEQ ID NOs: 2 or 4, and Weiner teaches that the compositions may be delivered intradermally to a subject in need thereof to therapeutically inhibit MERS CoV infection, while Graham teaches administration of MERS-CoV S antigen compositions at the 0.2 mg dose, and that dosage of the MERS-CoV S antigen in prime/boost vaccination regimens can elicit neutralizing antibodies (see detailed teachings of Weiner and Graham outlined supra.) Therefore, the differences between the instant claims and the ‘497 claims would be obvious to a skilled artisan, especially in light of the teachings of Weiner and Graham, and are not patentably distinct.
(New rejection.) Claims 54, 56, 58-62, 64, and 66-67 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 10,548,971 in view of Weiner and Graham (supra).
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to immunogenic compositions which comprise nucleic acid sequences of SEQ ID NO: 1 or 3 which encode protein sequences of SEQ ID NOs: 2 or 4, respectively. Both sets of claims are drawn to the compositions further comprising peptides of SEQ ID NOs: 2 or 4, both are drawn to the nucleic acid molecules being within an expression vector, or incorporated into a viral particle. Both sets of claims are drawn to the compositions comprising pharmaceutically acceptable excipients or adjuvants. Both sets of claims are drawn to methods of prophylactically or therapeutically treating a subject in need thereof against a MERS CoV infection, wherein the method may comprise injection or electroporation. The main difference is that the instant claims provide that the method of delivery of the immunogenic composition may be intradermally at a 0.2 mg dose; however, said concentrations and methods of administration of such a composition were well-known to a skilled artisan, as evidenced by the teachings of Weiner and Graham (NB: while Weiner is the PGPub of the ‘497 patent, the PGPub qualifies as prior art to the instant claims and speaks to the obvious nature of the variations between the instant claims and the ‘971 claims.) Weiner teaches immunogenic compositions which comprise nucleic acids comprising SEQ ID NOs: 1 or 3, which encode SEQ ID NOs: 2 or 4, and Weiner teaches that the compositions may be delivered intradermally to a subject in need thereof to therapeutically inhibit MERS CoV infection, while Graham teaches administration of MERS-CoV S antigen compositions at the 0.2 mg dose, and that dosage of the MERS-CoV S antigen in prime/boost vaccination regimens can elicit neutralizing antibodies (see detailed teachings of Weiner and Graham outlined supra.) Therefore, the differences between the instant claims and the ‘971 claims would be obvious to a skilled artisan, especially in light of the teachings of Weiner and Graham, and are not patentably distinct.
(New rejection.) Claims 54, 56, 58-62, 64, and 66-67 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11,135,284 in view of Weiner and Graham (supra).
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to immunogenic compositions which comprise nucleic acid sequences of SEQ ID NO: 1 or 3 which encode protein sequences of SEQ ID NOs: 2 or 4, respectively. Both sets of claims are drawn to the compositions further comprising peptides of SEQ ID NOs: 2 or 4, both are drawn to the nucleic acid molecules being within an expression vector, or incorporated into a viral particle. Both sets of claims are drawn to the compositions comprising pharmaceutically acceptable excipients or adjuvants. Both sets of claims are drawn to methods of prophylactically or therapeutically treating a subject in need thereof against a MERS CoV infection, wherein the method may comprise injection or electroporation. The main difference is that the instant claims provide that the method of delivery of the immunogenic composition may be intradermally at a low dose; however, said methods of administration of such a composition were well-known to a skilled artisan, as evidenced by the teachings of Weiner (NB: while Weiner is the PGPub of the ‘497 parent patent, the PGPub qualifies as prior art to the instant claims and speaks to the obvious nature of the variations between the instant claims and the ‘284 claims.) Weiner teaches immunogenic compositions which comprise nucleic acids comprising SEQ ID NOs: 1 or 3, which encode SEQ ID NOs: 2 or 4, and Weiner teaches that the compositions may be delivered intradermally to a subject in need thereof to therapeutically inhibit MERS CoV infection, while Graham teaches administration of MERS-CoV S antigen compositions at the 0.2 mg dose, and that dosage of the MERS-CoV S antigen in prime/boost vaccination regimens can elicit neutralizing antibodies (see detailed teachings of Weiner and Graham outlined supra.) Therefore, the differences between the instant claims and the ‘284 claims would be obvious to a skilled artisan, especially in light of the teachings of Weiner and Graham, and are not patentably distinct.
(New rejection.) Claims 54, 56, 58-62, 64, and 66-67 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 11,801,298 in view of Weiner and Graham (supra).
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to methods of delivering immunogenic compositions which comprise protein sequences of SEQ ID NOs: 2 or 4, respectively. Both sets of claims are drawn to methods of prophylactically or therapeutically treating a subject in need thereof against a MERS CoV infection, wherein the method may comprise injection or electroporation. The main difference is that the instant claims are drawn to the compositions which comprise nucleic acids which also encode said proteins of SEQ ID NOs: 2 or 4, and the instant claims provide that the method of delivery of the immunogenic composition is intradermally at a low dose; however, said method and dosage of administration of such a composition were well-known to a skilled artisan, as evidenced by the teachings of Weiner and Graham (NB: while Weiner is the PGPub of the ‘497 parent patent, the PGPub qualifies as prior art to the instant claims and speaks to the obvious nature of the variations between the instant claims and the ‘298 claims.) Weiner teaches immunogenic compositions which comprise nucleic acids comprising SEQ ID NOs: 1 or 3, which encode SEQ ID NOs: 2 or 4, and Weiner teaches that the compositions may be delivered intradermally to a subject in need thereof to therapeutically inhibit MERS CoV infection, while Graham teaches administration of MERS-CoV S antigen compositions at the 0.2 mg dose, and that dosage of the MERS-CoV S antigen in prime/boost vaccination regimens can elicit neutralizing antibodies (see detailed teachings of Weiner and Graham outlined supra.) Therefore, the differences between the instant claims and the ‘298 claims would be obvious to a skilled artisan, especially in light of the teachings of Weiner and Graham, and are not patentably distinct.
Response to Arguments
Applicant's arguments filed 06/04/2026 have been fully considered but they are not entirely persuasive.
Applicant repeats many of the same arguments regarding Weiner. While the original NSDP rejection was withdrawn, a new rejection incorporating the teachings of Graham and Weiner is presented herein, to show the obvious nature of the claimed subject matter and that delivering highly similar compositions at the dosage of the instant claims was taught in the prior art.
For the reasons set forth supra and in the previous Office action, the instant pending claims stand rejected over the noted patent claims and copending claims.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
WO2021178661A1. Teaches intradermal electroporation delivery of coronavirus DNA vaccine compositions, such as MERS CoV, at 0.25-1 mg of a nucleic acid, or at 0.1-3 mg. Not utilized as rejection would be redundant to those set forth supra.
Agnes JT, et. al. Front Immunol. 2025 Nov 14;16:1662923. Post-filing art related to the instant invention. Showed dosage at higher amount was superior to low-dose vaccination.
US20220087930A1. Teaches intradermal electroporation prime/boost delivery of coronavirus DNA vaccine compositions, such as SARS-CoV 2 and MERS CoV. Provides motivation for low dose/dose sparing. Not utilized as rejection would be redundant to those set forth supra.
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.
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 on (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.
/RACHEL B GILL/
Primary Examiner, Art Unit 1671
Prosecution Insights