DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Amendments
2. The amendment filed August 12, 2024 has been entered. Claims 1-10 are under consideration in this Office Action.
Claim Objections
3. Claims 1- 2 are objected to because of the following informalities:
Claim 1 separates the components of the composition using a dash. Where a claim sets forth a plurality of elements or steps, each element or step of the claim should be separated by a line indentation, 37 CFR 1.75(i). There may be plural indentations to further segregate subcombinations or related steps. Therefore, the dashes should be removed and only the period at the completion of the claim should remain. See MPEP 608.01(m).
Claim 2 recites “preferably”. Claim 2 does not recite any other surfactants; therefore it is unclear how the preference is to be used. There are no other surfactant recited, therefore the claim does not need to recite a preference. The Office suggests that the claim specifically recite whether cety1 PEG/PPG-10/1 Dimethicone is required by the claim. 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.
4. Claim 8 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a treatment of Fasciola hepatica, said method comprising administering to a sheep, cattle or goat a therapeutically effective amount of veterinary vaccine composition against helminths comprising: (a) an aqueous phase, corresponding to 40% volume/volume of a dose, at 2 to 4 ml, containing: 50 μg to 200 μg of antigen defined by any of the sequences SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6 or SEQ ID NO: 7; 0.5 mg to 1 mg of saponin based adjuvant; 50 mM of Tris-HCl buffer; and 0.01 % of thimerosal, (b) an oil phase containing: specol oil in an amount corresponding to 60 % (volume/volume) of the dose; 10 to 40 mg of a surfactant selected from Cetyl PEG/PPG-10/1 Dimethicone, sorbitan monooleate and polysorbate 80;
does not reasonably provide enablement for a method for the treatment and prevention of infection caused by helminths, said method employing the vaccine composition as defined in claim 1. 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 or use the invention commensurate in scope with these claims. This is a scope of enablement rejection.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (CAFC 1988),page 1404.
Enablement is considered in view of the Wands factors (MPEP 2164.01 (A)). These include: nature of the invention, breadth of the claims, guidance of the specification, the existence of working examples, state of the art, predictability of the art and the amount of experimentation necessary. In re Fisher, 427 F.2d 833,839, 166 USPQ 18, 24 (CCPA 1970) states, "The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art." "The "amount of guidance or direction" refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictablethe art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling" (MPEP 2164.03). The MPEP further states that physiological activity can be considered inherently unpredictable. Thus, Applicant assumes a certain burden in establishing that inventions involving physiological activity are enabled. All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Nature of the invention: The nature of the invention is a method for the treatment and prevention of infection caused by helminths, said method employing the vaccine composition comprising an antigen defined by any of the sequences SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6 or SEQ ID NO: 7; 0.5 mg to 1 mg of saponin based adjuvant; 50 mM of Tris-HCl buffer; and 0.01 % of thimerosal, an oil phase containing: specol oil in an amount corresponding to 60 % (volume/volume) of the dose; 10 to 40 mg of a surfactant selected from Cetyl PEG/PPG-10/1 Dimethicone, sorbitan monooleate and polysorbate 80, wherein the relative level of skill of those in the art is deemed to be high.
Breadth of the claims: The claims are broadly drawn to a method for the treatment and prevention of infection caused by helminths, said method employing the vaccine composition. Thus, the claim encompasses treating and preventing of any kind of infection caused by helminths wherein the composition is used as a vaccine for inducing a protective immunological response in a subject to all types of helminth infections.
Guidance of the specification/The existence of working examples: The specification teaches a method for treating and preventing helminthic infection. At best, the specification describes a vaccine composition describe Fasciolosis treatment for cattle. There are no protocols provided which demonstrate that the antigen would be effective in protective immunization and prevent helminthiasis, ascariasis, strongyloidiasis, filariasis, dracunculiasis, trichinosis, cysticercosis, echinococcosis, schistosomiasis, and/or enterobiasis. There is no treatment of ascariasis, strongyloidiasis, filariasis, dracunculiasis, trichinosis, cysticercosis, echinococcosis, schistosomiasis, and/or enterobiasis after any human or animal was administered the claimed antigens. There is no teaching as to what the most effective route of administration for the claimed compositions. There is merely a general suggestion of vaccines that do not apply directly to the instant invention. There are no working examples of the claimed antigens prevented any type of helminthic infection in any type of host. Thus, the scope of the scope of the claims is extremely broad compared to the guidance and exemplification provided in the specification. The scope of the claims must bear a reasonable correlation with the scope of enablement. See In re Fisher, 166 USPQ 19 24 (CCPA 1970).
State of the art: The state of the prior art is such that it is well established in the art that there are no vaccines for human use against helminth infections. While vaccines for some helminth infections exist for animals, human vaccines are still in early-stage clinical trials or developmental phases due to the complex life cycles of parasites, immune evasion, and scientific hurdles. Perera et al., (Front Immunol. 2021 Aug 19;12). Helminths are diverse, comprising over 280 species which can infect humans. This number increases dramatically when the one health approach is also considered, including animals. Broadly, these worms are classified into two categories based on morphology: nematodes (roundworms), and platyhelminths (flatworms). The platyhelminths can be further divided into cestodes (tapeworms), and trematodes (flukes). Wong et al., (Acta Trop. 2023 Mar:239:106796) state it has been tested and proven that vaccination is still the best strategy to combat infectious diseases. However, to date, there are still no vaccines against human soil-transmitted helminthic diseases, despite their high prevalence globally, particularly in developing countries and rural areas with tropical climates and poor sanitation. The development of vaccines against helminths is riddled with obstacles. Helminths have a complex life cycle, multiple stages within the same host with stage-specific antigen expression, and the ability to regulate host immune reactions to evade the immune response. These elements contribute to the main challenge of helminthic vaccines: the identification of effective vaccine candidates. Wong et al., findings show that only the hookworm vaccine against N. americanus is even in the clinical trial phase, while the rest is still in exploratory research and pre-clinical development phase.
Therefore, there is no teaching of preventing or even treating every type of helminth infection in any type of subject with a single veterinary vaccine composition. There is no teaching of preventing or treating the onset of symptoms caused by Trichuris trichiura, Ascaris lumbricoides, Strongyloides stercoralis, Necator americanus and Ancylostoma duodenale. There is no teaching of preventing the initial infection. There is no teaching of challenge experiments where any subject was prevented from infection. Thus, the state of the art recognized that it would be highly unpredictable with regard to the method of prevention and treatment by administering a vaccine comprising a single antigen capable of eliciting a protective immune response in any host any each and every different type of helminth infection.
Relative Skill of Those in the Art: One of ordinary skill in the art could not predictably extrapolate the teachings in the specification, limited to method of prevention and/or treatment of all types of helminth infections comprising administering the composition of claim 1, as broadly as claimed. In view of the lack of support in the art and specification for an effective and protective method, it would require undue experimentation on the part of the skilled artisan to make and use the claimed vaccine composition and method of prevention and/or treatment; therefore the full scope of the claims is not enabled.
Thus, the scope of the scope of the claims is extremely broad compared to the guidance and exemplification provided in the specification and the specification fails to teach such. The specification fails to show a single challenge experiment. Therefore the scope of enablement does not embrace a method as instantly claimed. Moreover, there is no teaching as to the general vaccination guidelines or the production of a protective immune response.
The specification does not enable the genus because where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims. In re Soll, 97 F.2d 623, 624, 38 USPQ 189, 191 (CCPA 1938). In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) (contrasting mechanical and electrical elements with chemical reactions and physiological activity). See also In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); In re Vaeck, 947 F.2d 488, 496, 20 USPQ2d 1438, 1445 (Fed. Cir. 1991). This is because it is not obvious from the disclosure of one particular species, what other species will work. See MPEP 2164.03. One of skill in the art would neither expect nor predict the appropriate functioning of the method as broadly as is claimed. Without such guidance, the method is unpredictable and the experimentation left to those skilled in the art is unnecessarily and improperly extensive and undue. See Amgen, Inc. v. Chugai Pharmaceutical Co. Ltd., 927 F, 2d 1200, 18 USPQ 1016 (Fed. Cir. 1991) at 18 USPQ 1026 1027 and Ex parte Forman, 230 USPQ 546 (BPAI 1986).
In view of the lack of the predictability of the art to which the invention pertains as evidenced by Perera et al., and Wong et al., the lack of guidance and direction provided by applicant, and the absence of working examples, undue experimentation would be required to practice the claimed method with a reasonable expectation of success, absent a specific and detailed description in applicant’s specification of how to effectively inducing a protective immune response in a specific host against , commensurate in scope with the claimed invention.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
5. Claims 1, 3 and 5-8 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1 and 3 contains the trademark/trade name QuilA®, Tween® 80, Marcol™ 52, Span®80. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe Saponin based adjuvant, Polysorbate 80, Specol and sorbitan monooleate, accordingly, the identification/description is indefinite.
Claims 1, 4 and 6 recites alternative limitations which are improperly expressed. Alternative expressions are permitted if they present no uncertainty or ambiguity with respect to the question of scope or clarity of the claims. One acceptable form of alternative expression, which is commonly referred to as a Markush group recites members as being “selected from the group consisting of A, B and C”. Another acceptable form recites “selected from 1, 2, 3, or 4.” Applicant may correct this by amending the claim to recite the appropriate language.
Claim 1 recites the limitation "the dose" in the claim. There is insufficient antecedent basis for this limitation in the claim.
Claims 5-7 are not further limiting. None of claims 5-7 incorporate any additional ingredients to further limit the components of the veterinary composition. Clarification is required to overcome the rejection.
Claim 8 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted steps are:
Claim 8 does not recite administering the composition of claim 1 to any kind of subject, or animal. Claim 8 does not recite an amount of composition needed to treat or prevent an infection caused by helminths. It is suggested the administered about be recited as an effective amount or therapeutic amount depending upon the recitation within the instant specification. Clarification is required to overcome the rejection.
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.
6. Claims 9-10 are rejected under 35 U.S.C. 101 because the claimed invention is not supported by either a asserted utility or a well-established utility.
Claims 9-10 are also rejected under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph. Specifically, because the claimed invention is not supported by either a asserted utility or a well-established utility for the reasons set forth above, one skilled in the art clearly would not know how to use the claimed invention.
Claim Rejections - 35 USC § 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.
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.
7. Claims 1-3 and 5-10 are rejected under 35 U.S.C. 103 as being unpatentable over Irvine et al., (US 20190358312 published 2019-11-28; priority to Dec. 19, 2017) in view of Tendler et al., (US Pub 20070021332 published 2007-02-25; priority to 20004-01-30).
The claims are drawn to a veterinary vaccine composition against helminths characterized by comprising: (a) an aqueous phase, corresponding to 40% (volume/volume) of the dose, which can be 2 to 4 ml, containing:
from 50 µg to 200 µg of antigen; 0,5 mg to 1 mg of saponin or Quil-A®;
50 mM of Tris-HCl buffer; and 0.01% of thimerosal, (b) an oil phase containing:
Marcol 52™ oil in an amount corresponding to 60% (volume/volume) of the dose;
10 to 40 mg of a surfactant selected from Cetyl PEG/PPG-10/1 Dimethicone, Span® 80 or Tween® 80.
Irvine et al., describe compositions and methods for coupling an antigen to an adjuvant, immunogenic compositions and vaccines [abstract]. Antigens suitable for inclusion in the immunogenic compositions described herein may be derived from any pathogen such as a multi-cellular parasitic pathogen [para 189]. Exemplary multicellular parasitic pathogens include, e.g., trematodes (flukes) [para 194]. The antigen-adjuvant coupling reagents, antigens, optionally linkers, and adjuvants, described herein, are suitable for use in the antigen-adjuvant complexes and in immunogenic compositions or as components in vaccines. The immunogenic compositions disclosed herein may include an antigen-adjuvant complex, optionally a linker, a second adjuvant, or a combination thereof [para 200]. In some embodiments, kits are provided for producing a single-dose administration unit [para 238]. Irvine et al., describe saponin adjuvants. An ISCOM-like nanoparticle comprised of self-assembled cholesterol, phospholipid, and Quillaja (Quil-A) saponin was prepared for some immunizations [para 290]. Irvine et al., teach 5 μg saponin adjuvant, 5 μg antigen mixed with 50 μg alum in 100 μL PBS [para 287]. In some embodiments, acceptable formulation materials preferably are nontoxic to recipients at the dosages and concentrations employed. In certain embodiments, the formulation material(s) are for s.c. and/or I.V. administration. In some embodiments, the pharmaceutical composition can contain formulation materials for modifying, maintaining or preserving, for example, the pH, osmolality, viscosity, clarity, color, isotonicity, odor, sterility, stability, rate of dissolution or release, adsorption or penetration of the composition. In some embodiments, suitable formulation materials include, buffers such as Tris-HCl preservatives such as thimerosal; suspending agents; surfactants or wetting agents such as polysorbate 80 [para 227]. Aluminum salts and “Adjuvant System 04” (AS04) are two adjuvants used in commercially available vaccines in the United States. Tween 80 (0.2%); polysorbate 80 (Tween 80); Quil-A (Quil-A saponin); Specol (emulsion of Marcol 52™, Span 85 and Tween 85) [para 198]. The adjuvant or adjuvants comprising an immunogenic composition may also include, without limitation, oil emulsions [para 204]. Therefore, Irvine et al., teach a veterinary vaccine composition against helminths characterized by comprising: (a) an aqueous phase, containing: parasitic fluke antigen; saponin or Quil-A®; Tris-HCl buffer; and thimerosal, and an oil phase containing: Marcol 52™ oil in an amount, a surfactant such as Span 80 or Tween® 80; however Irvine et al., does not teach the specific fluke antigen as Sm14.
Tendler et al., teach an effective vaccine will be the most powerful method, with a better cost/benefit relation, stopping the disease transmission and eradicating it from the human context regarding schistosomiasis; and from the veterinary context regarding fascioliasis [para 19]. This a vaccine against Fasciola hepatica infections in bovine, caprine, and ovine cattle [para 45]. Thus teaching claims 5-6 and 10. The vaccine strategy was aimed at the induction of high resistance against Schistosoma infection from S. mansoni . Administration by intradermal/subcutanecus route, high and long-term protection is reached in animals against S. mansoni infection [para 32]. Thus teaching claims 7-8. It will be demonstrated here, the capacity of the Sm14 protein's recombinant mutant forms provide high protection against infections by Fasciola hepatica and Schistosoma mansoni, as well as all the remaining species of Schistosoma and Echinococcus and potentially other helminths supposedly pathogenic in relation to humans and animals [para 74]. A vaccinal antigen should be a homogeneous parasite-preserved component presenting no great differences in its structure and primary amino acids sequence, so that the immune response against this antigen (and the organism presenting it) be also the most homogeneous and effective in the vaccinated mammal [para 75]. Administration other than enteral and topical administration, usually by injection, and include, without limitation, intravenous, intranasal, intraocular, intramuscular, intraarterial, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, intracarotid and intrasternal injection and infusion [para 125].
The adjuvants used accordingly to present invention may be selected among Quil®A; however, any other similar adjuvants may be employed in the formulation [para 118]. The Comparative Table shows that mutant proteins planned (Sm14-M20S62 and Sm14-M20V62) present protection levels comparable with the Sm14-M20 original protein (Sm14-M20C62). The advantage of mutants, in their use as a base of a helminth vaccine, does not lay in providing higher protection levels but in maintaining the structural integrity of the vaccine's active ingredient (Sm14) and for more time [para 119]. Tendler et al., teach 100% sequence identity for claims 1 and 9.
Therefore, it would have been prima facie obvious at the time of applicants invention to modify the fluke vaccine of Irvine et al., to incorporate to the Schistosoma mansoni protein 14 of Tendler et al., in order to provide an effective vaccine with a better cost/benefit relation, stopping the disease transmission and eradicating it from human and schistosomiasis; and from the veterinary context regarding fascioliasis as taught by Tendler et al. One of ordinary skill in the art would have had a reasonable expectation of success by incorporating the Sm14 protein as taught by Tendler et al., wherein the Sm14 induces high resistance against Schistosoma infection from S. mansoni. Additionally, one of ordinary skill in the art would have a reasonable expectation of success by incorporating the Sm14 proteins which provide high protection against infections by Fasciola hepatica, Schistosoma mansoni, Schistosoma and Echinococcus and potentially other helminths supposedly pathogenic in relation to humans and animals.
It is noted, that while the references recite the combination of adjuvants, preservatives, buffers, and the like at specific amounts; neither specifically recite the recited quantities. Regarding the specific amounts recited in the instant claims, MPEP 2144.05 states, "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997)."
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses combining prior art elements according to known methods to yield predictable results, thus the combination is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "The combination of familiar element according to known ingredients is likely to be obvious when it does no more than yield predictable results". It is well known to take a vaccine comprising well known buffers, adjuvants and preservatives, where there is no change in the respective function of the components; thus the combination would have yielded a reasonable expectation or success along with predictable results to one of ordinary skill in the art at the time of the invention. Therefore, it would have been obvious to a person of ordinary skill in the art to combine prior art elements according to known ingredients that is ready for improvement to yield predictable results. The claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
ALGINMENT OF INSTANT SEQ ID NO:1
ADR50948
ID ADR50948 standard; protein; 133 AA.
AC ADR50948;
XX
DT 15-OCT-2009 (revised)
DT 15-JUN-2007 (revised)
DT 04-NOV-2004 (first entry)
XX
DE Schistosoma mansoni 14.8 kD Sm14 protein.
KW schistosomicide; antihelmintic; vaccine; Sm14 recombinant protein;
KW protecting antigen; helminth infection; human; animal;
KW Fasciola infection; schistosomiasis; fascioliasis; BOND_PC;
KW fatty acid binding protein; fatty acid-binding protein Sm14; GO5488;
KW GO6810; GO8289.
XX
OS Schistosoma mansoni.
XX
CC PN WO2004067698-A2.
CC PD 12-AUG-2004.
CC PF 30-JAN-2004; 2004WO-BR000005.
PR 31-JAN-2003; 2003BR-00003266.
CC PA (FIOC-) FIOCRUZ FUNDACAO CRUZ OSWALDO.
CC PI Tendler M, Katz N, Simpson AJ, Raw I, Ho PL, Ramos CRR;
XX
DR WPI; 2004-594192/57.
DR PC:NCBI; gi256088632.
DR PC:SWISSPROT; P29498.
DR PC:BIND; 302630, 302629.
XX
CC PT Novel Schistosoma mansoni recombinant protein of specific molecular
CC PT weight, useful as protecting antigen against Schistosoma and Fasciola
CC PT infection affecting humans and animals.
XX
CC PS Disclosure; SEQ ID NO 1; 66pp; English.
CC The invention relates to a Schistosoma mansoni 14.8 kD (Sm14) recombinant
CC protein (I) comprising any one of 4 fully defined sequences of 133 amino
CC acids as given in the specification, where (I) used as a protecting
CC antigen against the helminth infection that affects humans and animals.
CC (I) is useful as a protecting antigen against helminth infection that
CC affects humans and animals. Compositions (II) containing (I) are useful
CC for inducing protection against helminth, e.g., Schistosoma infection,
CC preferably Schistosoma mansoni infection, or Fasciola infection,
CC preferably Fasciola hepatica infection, which involves administering one
CC or more doses of (II) to the mammal. (II) is useful for preventing from
CC Schistosoma infection, preferably Schistosoma mansoni infection or
CC Fasciola infection, preferably Fasciola hepatica infection, which
CC involves administering one or more doses of (II) to a mammal. (I) is
CC useful as a vaccine for schistosomiasis and fascioliasis. This sequence
CC corresponds to a Sm14 protein from Schistosoma mansoni and used in the
CC invention.
CC
CC Revised record issued on 15-OCT-2009 : Enhanced with precomputed
CC information from BOND.
XX
SQ Sequence 133 AA;
ALIGNMENT:
Query Match 100.0%; Score 681; Length 133;
Best Local Similarity 100.0%; Matches 133; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MSSFLGKWKLSESHNFDAVMSKLGVSWATRQIGNTVTPTVTFTMDGDKMTMLTESTFKNL 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MSSFLGKWKLSESHNFDAVMSKLGVSWATRQIGNTVTPTVTFTMDGDKMTMLTESTFKNL 60
Qy 61 SCTFKFGEEFDEKTSDGRNVKSVVEKNSESKLTQTQVDPKNTTVIVREVDGDTMKTTVTV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SCTFKFGEEFDEKTSDGRNVKSVVEKNSESKLTQTQVDPKNTTVIVREVDGDTMKTTVTV 120
Qy 121 GDVTAIRNYKRLS 133
|||||||||||||
Db 121 GDVTAIRNYKRLS 133
ALGINMENT OF INSTANT SEQ ID NO:2
ID ADR50952 standard; protein; 133 AA.
AC ADR50952;
XX
DT 15-JUN-2007 (revised)
DT 04-NOV-2004 (first entry)
XX
DE Schistosoma mansoni 14.8 kD Sm14 protein recombinant #4.
KW schistosomicide; antihelmintic; vaccine; Sm14 recombinant protein;
KW protecting antigen; helminth infection; human; animal;
KW Fasciola infection; schistosomiasis; fascioliasis; BOND_PC;
KW Sm14 fatty acid-binding protein isoform T20;
KW Sm14 fatty acid-binding protein isoform T20 [Schistosoma mansoni];
KW GO5488; GO6810; GO8289.
OS Schistosoma mansoni.
OS Synthetic.
XX
CC PN WO2004067698-A2.
CC PD 12-AUG-2004.
CC PF 30-JAN-2004; 2004WO-BR000005.
PR 31-JAN-2003; 2003BR-00003266.
XX
CC PA (FIOC-) FIOCRUZ FUNDACAO CRUZ OSWALDO.
CC PI Tendler M, Katz N, Simpson AJ, Raw I, Ho PL, Ramos CRR;
XX
DR WPI; 2004-594192/57.
DR PC:NCBI; gi20270934.
DR PC:SWISSPROT; P29498.
XX
CC PT Novel Schistosoma mansoni recombinant protein of specific molecular
CC PT weight, useful as protecting antigen against Schistosoma and Fasciola
CC PT infection affecting humans and animals.
CC PS Claim 1; SEQ ID NO 5; 66pp; English.
XX
CC The invention relates to a Schistosoma mansoni 14.8 kD (Sm14) recombinant
CC protein (I) comprising any one of 4 fully defined sequences of 133 amino
CC acids as given in the specification, where (I) used as a protecting
CC antigen against the helminth infection that affects humans and animals.
CC (I) is useful as a protecting antigen against helminth infection that
CC affects humans and animals. Compositions (II) containing (I) are useful
CC for inducing protection against helminth, e.g., Schistosoma infection,
CC preferably Schistosoma mansoni infection, or Fasciola infection,
CC preferably Fasciola hepatica infection, which involves administering one
CC or more doses of (II) to the mammal. (II) is useful for preventing from
CC Schistosoma infection, preferably Schistosoma mansoni infection or
CC Fasciola infection, preferably Fasciola hepatica infection, which
CC involves administering one or more doses of (II) to a mammal. (I) is
CC useful as a vaccine for schistosomiasis and fascioliasis. This sequence
CC corresponds to a recombinant Sm14 protein from Schistosoma mansoni and
CC used in the invention.
CC
CC Revised record issued on 15-JUN-2007 : Enhanced with precomputed
CC information from BOND.
XX
SQ Sequence 133 AA;
ALGINMENT OF INSTANT SEQ ID NO: 3
ID ADR50951 standard; protein; 133 AA.
AC ADR50951;
CC PN WO2004067698-A2.
SQ Sequence 133 AA;
Query Match 100.0%; Score 680; Length 133;
Best Local Similarity 100.0%;
Matches 133; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MSSFLGKWKLSESHNFDAVASKLGVSWATRQIGNTVTPTVTFTMDGDKMTMLTESTFKNL 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MSSFLGKWKLSESHNFDAVASKLGVSWATRQIGNTVTPTVTFTMDGDKMTMLTESTFKNL 60
Qy 61 SCTFKFGEEFDEKTSDGRNVKSVVEKNSESKLTQTQVDPKNTTVIVREVDGDTMKTTVTV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SCTFKFGEEFDEKTSDGRNVKSVVEKNSESKLTQTQVDPKNTTVIVREVDGDTMKTTVTV 120
Qy 121 GDVTAIRNYKRLS 133
|||||||||||||
Db 121 GDVTAIRNYKRLS 133
Claim Rejections - 35 USC § 103
8. Claims 1-10 are rejected under 35 U.S.C. 103 as being unpatentable over Irvine et al., (US 20190358312 published 2019-11-28; priority to Dec. 19, 2017) in view of CN 101747422 (published 2010-06-23; priority to 2008-12-11).
Irvine et al., has been discussed above as teaching a veterinary vaccine composition against helminths characterized by comprising: (a) an aqueous phase, containing: parasitic antigen; saponin or Quil-A®; Tris-HCl buffer; and thimerosal, and an oil phase containing: Marcol 52™ oil in an amount, a surfactant such as Span 80 or Tween® 80; however Irvine et al., does not teach the specific antigen.
CN 101747422 teach Schistosoma japonicum fatty acid binding protein of the present invention can be applied to the preparation of schistosomiasis vaccines [abstract]. The purposes of Japanese schistosome fatty acid-binding protein, can be applicable to prepare blood fluke vaccine as immunogen [Summary of Invention]. CN 101747422 teach the antigen with Tris-HCl and other buffers [Embodiment]. CN 101747422 teach Schistosoma sequences SEQ ID NO:1 with 99.0%, SEQ ID NO:2 with 98.1%, SEQ ID NO:3 with 98.2%, SEQ ID NO:4 with 98.2% and SEQ ID NO: 5 with 98.2% sequence identity.
ALGINMENT OF INSTANT SEQ ID NO:6
D AYF73626 standard; protein; 132 AA.
AC AYF73626;
XX
DT 30-SEP-2010 (first entry)
XX
DE Fasciola hepatica fatty acid binding protein type 3.
XX
KW FABP3; Fatty acid binding protein type 3; antibody production;
KW diagnostic test; drug screening; gene therapy; vaccine, antiparasitic;
KW BOND_PC; fatty acid binding protein; GO5488; GO6810; GO8289.
XX
OS Fasciola hepatica.
XX
CC PN CN101747422-A.
XX
CC PD 23-JUN-2010.
XX
CC PF 11-DEC-2008; 2008CN-10044088.
XX
PR 11-DEC-2008; 2008CN-10044088.
XX
CC PA (SHAN-) SHANGHAI HUMAN GENE TEAM RES CENT.
XX
CC PI Feng Z, Cn, Han Z, Cn, Hu W, Cn, Liu F, Cn;
XX
DR WPI; 2010-J67778/51.
DR SWISSPROT; Q9U1G6.
DR PC:NCBI; gi47116941.
DR PC:SWISSPROT; Q9U1G6.
XX
CC PT New fatty acid binding protein of Schistosoma japonicum, useful for
CC PT preparing schistosoma vaccine and anti-schistosoma antibody, for
CC PT selecting a medicament, and in serodiagnosis and gene therapy.
XX
CC PS Disclosure; Fig 2; 12pp; Chinese.
XX
CC The present invention relates to a novel Schistosoma japonicum fatty acid
CC binding protein. The present invention also provides a gene encoding the
CC Schistosoma japonicum fatty acid binding protein. The Schistosoma
CC japonicum fatty acid binding protein is useful: for preparing Schistosoma
CC vaccine and anti-Schistosoma antibody; and for selecting a medicament. It
CC is also used in serodiagnosis and gene therapy. The present sequence is a
CC Fasciola hepatica cytoplasmic fatty acid binding protein type 3 which is
CC used in the invention.
CC
CC Revised record issued on 25-SEP-2010 : Enhanced with prec
CC
CC
CC Revised record issued on 25-SEP-2010 : computed information from BOND.
XX
SQ Sequence 132 AA;
Query Match 100.0%; Score 665; Length 132; Best Local Similarity 100.0%;
Matches 132; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MANFVGSWKLEQSENMDAVLQKLGINVIKRKLITSSKPEITFTLEGNKMTMKTVSALKTT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MANFVGSWKLEQSENMDAVLQKLGINVIKRKLITSSKPEITFTLEGNKMTMKTVSALKTT 60
Qy 61 VISFTFGEEFKEETADGRTVMTTFTKDSDSKISQVQKCPENTTHVVREVTGGKMIATVTV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 VISFTFGEEFKEETADGRTVMTTFTKDSDSKISQVQKCPENTTHVVREVTGGKMIATVTV 120
Qy 121 GDVKAVNNYHKV 132
||||||||||||
Db 121 GDVKAVNNYHKV 132
Therefore, it would have been prima facie obvious at the time of applicants invention to modify the fluke vaccine of Irvine et al., to incorporate to the Schistosoma fluke of CN101747422 in order to provide an effective vaccine for schistosomiasis which would a have huge social and economic benefit as taught by CN101747422. One of ordinary skill in the art would have had a reasonable expectation of success by incorporating the Schistosoma protein as taught by CN101747422 wherein the antigen can disturb bilharzial immune evasion mechanism enhancing host's immunity to kill function because suppress these albumen. Additionally, one of ordinary skill in the art would have a reasonable expectation of success by incorporating the protein which provide a blood fluke vaccine as immunogen.
It is noted, that while the references recite the combination of adjuvants, preservatives, buffers, and the like at specific amounts; neither specifically recite the recited quantities. Regarding the specific amounts recited in the instant claims, MPEP 2144.05 states, "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997)."
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses combining prior art elements according to known methods to yield predictable results, thus the combination is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "The combination of familiar element according to known ingredients is likely to be obvious when it does no more than yield predictable results". It is well known to take a vaccine comprising well known buffers, adjuvants and preservatives, where there is no change in the respective function of the components; thus the combination would have yielded a reasonable expectation or success along with predictable results to one of ordinary skill in the art at the time of the invention. Therefore, it would have been obvious to a person of ordinary skill in the art to combine prior art elements according to known ingredients that is ready for improvement to yield predictable results. The claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Pertinent Art
9. The prior art made of record and not relied upon is considered pertinent to applicant’s disclosure.
Mendes et al., (Mem. Inst. Oswaldo Cruz 105 (5) • Aug 2010). Mendes et al., teach the evaluation of local immune response to Fasicola hepatica experimental infection in the liver and hepatic lymph nodes of goats immunized with Sm14 vaccine antigens. The goats were immunized with Quillaia A (Quil A)] and group 3 (immunized with rSm14 in Quil A and infected), each containing seven animals. Immunization with rSm14 in Quil A adjuvant induced a reduction in gross hepatic lesions and reduced hepatic and HLN infiltration of CD2+, CD4+, CD8+ and γ´+ T lymphocytes as well as IL-4+ and IFN-γ+ cells. This is the first report of caprine immunization against F. hepatica using a complete rSm14 molecule derived from S. mansoni. Immunization reduced hepatic damage and local inflammatory infiltration into the liver and HLN.
Tendler et al., (US 5730984 published 1998-03-24) teach an immunogenic composition able to confer at least partial protection against infection with pathogenic helminths, comprising an effective amount of an isolated SM-14 protein and a pharmaceutically acceptable carrier, wherein the SM-14 protein is a 14 KD fatty acid binding protein of Schistosoma mansoni.
Stephenson et al., Schistosome vaccine adjuvants in preclinical and clinical research vaccines (Basel) 2014. Vol. 2, no. 3, pages 654-85.
WO 1993023542 Graham et al., teach sequences encoding helminth aminopeptidase enzymes, and antigenic fragments and functionally-equivalent variants thereof, their use in the preparation of vaccines for use against helminth parasites.
US 20100281552 Encell et al., teach 100% sequence identity to SEQ ID NO: 2, SEQ ID NO:3, and SEQ ID NO:5.
WO2005023979 Verjovski et al., teach 100% sequence identity to SEQ ID NO: 1.
DE44192642 Tendler et al., teach 100% sequence identity to SEQ ID NO: 1.
WO2004067698 Tendler et al., teach 100% sequence identity to SEQ ID NO: 3.
WO 2018132882 Tendler et al., teach 100% sequence identity to SEQ ID NO: 5.
WO 2012034197 Ramos et al., teach 100% sequence identity to SEQ ID NO: 5.
CN101747422 Feng et al., teach 100% sequence identity to SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:6.
Conclusion
10. No claims allowed.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JA-NA A HINES whose telephone number is (571)272-0859. The examiner can normally be reached Monday thru Thursday.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor Dan Kolker, can be reached on 571-272-3181. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JANA A HINES/Primary Examiner, Art Unit 1645