Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Priority
Acknowledgement is made of Applicant’s claimed domestic priority under 35 U.S.C. § 119(e), of U.S. Provisional Application Serial No. 63/174,287, filed 04/13/2021.
Status of the Claims
The amendment dated 06/04/2024 is acknowledged. Claims 1-18,23-26,30-32 and 36 are pending and under examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 01/17/2024, 06/04/2024 and 07/22/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement(s) is/are being considered by the Examiner.
Drawings
The drawing filed on 10/12/2023 are acknowledged and accepted by the Examiner.
Claim Rejections - 35 USC § 112
The following is a quotation 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.
Claims 1-18, 23-26, 30-32 and 36 rejected under 35 U.S.C. 112(a), because the specification, while being enabling for while being enabling for reciting an “immunogenic composition” comprising a lipid nanoparticle that comprises: (a) a messenger ribonucleic acid (mRNA) comprising an open reading frame encoding an Epstein-Barr virus (EBV) glycoprotein 220 (gp220); (b) an mRNA comprising an open reading frame encoding glycoprotein 42 (gp42); (c) an mRNA comprising an open reading frame encoding glycoprotein L (gL); and (d) an mRNA comprising an open reading frame encoding glycoprotein H (gH), does not reasonably provide enablement for reciting a “vaccine”. 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. Enablement is considered in view of the Wands factors (MPEP 2164.01(a)).
"The test of enablement is not whether any experimentation is necessary, but whether,
if experimentation is necessary, it is undue." In re Angstadt, 537 F.2d 498, 504, 190 USPQ 214,
219 (CCPA 1976). Factors to be considered in determining whether undue experimentation is
required are summarized in In re Wands (858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir.
1988)) as follows: (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. See MPEP § 2164.0l(a). The Factors considered to be most relevant to the
instant rejection are addressed in detail below.
Breadth of the claims. The claims are directed to a vaccine comprising a lipid nanoparticle that comprises: (a) a messenger ribonucleic acid (mRNA) comprising an open reading frame encoding an Epstein-Barr virus (EBV) glycoprotein 220 (gp220); (b) an mRNA comprising an open reading frame encoding glycoprotein 42 (gp42); (c) an mRNA comprising an open reading frame encoding glycoprotein L (gL); and (d) an mRNA comprising an open reading frame encoding glycoprotein H (gH).
Nature of the invention. The invention relates to Epstein-Barr virus mRNA vaccines for the treatment or prevention of EBV infections, whereby the mRNA undergoes intracellular ribosomal translation to endogenously express the viral proteins encoded by the vaccine comprising synthetic viral mRNA to induce targeted immune responses against infectious pathogens such as EBV.
State of the prior art. Citing Cai et al. (Prophylactic and Therapeutic EBV Vaccines: Major Scientific Obstacles, Historical Progress, and Future Direction, Vaccines, 2021, 9:1-230, discloses “EBV mRNA vaccine development is still in its early stages” and “vaccines have been used to prevent and treat various diseases, and widespread vaccination has saved millions of lives by successfully eradicating smallpox and significantly reducing other infectious diseases. Traditional vaccine formulations, such as subunit vaccines, attenuated live vaccines, and inactivated pathogens vaccines, that provide strong protection against many deadly diseases, are unsuitable for EBV. The low levels of neutralizing antibody titers elicited by gp350 subunit vaccines are insufficient to induce adequate immune protection. Future vaccines must adopt multipronged approaches capable of stimulating more than one arm of the immune system. Reasonable approaches involve improving adjuvants, protein–polymer formations, enhancing antibody diversity, or developing novel strategies, such as targeted B cell precursors that produce broadly neutralizing antibodies, novel viral vectors, and multi-vector sequential vaccines” and “The complexity of the EBV life cycle, the lack of suitable animal models, and our limited understanding of the immune response needed to prevent EBV infection have hindered the progress in vaccine development. There is still reason for cautious optimism that the numerous current clinical or preclinical developments for vaccine candidates will lead to further success, although this success may be modest and iterative” (page 14).
Working examples. The Applicant provides in vivo studies in Balb/c mice and Sprague Dawley rats to evaluate immunogenic compositions comprising mRNA encoding soluble EBV gp42 in combination with other EBV antigens (Tables 1 and 2). Applicant’s results show neutralizing antibody titers produced against B cell infection while not dampening neutralizing antibody titers produced against epithelial cell infection and the addition of mRNA encoding EBV gB was found to cause a drop in neutralizing antibody titers produced against B cell infection when added to vaccines comprising individual mRNAs encoding EBV gH, EBV gL, EBV gp220, and soluble EBV gp42) (Example 1-3). Applicant’s demonstrate antibodies raised by mRNA immunization were able to inhibit B cell and epithelial cell infection (Fig. 4), whereby the overall dose-dependent effect was modest: less than 2-fold for gp220 and gp42, and 2.3-fold for gHgL
Guidance in the specification. The Applicant’s disclosure indicates the mRNA vaccine against EBV as provide herein contains at least four mRNAs that encode viral proteins (gp220, gp42, gH and gL) in EBV. In some embodiments, these viral proteins are expressed in their native membrane-bound form for recognition by the immune system. In other embodiments, gp42 is expressed in a soluble form. In some embodiments, the vaccine further comprises an mRNA that encodes EBV glycoprotein B (gB). The EB V mRN A vaccines described herein are superior to current vaccines in several ways. For example, the lipid nanoparticle (LNP) delivery system used herein increases the efficacy of mRNA vaccines in comparison to other formulations, including a protamine-based approach described in the literature. The use of this LNP delivery system enables the effective delivery of chemically-modified RNA vaccines or unmodified mRNA vaccines, without requiring additional adjuvant to produce a therapeutic result (e.g., production neutralizing antibody titer).
Predictability or unpredictability of the art. While the relative skill of those in the art is high in using molecular techniques in making immunogenic compositions, the art broadly teaches the unpredictability of vaccine development (see, for example Oyston and Robinson, Journal of Medical Microbiology, 2012, 61:889-894). Oyston and Robinson outline several factors in the challenges of developing vaccines such as a) antigenic variation requires constant updating of vaccine formulations, b) gaining a greater understanding of the mechanisms of action of currently used adjuvants; development of vaccine delivery systems specifically for use in immunocompromised populations, c) high costs of vaccine development result in premature abandonment of potentially useful products (see Table 1 of Oyston and Robinson). While protection in mice has been shown to prevent death, there remains a low level of predictability about what will happen in human subjects, as discussed above. Particularly, evidence indicates, citing Goldman (Stanford Medicine, Cardiology, December 2025), “Elevated inflammatory cytokine signaling could be a class effect of mRNA vaccines. Notably, IFN-gamma signaling is a fundamental defense mechanism against foreign DNA and RNA molecules, including viral nucleic acids” and “IFN-gamma secreted in large amounts, however lofty its purpose, can trigger myocarditis-like symptoms and degradation of structural heart muscle proteins. That risk probably extends beyond mRNA-based COVID-19 vaccines” (article, last four para). Moreover, Chen et al. (Annual Review of Biomedical Engineering Current Developments and Challenges of mRNA Vaccines, 2022, 24:85-109), discloses “Adjuvants are necessary in traditional vaccines; however, the role of adjuvant effects in mRNA vaccines in generating adaptive immunity is still debated. Both mRNA and delivery systems can alter the adjuvant property of mRNA vaccines, making the use of these vaccines a challenge for future applications (Figure 2). In vivo transcription (IVT) mRNAs can be recognized by multiple PRRs, including retinoic acid–inducible gene I-like receptors, oligoadenylate synthetase receptors, and RNA-dependent protein kinase, and show inherent adjuvant properties. Such adjuvant effects are a double-edged sword that can be either beneficial in activating APCs for the generation of adaptive immunity or detrimental due to blocking mRNA translation; and “Apart from the adjuvant effect of mRNA, the delivery systems also have an adjuvant effect due to their inherent properties or co-encapsulation of other immune agonists. As mentioned above, two different STING agonists were explored to enhance the therapeutic outcome of cancer vac cines. Notably, the STING-activable LNP A18 also showed the strongest expression of mRNA at both local sites and draining lymph nodes, suggesting the coexistence of a high adjuvant effect and efficient antigen expression. Recent research reported the highly inflammatory effect of some preclinical LNPs. Intradermal injection of these blank LNPs induced massive neutrophil infiltration and production of various inflammatory cytokines and chemokines, e.g., IL-1β, IL-6, CCL3, and CCL4. The potent adjuvant activity might also contribute to the induction of adaptive immune responses by mRNA vaccines. However, stimulation by LNPs should be more carefully considered due to the potential toxicity and inflammation. Therefore, it is a great challenge to balance efficient antigen production, sufficient adjuvant effects, and side effects of current mRNA vaccines. To achieve such balance, more efforts should be spent on the investigation of the interaction among LNPs, mRNA, and the innate immune system” (page 98-99). Chen further states “Infectious pathogens may establish different levels of mutation rates during transmission, especially with RNA viruses. Moderna provided a clinical update on the neutralizing activity of mRNA-1273 on 16 emerging variants. The results showed decreased neutralization titers ranging from 2.1 to 8-fold reductions compared with D614G. Therefore, new strategies should be applied to overcome the rapid mutation of the virus” (page 101, fifth para).
Accordingly, when all the aforementioned factors are considered in toto, it would require undue experimentation to practice the claimed methods and having the claimed functions (i.e., a vaccine) in the invention. Thus, while the claims are enabled for an immunogenic composition against EBV in the specification, because the claims are broadly drawn to a vaccine they are rejected as exceeding the scope for which an enabling disclosure has been provided.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 1-4, 11-16, 23-25, 30-32 and 36 are rejected under 35 U.S.C. 103(a) as being unpatentable over Ciaramella et al. “Ciaramella” (WO2019/103993, IDS of record dated 01/17/2024) in view of Nabel et al. “Nabel” (WO2019/195314, IDS of record dated 01/17/2024).
The claims are directed to a vaccine, comprising a lipid nanoparticle that comprises:
(a) a messenger ribonucleic acid (mRNA) comprising an open reading frame encoding an
Epstein-Barr virus (EBV) glycoprotein 220 (gp220);
(b) an mRNA comprising an open reading frame encoding glycoprotein 42 (gp42);
(c) an mRNA comprising an open reading frame encoding glycoprotein L (gL); and
(d) an mRNA comprising an open reading frame encoding glycoprotein H (gH).
Regarding claims 1, 15, 23-25, 30-32 and 36, Ciaramella discloses compositions and methods of treatment comprising Epstein Barr Virus (EBV) mRNA vaccines formulated in lipid nanoparticles. The lipid nanoparticles comprise 20-60% ionizable cationic lipid, 5-25% non-cationic lipid, 25-55% sterol and 0.5-15% PEG-modified lipid (Compound 1 lipids, instant claims 31 and 32). Balb/c mice were vaccinated intramuscularly with EBV vaccines comprising mRNA encoding EBV gH (SEQ ID NO: 38, which comprises mRNA gH SEQ ID NO: 6, 100% identity, gL (SEQ ID NO: 36, which comprises mRNA gL SEQ ID NO: 8, 100% identity), gp42 (SEQ ID NO: 34, which comprises mRNA gp42 SEQ ID NO: 14, 100% identity, and 91.9% identity to SEQ ID NO: 10) and gp350 (SEQ ID NO: 28)(instant claims 1-2, 15, 23-25). A 2μg dose was administered on day 1 and then again on day 29. Mice were bled on day 28 and day 57. Results demonstrated that the EBV vaccine induced neutralizing antibody titers at day 28 (4 weeks post prime) and day 57 (4 weeks post boost) following vaccination. The vaccine may also comprise mRNA encoding EBV gB, or mRNA comptising a poly A tail, cap and/or a 1-methylpseudouridine modification (page 49, lines 30-33, page 71, lines 2-6, Examples 1-12, Figure 5, SEQ ID NO: 209, pages 71-181) (instant claims 30 and 36).
Ciaramella does not explicitly disclose an mRNA ORF encoding EBV gp220.
Nabel, however, discloses antigenic EBV polypeptides and their use in eliciting antibodies against EBV. Immune responses elicited by a monovalent (gH/gL/gp42 nanoparticle (NP) + naked ferritin NP) or bivalent (gH/gL/gp42 NP+ gp220 NP) composition were assessed. Balb/c mice were immunized with a 3-week interval between doses. 100μL of the NP composition containing 1μg of each NP was administered with an AF03 adjuvant. No interference was seen due to administration of the NP in bivalent formulation, as compared to administration of the monovalent form (Abstract, [00123]- [00127], [00276], Examples [00282]- [00317]).
Accordingly, it would have been obvious to one of ordinary skill in the art to generate an immunogenic composition comprising a lipid nanoparticle that comprises mRNAs comprising open reading frames encoding gp42, gL and gH as disclosed by Ciaramella, whereby combining an additional mRNA encoding gp220 would be combined as taught by Nabel such that gp350/220 is a major outer envelope glycoprotein complex and EBV multivalent vaccines comprising gp220 are known to the person skilled in the art. The courts have said: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose . . . . [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.) See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious). (See MPEP §2144.06(I) – Combining Equivalents Known For The Same Purpose). One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success to combine the mRNAs into a multivalent vaccine given the fact that Nabel has demonstrated the improved efficacy (i.e. increased neutralizing antibody titers) of bivalent immunogenic compositions comprising gp220 (Examples [00282]- [00317]). Therefore, the claimed invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Regarding claims 3-4, 11-12, 13-14, 16, the amount of each mRNA (instant claims 3-4, 13-14); mass ratio (instant claims 11-12 and 16), it is not inventive and considered routine and obvious to one of ordinary skill in the art as routine optimization. According to section 2144.05 of the M.P.E.P., "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Application of Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980). It would have been obvious for one of ordinary skill to determine the appropriate percentage/parts by weight of the mRNA components in the composition of the methods disclosed by the prior art by routine experimentation procedures known in the art. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success in order to achieve the maximum (production or activity or therapeutic) response from the composition. Therefore, the claimed invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
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 Langi, 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
on line using web-screens. An eTerminal Disclaimer that meets all requirements is autoprocessed
and approved immediately upon submission. For more information about eTerminal
Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-4, 11-14, 16, 30-31 and 36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 50-51, 54-55 and 58 of co-pending Application No. 19/084,092. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The co-pending claims are directed to:
50. An Epstein-Barr virus (EBV) vaccine comprising a lipid nanoparticle, a first
mRNA, and a second mRNA, wherein the first mRNA comprises a first open reading frame
(ORF) encoding an EBV glycoprotein L (gL) protein consisting of the amino acid sequence set
forth in SEQ ID NO:36 (SEQ ID NO: 8 of instant application), and wherein the second mRNA comprises a second ORF encoding an EBV glycoprotein H (gH) protein consisting of the amino acid sequence set forth in SEQ ID NO:38 (SEQ ID NO: 6 of instant application) (instant claims 1-2).
51. The EBV vaccine of claim 50, further comprising a third mRNA, wherein the
third mRNA comprises a third ORF encoding an EBV glycoprotein 42 (gp42) protein (instant claims 1-2). With respect to instant claims 3-4, 11-14 and 16, the amount of each mRNA (instant claims 3-4, 13-14); mass ratio (instant claims 11-12 and 16), it is not inventive and considered routine and obvious to one of ordinary skill in the art as routine optimization. According to section 2144.05 of the M.P.E.P., "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Application of Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980). It would have been obvious for one of ordinary skill to determine the appropriate percentage/parts by weight of the mRNA components in the composition of the methods disclosed by the prior art by routine experimentation procedures known in the art. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success in order to achieve the maximum (production or activity or therapeutic) response from the composition.
54. The EBV vaccine of claim 50, wherein the lipid nanoparticle comprises an
ionizable cationic lipid, a neutral lipid, a sterol, and a polyethylene glycol (PEG)-modified lipid (instant claims 30-31).
55. The EBV vaccine of claim 51, wherein the lipid nanoparticle comprises an
ionizable cationic lipid, a neutral lipid, a sterol, and a PEG-modified lipid (instant claims 30-31).
58. A method of EBV vaccination comprising administering to a human subject
the EBV vaccine of claim 50 in an amount effective to induce in the human subject an EBV
neutralizing antibody titer and/or a T cell immune response (instant claim 36).
There is no patentable difference between the claimed composition/method and the co-pending composition/method in that the U.S. Application No. 19/084,092 discloses An Epstein-Barr virus (EBV) vaccine comprising a lipid nanoparticle, a first mRNA, and a second mRNA, wherein the first mRNA comprises a first open reading frame (ORF) encoding an EBV glycoprotein L (gL) protein consisting of the amino acid sequence set forth in SEQ ID NO:36 (SEQ ID NO: 8 of instant application), and wherein the second mRNA comprises a second ORF encoding an EBV glycoprotein H (gH) protein consisting of the amino acid sequence set forth in SEQ ID NO:38 (SEQ ID NO: 6 of instant application), whereby application no. 18/286,705 anticipates 19/084,092. Moreover, The MPEP states “where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977).
Claims 23-26 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 50 and 51 of co-pending Application No. 19/084,092 in view of Ciaramella et al. “Ciaramella” (WO2019/103993, IDS of record dated 01/17/2024) as applied to claims 1-2 above. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The instant claims are directed to (23) The vaccine of claim 1, wherein the gp42 comprises an amino acid sequence having at least 85%, at least 90%, at least 95%, or at least 98% identity to the amino acid sequence of SEQ ID NO: 14; (24) The vaccine of claim 23, wherein the gp42 comprises the amino acid sequence of SEQ ID NO: 14; (25) The vaccine of claim 2, wherein the soluble
gp42 comprises an amino acid sequence having at least 85%, at least 90%, at least 95%, or at least
98% identity to the amino acid sequence of SEQ ID NO: 10; and (26) The vaccine of claim 25, wherein the soluble gp42 comprises the amino acid sequence of SEQ ID NO: 10.
The conflicting clams differ from instant claims 23-26 in that it does not recite the amino acid sequence, SEQ ID NOs. 10 and 14, but the genus of mRNAs encoding gp42.
Ciaramella discloses compositions and methods of treatment comprising Epstein Barr Virus (EBV) mRNA vaccines formulated in lipid nanoparticles. Balb/c mice were vaccinated intramuscularly with EBV vaccines comprising mRNA encoding EBV gH (SEQ ID NO: 38, which comprises mRNA gH SEQ ID NO: 6 of instant application, 100% identity, gL (SEQ ID NO: 36, which comprises mRNA gL SEQ ID NO: 8 of instant application, 100% identity), gp42 (SEQ ID NO: 34, which comprises mRNA gp42 SEQ ID NO: 14 of instant application, 100% identity, and 91.9% identity to SEQ ID NO: 10). It would have been obvious to one of ordinary skill in the art to generate an immunogenic composition comprising a lipid nanoparticle that comprises mRNAs comprising open reading frames encoding gp42, gL and gH as disclosed by Ciaramella. One of ordinary skill in the art would have been motivated to use a known mRNA encoding the gp42 amino acid as taught by Ciaramella with a reasonable expectation of success given the knowledge that the mRNA comprising an open reading frame encoding gp42 is well-known in the art and for the benefit of having an effective composition for the production, activity and/or therapeutic response from the composition.
Claim 32 is provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claim 54 of co-pending Application No. 19/084,092 in view of Ciaramella et al. “Ciaramella” (WO2019/103993, IDS of record dated 01/17/2024) as applied to claim 1 above. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The instant claim is directed to the vaccine of claim 1 wherein the ionizable amino lipid is Compound I.
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The conflicting clams differ from instant claim 32 in that it does not recite compound 1 but the genus of an ionizable cation lipid.
Ciaramella discloses compositions and methods of treatment comprising Epstein Barr Virus (EBV) mRNA vaccines formulated in lipid nanoparticles. The lipid nanoparticles comprise 20-60% ionizable cationic lipid, 5-25% non-cationic lipid, 25-55% sterol and 0.5-15% PEG-modified lipid (Compound 1 lipid, instant claim 32). The ionizable amino lipid disclosed by Ciaramella appears to be a standardized lipid utilized by ModernaTX, INC (Applicant of inventor Ciaramella, WO2019/103993). It would have been obvious to one of ordinary skill in the art to generate an immunogenic composition comprising a lipid nanoparticle that comprises an ionizable amino lipid comprising compound I as disclosed by Ciaramella. One of ordinary skill in the art would have been motivated to use a known lipid compound as taught by Ciaramella (ModernaTX) with a reasonable expectation of success given the knowledge that the compound is well-known in the art for the benefit of having a stable, effective composition for the production, activity and/or therapeutic response from the composition.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Barry Chestnut whose telephone number is (571)270-3546. The examiner can normally be reached on M-Th 8:00 to 4:00.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas Visone can be reached on 571-270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BARRY A CHESTNUT/Primary Examiner, Art Unit 1672