DETAILED ACTION
Claims 1-17, 19 and 27-31 are under current consideration.
Please note the examiner has changed.
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Claim Rejections - 35 USC § 112
Claim Rejections - 35 USC § 112, para. 1, WD
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-17, 19, 27 and 29-31 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
Several of the claims are directed to functional limitations.
See claim 7 directed to the immune enhancing nanoemulsion which is capable of induing Th1, Th2 and/or Th17 immune responses.
See claim 13 directed to (in part): a method for inducing an enhanced immunity against diseases caused by HSV.
See claim 16 directed to (in part): a method for preparing a nanoemulsion HSV vaccine useful for the treatment or prevention of an HSV infection in humans.
The specification does not provide any correlation between the genus of vaccine compositions as so broadly claimed to the functional properties of the claims. The specification provides a “Formulation 1” and a “Formulation 2” on p. 44-45, wherein the amount of each component is provided. Note that Formulation 2 comprises one additional component, poloxamer 188, compared to Formulation 1. See p. 39 for Table 1 which provides that the W805EC formulation is Formulation 1, comprising specific amounts water, soybean oil, ethanol, polysorbate 80 and CPC. There is no teaching of what components or amounts are required for the “immune enhancing nanoemulsion”.
See Bielinska (2010-cited by the IDS). See p. 2 for “II. Materials and Methods” for describing the ingredients of the NE, or the W805EC formulation, as comprising specific amounts of soybean oil, cetyl pyridinium chloride, polysorbate, ethanol and water. The author describes the droplets of the formulation to have a diameter of 350 nm and teaches the formulation produces Th1 and Th17 immunity.
See attached reference by Wilson (Particuology, 2022) which provides that the selection of the surfactant is critical for forming and stabilizing nanoemulsions, and the choice of oils and surfactants need to be biocompatible with no toxic effects; see p. 86. See p. 92, col. 1 for teaching the following: Selection of an appropriate emulsion excipient requires careful consideration of the specific needs of a nanomedicine formulation. The excipient must readily solubilize the drug of concern, be non-toxic, biocompatible and form monodisperse stable emulsion droplets to meet FDA guidelines. The most common excipients for pharmaceutical use are sourced from plant-based oils, containing long chain and/or medium chain triglycerides, as they require little assistance to solubilize drugs, have good biocompatibility and can be easily purified to remove toxic trace compounds (Strickley, 2004). Similarly, pharmaceutical surfactants must be biocompatibility, have low toxicity and good surface activity. There are a variety of common FDA approved surfactants used to deliver compounds of pharmaceutical interest including lecithin phospholipid surfactants sourced from egg or plant sources and non-ionic small molecule surfactants such as Span, Brij and Tween surfactants (Tharwat, 2005).”
Note that the claimed nanoemulsion comprises polysorbate 80, polysorbate 20 or a combination thereof as a surfactant; see claim 27. However, it is not clear if the combination of tangerine oil or any other oil of claim 29 and the claimed surfactant would be biocompatible with no toxic effects, and if the combination would lead to droplets with a diameter of less than 1000 nm.
The claims are rejected for lacking adequate written description for the genus of nanoemulsions, leading to a genus of vaccine compositions, and their correlation of to the required functional properties of the claims.
Applicant argues that the claims have been amended to include specific amounts of components and that claim 29 is a list of pharmaceutically acceptable oils.
Applicant’s argument has been fully considered and not found persuasive.
The specification only teaches two specific formulations of “Formulation 1” and a “Formulation 2” on p. 44-45. The claims are drawn to broad % ranges. There is no teaching in the specification except the two formulations to show what percentages will work. There are no examples, there are no teaching of the range of pharmaceutical oil will function at the range of 1% to 80% or with all the oils listed to function as an oil-in-water nanoemulsion of the recited diameter to serve as a vaccine.
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 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 pre-AIA 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, 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 pre-AIA 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 pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1-17, 19, and 29-33 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Bielinska et al. (Crit Rev Immunol., 2010-cited by the IDS), Burke (US Patent 5747039-cited the IDS) and Baker (20090291095-see attached form 892).
The claims are directed to (in part): A vaccine composition comprising:(a) an immune enhancing nanoemulsion, wherein the nanoemulsion comprises an oil- in-water nanoemulsion or a dilution thereof, and (b) at least one herpes simplex virus (HSV) antigen, wherein the HSV antigen is whole HSV virus, an isolated HSV antigen, or a combination thereof, and wherein the HSV antigen is present within the nanoemulsion; see claim 1.
A method for inducing an enhanced immunity against diseases caused by herpes simplex viruses comprising the step of administering to an individual an effective amount of a nanoemulsion HSV vaccine composition comprising: (a) a nanoemulsion, wherein the nanoemulsion comprises an oil-in-water nanoemulsion or a dilution thereof, and (b) at least one herpes simplex virus (HSV) antigen, wherein the HSV antigen is whole HSV virus, an isolated HSV antigen, or a combination thereof, and wherein the at least one HSV antigen is present within the nanoemulsion; see claim 13.
A method for preparing a nanoemulsion HSV vaccine useful for the treatment or prevention of an HSV infection in humans comprising:(a) synthesizing in a eukaryotic host one or more full length or immunogenic fragment HSV surface antigens utilizing recombinant DNA genetics vectors and constructs, wherein the HSV surface antigen is selected from the group consisting of HSV gB, HSV gC, HSV gD, and HSV gE; (b) isolating the one or more surface antigens or immunogenic fragments thereof from the eukaryotic host; and (c) formulating the one or more surface antigens with an oil-in-water nanoemulsion; see claim 16.
Bielinska is cited for teaching a mucosal nanoemulsion (NE) adjuvant which induces a Th17 response to diverse antigens; see abstract and instant claim 7. The author teaches that nasal mucosal immunization with the NE adjuvant produces Th1 and Th17 immunity; see abstract and instant claim 7. See introduction, p. 2 which teaches that the NE comprises a uniform population of droplets with an average diameter of approximately 350 nm; also see instant claims 8 and 27(a). The author teaches that intranasal administration of the NE have shown to induce robust humoral response with neutralizing antibodies to the protective antigen of anthrax (PA), whole vaccinia virus, whole and split influenza virus, HIV gp120 and HBsAg; see p. 2 of introduction. The author teaches that the mixture of NE with pathogens leads to inactivation of the pathogen due to inherent-surface active nature of the emulsion; see p., 2, introduction and instant claim 2, in part. See p. 2 for “II. Materials and Methods” for describing the ingredients of the NE, or W805EC formulation, as comprising soybean oil, cetyl pyridinium chloride, polysorbate, ethanol and water, and the reconstitution of antigens in PBS; see instant claims 27-31 and in the same amounts recited in the claims. The author teaches the mixing of antigen solutions (comprising PBS) with NE wherein the NE formulation comprises 20 ug of antigen, followed by intranasal immunization of mice on p. 3, under “D. Immunizations”, meeting the limitation that the composition further comprises at least one pharmaceutically acceptable carrier (PBS) of instant claim 10 and intranasal administration of claims 11 and 15, and a method of administration of claim 13. It is noted here that Bielinska teaches that the NE adjuvant may stimulate a Th17 response independent of the source of antigen or the antigen’s molecular properties; see p. 6, para. 1. See p. 2-3 which describes purifying antigens from transfected yeast cells and combining with the NE formulation; see instant claim 16 and 18. See p. 7 for the following recitation: “In summary, our data document that mucosal immunization with NE adjuvant produces innate immune cell activation that helps to direct the induction of Th1 and Th17 cells. This may be important in vaccination for protective cellular immunity against intracellular pathogens, especially on mucosal surfaces.”
Bielinska does not explicitly express administering a composition comprising isolated HSV antigens, including an HSV-1 or HSV-2 surface antigen, including gB and gD (all claims); wherein the HSV antigens are mutants or a fusion (claims 3-6 and 14); wherein the composition further comprises an additional adjuvant (claim 9); wherein the vaccine composition is administered as claimed in claim 12.
Burke describes therapeutic compositions comprising recombinant HSV glycoproteins B and D, including those of HSV types 1 and 2; see abstract, col. 2, lines 43+. Burke describes a composition comprising a mixture of both proteins of type 1 or 2 wherein the proteins may be fused proteins expressing proteins from other pathogens or viruses; see col. 4, lines 20+ and 55+. See claim 1 of this patent which teaches that either a native or a mutant gB and/or gD may be used in the HSV composition. Col. 34, lines 34+ provides a number of different adjuvants which may be used in the composition.
See Baker, para. 18 for describing the nanoemulsion adjuvant W805EC. Para. 299 discloses the following: “In some embodiments, the same route of administration (e.g., mucosal administration) is chosen for both a priming and boosting vaccination. In some embodiments, multiple routes of administration are utilized (e.g., at the same time, or, alternatively, sequentially) in order to stimulate an immune response (e.g., using a composition comprising a nanoemulsion adjuvant and immunogen of the present invention).” See para. 300 for disclosing a mucosal administration of a nanoemulsion adjuvant and an immunogen to a subject in a priming vaccination regimen and a systemic administration of a nanoemulsion adjuvant and an immunogen to a subject in a boosting vaccination regimen; Baker teaches that systemic routes of administration include intramuscular and subcutaneous.
It would have been obvious for one of ordinary skill in the art at the time of the invention to incorporate recombinant HSV antigens, including HSV-1 or HSV-2 gB and gD, in the nanoemulsion taught by Bielinska. One would have been motivated to do so for the advantage of inducing a Th17 response to the antigens in a subject.
It would have been obvious for one of ordinary skill in the art at the time of the invention to further incorporate additional adjuvants in the HSV antigen/NE composition taught by Bielinska and Burke. One would have been motivated to do so for the advantage of further potentiating an immune response in a subject in need thereof, such as, an immunocompromised subject.
It would have been obvious for one of ordinary skill in the art at the time of the invention to further incorporate fusion proteins comprising an HSV antigen fused to another protein of a different virus in the HSV antigen/NE composition taught by Bielinska and Burke. One would have been motivated to do so for the advantage of inducing immunity to more than one antigen in a subject.
It would have been obvious for one of ordinary skill in the art at the time of the invention to use a prime/boost vaccination regimen, wherein the composition is administered via a mucosal route as the prime vaccination regimen, and the composition is administered systemically (e.g. intramuscular administration) as boost vaccination regiment. One would have been motivated to do so for the advantage of stimulating an immune response in a subject.
There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated and commonly used; for example, Bielinska teaches that the NE formulation may be used for different antigens; Burke teaches the use of HSV gB and gD antigens in a therapeutic composition; the use of adjuvants is widely understood and commonly used in the prior art; the preparation of fusion proteins is a technique which widely understood and used; prime/boost is a common vaccination regimen in the art, etc.
The invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the effective time the invention was made.
Applicant argues that no current HSV vaccines, the present claimed invention provides that the antigens are located in the oil core of the nanoemulsion and this protects from degradation and enhances stability and points to Figure 1A-B and Example 3, again mentions no approved vaccines and points to page 2, that the art does not teach this exact combination of vaccine, that Bielinska does not teach mucosal nanoemulsions with at least one HSV antigen, that it is “this exact combination” of antigen and nanoemulsion that produces the unexpected result, that Baker does not cure the deficiencies of Bielinska and Burke and does not teach a successful vaccine.
Applicant’s argument has been fully considered and not found persuasive.
(New claims) As set out in the rejection above, for claim 33 Burke teach combinations of HSV I and II as well as gB and gB and for claim 32 Bielinska teach soybean oil.
Applicant’s argument over no current vaccine is not persuasive because failure of older prior art does not mean all will fail in the future. It seems to be arguing long felt need because of all the failures. To show long felt need applicant must show that their invention solves that problem and that the scope of the claims is commensurate with what provided a solution. Applicant's arguments fail to comply with 37 CFR 1.111(b) because they amount to a general allegation that the claims define a patentable invention without specifically pointing out how the language of the claims patentably distinguishes them from the references.
As far as the location of the antigen and the stability, applicant points to how the nanoemulsion was made. There is no showing of lack of degradation or enhanced stability. Also, the claims do not require an oil core or that the antigen be in it. It seems this would be a property of the nanoemulsion as Example 1 discloses that the antigen is just mixed with the nanoemulsion.
As far as unexpected results, applicant does not point to anything specific in the specification except the prior art summary and that does not show unexpected results of the claimed invention. Also, the arguments of counsel cannot take the place of evidence in the record. In re Schulz, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 43 USPQ2d 1362 (Fed. Cir. 1997) (“An assertion of what seems to follow from common experience is just attorney argument and not the kind of factual evidence that is required to rebut a prima facie case of obviousness.”).
The specific immune response is not persuasive because it is not required of all claims and applicant has not pointed out the specific results that show this compared to the prior art. Bielinska teach that the NE mucosal formulations may be used for different antigens and that induces IL17 response and that is important in protective immune responses in vaccines (intro first paragraph) and has been used for a variety of vaccines that induce a robust immune response including a Th1 and Th17 response (intro para 2).
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Here the “this exact combination” of adjuvant (components and percents) and antigens is not claimed. The claims are drawn to a genus of possible antigens and genus of possible nanoemulsion formulations used and percent compositions of those elements.
The rejection is maintained.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 13-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11, 13, 15 and 16 of U.S. Patent No. 7314624 (cited by the IDS) in further view of Burke (US Patent 5747039-cited by the IDS).
Both sets of claims are directed to a method of administering a composition comprising a nanoemulsion and an antigen, wherein the antigen includes an HSV antigen.
The claims differ in that the nanoemulsion of the ‘624 claims indicate that the nanoemulsion comprises an oil, ethanol, surfactant, quaternary ammonium compound and water. The ‘624 claims are directed to specific oils (claim 6), surfactants (including TWEEN 20 of claim 9) and CPC (claim 13). Claim 16 is directed to HSV-1 or HSV-2 immunogens.
In contrast, the instant claims are not directed to a specific nanoemulsion and instant claim 14 is directed to specific HSV antigens, including gB, gC, gD or gE glycoproteins.
It would have been obvious for one of ordinary skill in the art to incorporate an HSV gB and/or an HSV gD from either HSV-1 or HSV-2 in the composition claimed in the ‘624 patent because Burke describes a therapeutic composition against HSV comprising the HSV gB and gD immunogens.
Applicant argues that the patent does not recite the whole virus, isolated antigen, or the antigen is present in the emulsion and that the application is a species that is not taught.
Applicant’s arguments have been fully considered and not found persuasive.
Here, the patent makes obvious the pending claims because patent claim 16 includes HSV for the virus and claim 15 recites the immunogen is selected from virus or derived from the virus. Additionally, the patent discloses that the immunogens can include proteins and polypeptides (col 11, lines 50-60). Burke teaches therapeutic compositions with gB andgD. One of ordinary skill in the art at the effective time of filing would have been able to choose from art known isolated proteins because claims 15-16 of ‘624 is silent on the specific dervatives to use and had the expectation of success that those isolated proteins have been chosen before. Claim 15 depends on claim 1 and claim 1b of the patent teaches combining nanoemulsion and antigen. Thus, the antigen is within the nanoemulsion. The rejection is maintained.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MYRON G HILL whose telephone number is (571)272-0901. The examiner can normally be reached Mon-Fri.
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MYRON G. HILL
Examiner
Art Unit 1671
/M.G.H/Examiner, Art Unit 1671
/Shanon A. Foley/Primary Examiner, Art Unit 1671
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