Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Information Disclosure Statement
The information disclosure statements (IDS) filed 10/23/2023, 01/30/2024, 10/25/2024, 03/04/2025, and 07/30/2025 have been considered and the references therein are of record.
Claim Objections
Claim 4 is objected to because of the following informality: contains a grammatical error, reciting “of of”.
Claims 9-13, 15, and 19 are objected to because of the following informalities: contains a spelling error, reciting, "eptide"; "peptide" should be inserted.
Claim 18 is objected to because of the following informality: contains an error, reciting, “µg mg”. For purposes of compact prosecution, this error will be interpreted as “µg”.
Claim 19 is objected to because of the following informalities: contains a spelling error, reciting “plagues”, and a grammatical error, reciting “locally directly”. For the purposes of compact prosecution, these errors will be interpreted as “locally administer directly to atherosclerotic plaques using micro catheters.”
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 3, 7, and 15-19 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 claims contain 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.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant has possession of and what Applicant is claiming. Claims 3, 7, and 15-19 recite a vaccine with a nucleotide sequence comprising one or more modifications to the ribose sugar, the nucleotide base, the 5′-terminus, the 3′-terminus, or combinations thereof (claim 3); a vaccine with a polypeptide sequence comprising one or more modifications to the peptide backbone, the amino acid side chains, the N-terminus, the C-terminus, or combinations thereof (claim 7); and a method of administering a vaccine composition to treat atherothrombosis (claims 15-19), each of which encompasses a genus of agents.
Claims 3 and 7 do not require that the genera of the claims possess any particular structure or other distinguishing feature that is characteristic of the genera as a whole. Therefore claims 3 and 7 are drawn to a genus of modified vaccines for which there is inadequate written description. Claims 15-19, while requiring the particular structure of SEQ ID NO: 5-16, are not sufficiently supported by the specification that the applicant is in possession of the claim genera at the time of filing.
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 (see MPEP 2163(II)(3)(a)(i)(A), reduction to drawings MPEP 2163(II)(3)(a)(i)(B), 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 MPEP 2163(II)(3)(a)(i)(C).
Regarding the genera of the claims 3 and 7, the specification describes a limited set of RNA modifications that fall within the genus claimed (Spec. [0116-0117]). The claims, however are not limited to those species but also includes any modification to an RNA ribose sugar, nucleotide base, 5′-terminus, 3′-terminus, or combinations thereof and any modification to a peptide backbone, amino acid side chains, N-terminus, C-terminus, or combinations thereof, which encompasses a vast array of agents, and the specification fails to provide a representative number of species within the recited genus. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics of the genus as a whole, or representative number of species within the genus, the specification does not provide adequate written description of the claimed genus.
Regarding the genera of the claims 15-19, the specification describes zero species that fall within the genus claimed. The specification provides no evidence that the Applicant was in possession of a vaccine composition that is capable of treating atherothrombosis. As such, the specification fails to provide a representative number of species within the recited genus. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics of the genus as a whole, or representative number of species within the genus, the specification does not provide adequate written description of the claimed genus.
Claims 3, 7, and 15-19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a limited set of RNA modifications (Spec. [0116-0117]), does not reasonably provide enablement for the genera of a vaccine with a nucleotide sequence comprising SEQ ID NO: 5, 7, 9, 11, or 13–16, as well as one or more modifications to the ribose sugar, the nucleotide base, the 5′-terminus, the 3′-terminus, or combinations thereof (claim 3); a vaccine with a polypeptide sequence comprising SEQ ID NO: 6, 8, 10, or 12, as well as one or more modifications to the peptide backbone, the amino acid side chains, the N-terminus, the C-terminus, or combinations thereof (claim 7); and a method of administering the RNA or peptide vaccine composition to treat atherothrombosis (claim 15-19). 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 use the invention commensurate in scope with these claims.
The factors to be considered in determining whether a disclosure would require undue experimentation include:
A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 8 USPQ2d, 1400 (CAFC 1988) and MPEP 2164.01.
The breadth of the claims:
With respect to claim breadth, the standard under 35 U.S.C. §112, first paragraph, entails the determination of what the claims recite and what the claims mean as a whole. As such, the broadest reasonable interpretation of the claimed composition is that it covers virtually any modification to the RNA and peptide sequences of the vaccine. The broadest reasonable interpretation of the claimed method is that it covers administration of the claimed vaccine to treat atherothrombosis, where “’treatment’ or ‘treating’ refers to prophylaxis of, preventing, suppressing, repressing, reversing, alleviating, ameliorating, or inhibiting the progress of biological process including a disorder or disease, or completely eliminating a disease (Spec para[0035]).” A skilled artisan would not know how to make the composition and use the method with a reasonable expectation of success based solely on what is disclosed in the specification.
The amount of direction provided by the inventor and the level of predictability in the art:
The specification teaches species of RNA modifications: “RNA synthesized to include 2′-O-methylated ribose, 5-methyl-uridines, or pseudouridine nucleosides do not activate the oligoadenylate synthase (OAS) sensing pathway and induction of the RNase L nuclease resulting in more durable translation of the mRNA vaccine. Synthetic mRNA with a 5′-end modification, a 5′-CAP, confers greater mRNA vaccine stability and enhanced translatability. The natural cap structure is an N7-methylated guanosine (m7G) connected by a 5′-to 5′-O-triphospohate bridge. In some cases, a 2′-O-methylation of the +1 nucleotide ribose results in a cap structure m7GpppN2′OmeN. The synthesis of the natural cap can be complex and an alternate synthetic “CleanCap AG trimer” (TriLink Biotechologies, cat no. N-7113) can be added in vitro using a T7 RNA polymerase.” (Spec page 20). The specification does not provide direction for modifications to the peptide vaccine. The art at the time of filing does not provide enabling guidance for any and all potential modifications to the RNA and peptide sequences of the vaccine. The specification as filed does not provide guidance that overcomes this unpredictability within the art.
The specification does not provide direction as to how the claim method is capable of preventing, suppressing, repressing, reversing, alleviating, ameliorating, or inhibiting the progress of the biological process of atherothrombosis by administering the claimed vaccine composition. Amirfakhryan et al., 2020 teaches that many trials have been conducted on vaccination for atherosclerosis, including vaccines against TNF-α to produce neutralizing antibodies against TNF-α with varying success (Role of Immune System in Atherosclerosis, Vaccination; Table 1-2). Amirfakhryan teaches that the method of vaccination against atherosclerosis “is not as simple and easy as it looks at the first glance” due to the disease being “a multifactorial, chronic, and complex process” (Background). Amirfakhryan teaches that the field is “still in its infancy” (Background). Amirfakhryan teaches that “there is a long distance to reach the ideal vaccination strategy, which could be utilized from early years of life to protect humans against atherosclerosis. It will not be achieved unless the investigators make inexhaustible attempts” (Conclusion). Amirfakhryan teaches that there are additional challenges to the development of a vaccine against atherothrombosis, “such as choice of formulation and route of delivery, vaccine safety and stability, schedule and durability of immunization, proper determination and monitoring of efficacy endpoints in clinical studies, potential side effects of immunization such as undesirable immune activation, and proper selection of population for testing, all need to be addressed in early safety trials (Conclusion).” The art at the time of filing does not provide enabling guidance for using the claimed vaccine composition to treat atherothrombosis. The specification as filed does not provide guidance that overcomes this unpredictability within the art, as it provides no evidence that the claimed vaccine can treat atherothrombosis.
The existence of working examples:
What is enabled by the working examples is narrow in comparison to the breadth of the claims: the specification discloses no working examples.
The quantity of experimentation needed to make or use the invention:
The standard of an enabling disclosure is not the ability to make and test if the invention works but one of the ability to make and use with a reasonable expectation of success. A patent is granted for a completed invention, not the general suggestion of an idea and how that idea might be developed into the claimed invention. In the decision of Genentec, Inc., V. Novo Nordisk, 42 USPQ 2d 100, (CAFC 1997), the court held that: "[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable" and that "[t]ossing out the mere germ of an idea does not constitute enabling disclosure". The court further stated that "when there is no disclosure of any specific starting material or of any of the conditions under which a process is to be carried out, undue experimentation is required; there is a failure to meet the enablement requirements that cannot be rectified by asserting that all of the disclosure related to the process is within the skill of the art","[i]t is the specification, not the knowledge of one skilled in the art, that must supply the novel aspects of an invention in order to constitute adequate enablement". The instant specification is not enabling for the full scope of the claimed invention because one cannot follow the guidance presented therein and practice the claimed method without first making a substantial inventive contribution.
Given that the nature of the invention is a vaccine composition comprising any modification made to the RNA or peptide and a method of in vivo prevention and treatment of atherothrombosis, a person having ordinary skill in the art would have to perform multiple further experiments, in human clinical trials, or in animal models that are predictive of treatment, in order to demonstrate the invention could be used with a reasonable expectation of success. The amount of experimentation required for enabling guidance, commensurate in scope with what is claimed, goes beyond what is considered ‘routine' within the art, and constitutes undue further experimentation in order to make a vaccine composition comprising any modification to the RNA or peptide and to use the method with a reasonable expectation of successfully treating atherothrombosis.
Therefore, claims 3, 7, and 15-19 lack enablement.
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 1 and 5-6 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more. The claims recite the nature-based RNA/peptide products of exon 6 to exon 8 of Δ7sTNFR2 and exon 6 to exon 9 of Δ7,8 TNFR2, represented in SEQ ID NOs: 5-8, 10, and 12. MPEP 2106 sets forth the multistep process for determining subject matter eligibility.
Considering the flowchart of subject matter eligibility in MPEP § 2106, the claims are directed to a product, which is a statutory category of invention. (Step 1: YES).
These claims recite a composition comprising SEQ ID NOs: 5-8, 10, and 12, which are naturally occurring splice variants of TNFR2 (see abstract of Lainez et al., 2004) and therefore a product of nature (see MPEP § 2106.04b). Therefore, the claims recite at least one judicial exception (STEP 2A, Prong One: YES).
According to Step 2A, Prong Two, set forth in MPEP 2106.04, the claims are next evaluated with respect to whether the judicial exception is integrated into a practical application. This analysis turns to the additional steps/elements recited by the claims. The claims require the additional elements of a vaccine and one or more pharmaceutically acceptable excipients. The RNA/peptide sequences of sTNFR2 exons 6 to 9 and 6 to 8 do not naturally occur in one or more pharmaceutically acceptable excipients as a vaccine. (Step 2A, Prong Two: YES)
According to Step 2B, set forth in MPEP 2106.05, the claims are next evaluated as to whether any additional element, or combination of additional elements, in the claims are sufficient to ensure that the claim as a whole amounts to significantly more than the judicial exception. Kallen et al., 2016 (US20160168227A1) teaches the additional elements of a vaccine composition that includes one or more pharmaceutically acceptable excipients are well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality. Therefore, the additional elements amount to adding insignificant extra-solution activity to the judicial exception, as well as simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception and do not amount to significantly more. (STEP 2B: NO)
Therefore, claims 1 and 5-6 are rejected.
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 1 and 3-8 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Sazani et al. 2007 (US20070249538A1).
The instant claims are drawn to an RNA and peptide vaccine composition. The RNA vaccine comprises a sequence selected from one or more of SEQ ID NO: 5, 7, 9, 11, or 13–16. The peptide vaccine comprises a sequence selected from one or more of SEQ ID NO: 6, 8, 10, or 12. The sequences comprise the RNA or peptide sequences of sTNFR2 exons 6-9 and 6-8, where exons 7-8 and 7 were removed, respectively. For the RNA sequences, the claims recite that the nucleotide sequence comprises one or more modifications to the ribose sugar, the nucleotide base, the 5′-terminus, the 3′-terminus, or combinations thereof. For the peptide sequences, the claims recite that the polypeptide sequence comprises one or more modifications to the peptide backbone, the amino acid side chains, the N-terminus, the C-terminus, or combinations thereof. The vaccine composition further comprises one or more pharmaceutically acceptable excipients and is a nanoparticle formulation.
Sazani teaches sTNFR2 Exons 6/8 Δ7 RNA with SEQ ID NO: 9 (Db), which has 100% sequence identity to instant SEQ ID NO: 5 (Qy), as shown below.
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Sazani teaches sTNFR2 Exons Δ7 peptide with SEQ ID NO: 10 (Db), which has 100% sequence identity to instant SEQ ID NO: 6 & 10 (Qy), as shown below.
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Sazani teaches that these peptides and RNAs can be administered with pharmaceutically acceptable excipients to treat a human with an inflammatory disease or condition (claims 1, 8, 9, 11-13, 18-19, 21-23, & 25; para [0021, 0060, 0068-0072, & 0113). Further, Sazani teaches the peptides can contain a processing, chemical, or post-translational modification (claim 3; para [0067]). Sazani teaches that the mRNAs can be chemically modified by various means (para [0073-0076]) and can be operably linked to a regulatory sequence (claim 20; para [0054]). Sazani teaches that the peptide compositions can be systemically or locally administered, and can be administered by bolus injection, continuous infusion, sustained release from implants, or other suitable techniques to treat TNF-dependent inflammatory diseases (para [0113-0114]). Sazani teaches that it is particularly preferred for the mRNAs and peptides to be contained within a lipid nanoparticle composed of DOTAP (para [0084]). Sazani teaches that the peptide can be administered in therapeutically effective amounts preferably ranging from about 0.1 mg/kg/week to about 100 mg/kg/week (para [0114]).
Therefore, Sazani anticipates the structure required by instant claims 1 and 3-8.
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.
Claims 15-18 are rejected under 35 U.S.C. 103 as being unpatentable over Sazani et al. 2007 (US20070249538A1), as applied above to claims 1 and 3-8, in view of Curin-Serbec et al. 1997 (SI9600206A), Carlsson et al. 2018, Amirfakhryan 2020, and Kireev et al. 2022.
The instant claims are drawn to a method of using the vaccine composition recited above to treat atherothrombosis. The instant claims are drawn to a vaccine dose of 30 µg to 100 µg that is administered at the initial administration, at 4 weeks, at 10 weeks, and at 16 weeks.
The teachings of Sazani are recited above.
While Sazani teaches the structure required for instant claims 1 and 3-8, Sazani does not teach a method of using the composition as a vaccine to treat atherothrombosis. The deficiencies of Sazani are remedied by the teachings of Curin-Serbec, Carlsson, Amirfakhryan, and Kireev.
Curin-Serbec teaches a method of immunizing mice against sTNFR2 by first administering a composition comprising sTNFR2 peptides and complete Freund's adjuvant, followed by another dosage a month later (instead using Freund's incomplete adjuvant), followed by a third dosage a month later (instead using the excipient, saline) (Examples, Claims, Abstract), and subsequent isolation of anti-sTNFR2 antibodies (Example 5). Curin-Serbec teaches that these anti-sTNFR2 antibodies can be used to treat disease states where the amount of TNF-alpha is increased, such as autoimmune diseases and inflammation (The state of the art, 2nd para; claims). Curin-Serbec teaches that researchers originally planned to use increased levels of TNF-alpha to treat cancer until subsequent studies showed that increasing TNF-alpha would have negative effects and is actually associated with the development of various diseases including chronic inflammation and autoimmune diseases (The state of the art, 2nd para). Curin-Serbec teaches that this led to the goal of developing therapeutic products that neutralized the action of TNF-alpha (the state of the art, 3rd para).
While Curin-Serbec teaches that neutralizing the action of TNF-alpha by inducing an immune response to sTNFR2 can be used to treat autoimmune diseases and inflammation, Curin-Serbec is silent as to whether the antibodies produced endogenously could potentially treat atherothrombosis within the vaccinated host. These deficiencies of Curin-Serbec are remedied by the teachings of Carlsson and Amirfakhryan.
Carlsson remedies a deficiency by directly implicating increased levels of sTNFR2 in atherothrombosis. Carlsson teaches that sTNFR2 is involved in several mechanisms underpinning plaque rupture, the primary events leading to most myocardial infarctions, such as stress response cascades and inflammation (introduction, 1st para). Carlsson teaches that elevated levels of sTNFR2 are associated with increased risk of myocardial infarction (Abstract; Discussion). Carlsson teaches that the association of elevated levels of sTNFR2 and increased risk of myocardial infarction could be explained by direct atherosclerotic effects, as both receptors are markers of a higher systemic inflammatory states, and that the initiation of formation of atherosclerotic lesions is in part an inflammatory process, as well as the two main causes of atherothrombosis, and the final trigger of most thrombotic and atherosclerotic events is plaque rupture and endothelial erosion (Discussion, 4.3. Possible mechanisms for the observed associations, 1st para). Carlson teaches that anti-TNF therapies are potent in lowering systemic inflammation, have not been associated with increased cardiovascular risk, improve left ventricular structure in patients with heart failure, and suggests treating patients with high levels of sTNFR2 with anti-TNF therapies to prevent myocardial infarctions (4.4. Clinical implications).
While Carlsson implicates sTNFR2 in atherothrombosis and suggests anti-TNF therapies, Carlson does not explicitly suggest vaccination against sTNFR2 to treat atherothrombosis. Amirfakhryan remedies this deficiency.
Amirfakhryan teaches that many trials have been conducted on vaccination for atherosclerosis, including vaccines against TNF-α to produce neutralizing antibodies against TNF-α (Role of Immune System in Atherosclerosis, Vaccination; Table 1-2). Amirfakhryan teaches that vaccination against atherosclerosis is both a promising strategy to overcome the disorder and that “There is an increasing necessity for developing an effective, economical, long-lasting, accessible, and convenient vaccination method (abstract),” that vaccination against atherosclerosis is complex and challenging and still in its infancy, and there is still a need to identify proper atherogenesis-related antigens (Background, last para).
Importantly and contradictorily from the teachings of Curin-Serbec and Carlsson, Sazani teaches away from using the mRNA and peptides as vaccines, instead teaching that the mRNAs and peptides can be used to increase levels of sTNFR2 to provide therapeutic effect (para[0013-0016]). As the 2007 disclosure of Sazani seems to contradict with the 1997 disclosure of Curin-Serbec and the 2007 disclosure of Carlsson (with one wanting to increase sTNFR2 levels to provide an anti-TNF-alpha therapeutic effect and the others wanting to target sTNFR2 to provide an anti-TNF-alpha therapeutic effect), an ordinary artisan would look to more recent prior art to elucidate this contradiction over the mechanism of action. The April 2022 disclosure by Kireev remedies this contradiction.
Kireev teaches that “Soluble receptors can compete with membrane-bound receptors for TNF binding and consequently inhibit TNF bioactivity; however, the functional interactions between TNF and its soluble receptors are complex. The addition of sTNFR1 and sTNFR2 to trimeric TNF leads to the formation of complexes between them, stabilizing the active TNF form. TNF can dissociate from this complex and replace decayed TNF at the periphery, thus maintaining a constant concentration of unbound bioactive trimeric cytokine...Factors sTNFR1 and sTNFR2 can act as TNF antagonists, TNF-carrier proteins, slow-release reservoirs for TNF, stabilizers of TNF bioactivity capable of increasing the cytokine half-life, and a TNF buffer by inhibiting the effect of high TNF concentrations and providing the effect of low and well-controlled cytokine levels on cells. Thus, soluble TNF receptors affect local and systemic TNF bioavailability” (Discussion, 2nd para). In view of Kireev’s teaching it is now clear that reducing the levels of sTNFR2 through vaccination could be a potential approach to treating atherothrombosis by teaching the immune system to target and destroy both the free sTNFR2 and the complexed sTNFR2 to reduce both the half-life of circulating TNF-alpha and remove the slow-releasing reservoirs of TNF-alpha.
It would have been prima facie obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to arrive at the claimed invention from the disclosure of Sazani, Curin-Serbec, Carlsson, Amirfakhryan, and Kireev. One with ordinary skill in the art would be motivated to make and use the claimed invention because an ordinary artisan would find it obvious in view of Kireev and Carlson that the method of Curin-Serbec using the peptide of instant SEQ ID NO: 10 taught by Sazani could potentially treat atherothrombosis. Further, one with ordinary skill in the art would be motivated to make and use the claimed invention because an ordinary artisan would find it obvious in view of Amirfakhryan that endogenously produced antibodies against sTNFR2 (which were induced through immunization against sTNFR2 as taught by Curin-Serbec) could potentially treat atherothrombosis within the host, making it clear that sTNFR2 is a potential atherogenesis-related antigen that could be used in a human vaccination protocol. While it is obvious in view of these disclosures to attempt to treat atherothrombosis through vaccination against sTNFR2, it is also clear from the disclosure of Amirfakhryan that the mere theory of the vaccine is not sufficient to prove the vaccine can treat atherothrombosis and requires evidence to show that the claimed invention is capable of treating atherothrombosis (see 112a enablement rejection above).
The prior art only differs from the claimed invention recited in instant claims 16-18 with respect to the claimed administration regimen. The Court has stated that generally such differences amount to mere optimization and will not support patentability unless there is evidence indicating the claimed feature is critical. It would have been prima facie obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to arrive at the claimed invention because an ordinary artisan would have found it obvious to optimize the administration regimen through routine experimentation. An ordinary artisan would have been motivated to optimize the administration regimen to make the most effective regimen. MPEP 2144 sets forth Applicant’s burden for rebuttal of a prima facie case of obviousness based upon routine optimization. Applicant must provide either a showing that the particular amount or range recited within the claims is critical; and/or a showing that the prior art reference teaches away from the claimed amount. In the instant case, the specification as filed provides no evidence that the particular amount or range recited within the claims is critical.
Claims 9-14 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Sazani et al. 2007 (US20070249538A1), Curin-Serbec et al. 1997 (SI9600206A), Carlsson et al. 2018, Amirfakhryan 2020, and Kireev et al. 2022, as applied above to claims 15-18, in view of Kinsella et al. 2016 (US20160016900A1).
The instant claims are drawn to a vascular stent, leaflets of a heart valve, and a drug eluting balloon comprising the vaccine recited above, where the vaccine is immediately released or controlled released. The instant claims are also drawn to a method of treating atherothrombosis by administering the vaccine directly to atherosclerotic plaques using microcatheters.
The teachings of Sazani, Curin-Serbec, Carlsson, Amirfakhryan, and Kireev are recited above.
Neither Sazani, Curin-Serbec, Carlsson, Amirfakhryan, or Kireev explicitly teach a vascular stent, leaflets of a heart valve, and a drug eluting balloon comprising the vaccine recited above, where the vaccine is immediately released or controlled released. They also do not explicitly teach a method of treating atherothrombosis by administering the vaccine directly to atherosclerotic plaques using microcatheters.
Kinsella teaches a method for treating atherothrombosis (claim 13; para [0008-0009 & 0029]) comprising administering an effective dose of an antithrombotic compound (abstract; claim 12) and one or more pharmaceutically acceptable excipients (para [0143, 0146, & 0151]) with or without being coated onto, and used in conjunction with, an implanted drug eluting stent, drug eluting balloon, bifurcation stent, by-pass graft vessel stent, or aortic or mitral valves used in trans-catheter aortic valve intervention (a microcatheter) (para [0030-0031, 0032-0033, 0141, 0153-0154, & 0157]).
It would have been prima facie obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to arrive at the claimed invention from the prior art disclosures. In further pursuit of making and using the vaccine, one of ordinary skill in the art would look to potential methods of delivering the treatment to a patient. This is where Kinsella remedies this deficiency. One with ordinary skill in the art would be motivated to make and use the claimed invention because Sazani teaches the peptide of instant SEQ ID NO: 10 can be applied to implants and Kinsella teaches many advantageous embodiments of how to administer the vaccine via from which an ordinary artisan could pick and choose in the attempt to make the most effective treatment. The person of ordinary skill in the art would have had a reasonable expectation of success based on the disclosures of these prior art references of delivering the vaccine composition via a vascular stent, leaflets of a heart valve, a drug eluting balloon, or microcatheter, where the vaccine is immediately released or controlled released. To reiterate as to whether the composition can treat atherothrombosis, it is clear from the disclosure of Amirfakhryan that the mere theory of the vaccine is not sufficient to prove the vaccine can treat atherothrombosis and requires evidence to show that the claimed invention is capable of treating atherothrombosis (see 112a enablement rejection above). Therefore, claims 9-14 and 19 are obvious.
Prior Art
None of the prior art references above teach the 5’ UTR and 3’ UTR specified in instant SEQ ID NOs: 13 and 14, respectively. Nor do they teach using instant SEQ ID NOs: 9 and 13-14 within the construct of the RNA vaccine specified by instant SEQ ID NOs: 15.
Yanagi teaches a 5’UTR (Db) with 89.6% sequence identity to Instant SEQ ID NO: 13 (Qy), as shown below.
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Trinklein teaches a 3’UTR with SEQ ID NO: 3040 (Db) which has 97% sequence identity to Instant SEQ ID NO: 14 (Qy), as shown below.
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Therefore, it would not be obvious to the ordinary artisan from the prior art disclosures to construct the specific sequences identified in instant SEQ ID NOs: 15 (which comprises SEQ ID NO: 13 + ATG [start codon] + SEQ ID NO: 9 + TAA [stop codon] + SEQ ID NO: 14) as vaccines, nor administered the vaccine via vascular stent, leaflets of a heart valve, drug eluting balloon, or microcatheter. While instant claim 2 is rejected due to dependency on instant claim 1, instant SEQ ID NO: 15 is free of the prior art.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of co-pending Application No. 18/813220. Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are recited above.
The co-pending claims recite a vaccine for immunizing a subject from an inflammatory condition or treating an inflammatory condition, wherein the vaccine comprises an mRNA vaccine encoding Δ7 or Δ7,8 splice variants of soluble TNF receptor II (sTNFR2) or a peptide vaccine comprising the amino acid sequence of Δ7 or Δ7,8 splice variants of sTNFR2 (claim 1). The dependent claims recite identical sequences to instant SEQ IDs, that the vaccine’s nucleic acids and/or peptide backbone can be modified, that the vaccine can be immediately or controlled released, that it can be used to treat mammals, and that the vaccine can treat atherothrombosis.
Independent instant claims 1, 5, 9, 11, 13, 15, and 19 are encompassed by the independent co-pending claim 1 because co-pending claim 1 encompasses any vaccine comprising an mRNA vaccine encoding Δ7 or Δ7,8 splice variants of soluble TNF receptor II (sTNFR2) or a peptide vaccine comprising the amino acid sequence of Δ7 or Δ7,8 splice variants of sTNFR2 and the independent instant claims require a vaccine comprising an RNA vaccine encoding sequence-specific Δ7 or Δ7,8 splice variants of soluble TNF receptor II (sTNFR2) or a peptide vaccine comprising specific amino acid sequences of Δ7 or Δ7,8 splice variants of sTNFR2.
Instant SEQ ID NOs: 6 and 10 have 100% identical sequence identity to co-pending SEQ ID NO: 18. Co-pending SEQ ID NO: 20 has 100% identical sequence identity to instant SEQ ID NOs: 8 and 12. Instant SEQ ID NO: 9 has 100% identical sequence identity to co-pending SEQ ID NO: 17. Co-pending SEQ ID NO: 17 has 100% identical sequence identity to instant SEQ ID NO: 15. Co-pending SEQ ID NO: 19 has 100% identical sequence identity to instant SEQ ID NOs: 11 and 16. Therefore, instant claims 1-2, 5-6, 9, 11, 13, 15 and 19 are encompassed and/or anticipated by co-pending claims 1-3, 6-7, as both the instant and co-pending claims require the same sequences.
Dependent instant claims 3 and 7 encompass the dependent co-pending claims 4, 5, and 8 because the instant claims 3 and 7 encompass any modification made to the RNA/peptide and the co-pending claims recite both generic and specific modifications made to the RNA/peptide. Dependent instant claims 10, 12, and 14 are encompassed by the dependent co-pending claim 9 because the co-pending claim encompasses any vaccine of co-pending claim 1 that’s immediately released or controlled released and the instant claims require a more specific version of the vaccine that’s immediately released or controlled release.
Therefore, claims 1-19 are rejected as being unpatentable over co-pending Application No. 18/813220. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Advisory Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH CESARE whose telephone number is (571)272-6908. The examiner can normally be reached Monday - Friday 10am-4pm.
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/JOSEPH D. CESARE/ Examiner, Art Unit 1675 /JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675
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