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 May 7, 2026 has been entered. Claims 1-4 and 8 have been currently amended. Claims 5-7 have been cancelled. Claims 11-13 were newly added. Claims 1-4, 8 and 11-13 are under consideration in this Office Action.
Withdrawal of Claim Objections
3. The objection of claims 1- 2 is withdrawn in view of applicants amendments.
Withdrawal of Claim Rejections
4. The rejection of claims 1, 3 and 5-8 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph is withdrawn in view of applicants amendments.
5. The rejection of claims 9-10 under 35 U.S.C. 101 is withdrawn in view of applicants amendments.
6. The rejection of Claims 5 and 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over Irvine et al., in view of Tendler et al., is withdrawn in view of applicants amendments.
Claim Rejections
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.
7. Claim 8 and 11-13 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 that infect ruminants, said method comprising administering to an animal a therapeutically effectively amount of the vaccine composition of 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 that infects ruminants, said method comprising administering to a sheep, cattle or goat a therapeutically effective amount of the vaccine composition 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 that infect ruminants, said method comprising administering to an animal a therapeutically effectively amount of the vaccine composition of claim 1. Thus, the claim encompasses treating and preventing all ruminants infection.
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, and/or schistosomiasis. There is no treatment of ascariasis, strongyloidiasis, filariasis, dracunculiasis, trichinosis, cysticercosis, echinococcosis, and/or schistosomiasis after any human or animal was administered the claimed antigens. There are no commercial vaccines for Trichuris trichiura, Ascaris lumbricoides, Strongyloides stercoralis, and Ancylostoma duodenale. 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 ruminant helminthic infection. 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 against ruminants helminth infections, and there is no single vaccine for multiple ruminant 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. There is no universally available commercial vaccine for dracunculiasis in livestock. Biswas et al., (Dracunculiasis (guinea worm disease): eradication without a drug or a vaccine. Philos Trans R Soc Lond B Biol Sci
. 2013 Aug 5;368(1623):20120146. No, there is no vaccine for trichinosis for ruminants such as cattle, sheep, goats. Stachyra et al., (Assessing diagnostic, vaccine and therapeutic potential of selected Trichinella proteins. Food and Waterborne Parasitology. Volume 40, September 2025, e00283). There is no single vaccine or method of preventing all types of ruminants helminth infections. 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. Furthermore, there is no single method of prevention for all helminthic infections for ruminants.
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, 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 ruminant host any each and every different type of ruminant 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 ruminant 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 prevention and treatment method, it would require undue experimentation on the part of the skilled artisan to make and use the claimed 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 Stachyra et al., and Biswas 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 preventative or treating immune response in a ruminant host against ruminant helminth infection commensurate in scope with the claimed invention.
Response to Arguments
8. Applicant's arguments filed May 7, 2026 have been fully considered but they are not persuasive. The rejection of claim 8 and 11-13 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is maintained.
Applicant submits that the "predictability of the art" factor is met because the vaccine formulation is specifically a veterinary vaccine formulation. Contrary to Applicants assertion, Applicants have failed to provide a method of preventing and treating ruminants infections from Trichuris trichiura, Ascaris lumbricoides, Strongyloides stercoralis, and/or Ancylostoma duodenale. Applicants have failed to provide a method of protecting ruminants against Trichuris trichiura, Ascaris lumbricoides, Strongyloides stercoralis, and Ancylostoma duodenale infection. Applicants have failed to provide any scientific evidence that a single composition will treat all ruminant helminth infections.
Applicants urge that the ruminant's immune mechanism remains constant whether challenged by Fasciola, Schistosoma, or Haemonchus, the formulation's efficacy is predictable across helminths that infect these specific hosts. However, the issue is not the ruminants immune mechanism. The issue is that Applicants have failed to describe a single method for the treatment and prevention of infection caused by helminths that infect ruminants, said method comprising administering to an animal a therapeutically effectively amount of the single vaccine composition of claim 1 to treat and prevent all the infections caused by helminths that infect ruminants. Applicants failed to provide a scientific argument or present data that treating all ruminant helminth infections can be prevented the vaccine composition of claim 1.
The specification and incorporated references, such as U.S. Patent No. 5,730,984 (submitted in an Information Disclosure Statement filed herewith), demonstrate that the Sm 14 protein (SEQ ID NO: 1) is a highly conserved fatty acid-binding protein.
Applicants pointed to Fig 6 showing the average ELISA readings of anti-Sm14 IgG antibodies in individual sera from cattle immunized with 80 ug (FIG. 6A) and 160 ug (FIG. 6B) of the rSm14 antigen (dilution 1/800). However, Figure 6 does not show the cattle being infected with a helminth infection. Applicants failed to show whether symptoms were treated or prevented. Applicants failed to show treatment or prevention of the helminth infections within the cattle. At best, Applicants produced an immune response; however eliciting an immune response is not equivalent to a method of treatment or prevention.
Finally, Applicants point to Figure 3 which shows the average ELISA readings of anti-rSm14 IgG antibodies in individual sera from the experiment comparing oil formulations in sheep (dilution 1/2000). Again, Applicants failed to show treatment or prevention of symptoms resulting from a ruminate helminth infections or ruminant helminth infections. Applicants produced an immune response and compared it an oil formulation. Applicants failed to describe a method of treatment or prevention of ruminant helminth infection for ruminants that do not have known vaccines. Furthermore, Applicants have failed to describe a single vaccine composition for prevention and treatment of any type of ruminate helminth infections. Moreover, Applicants failed to describe multiple vaccine compositions for ruminate helminth infections which treat and prevent the infections. Therefore none of Applicants arguments are found persuasive.
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.
9. Claims 1-3, 8 and 11-13 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 a dose, which can be 2 to 4 ml, containing:
from 50 µg to 200 µg of antigen selected from the group consisting of SEQ ID NOs:1-7 0.5 mg to 1 mg of saponin or purified saponin fraction from Quillaja Saponaria;
50 mM of Tris-HCl buffer; and 0.01% of thimerosal, and (b) an oil phase containing:
mineral oil in an amount corresponding to 60% (volume/volume) of the dose; and
10 to 40 mg of a surfactant selected from the group consisting of Cetyl PEG/PPG-10/1 Dimethicone, sorbitan monooleate and polysorbate 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. Thus teaching claim 13. 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; (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 11-12. The vaccine strategy was aimed at the induction of high resistance against Schistosoma infection from S. mansoni. Administration by intradermal/subcutaneous route, high and long-term protection is reached in animals against S. mansoni infection [para 32]. Thus teaching claim 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 intranasal injection and infusion [para 125]. Thus teaching claim 13.
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
Response to Arguments
10. Applicant's arguments filed May 7, 2026 have been fully considered but they are not persuasive. The rejection of claims 1-3, 8 and 11-13 under 35 U.S.C. 103 as being unpatentable over Irvine et al., in view of Tendler et al., is maintained for reasons of record.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, 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.
Applicants argue that Irvine et al., list various formulations without teaching a water in oil emulsion. Contrary to Applicants argument, Irvine et al., clearly teach the adjuvant or adjuvants comprising an immunogenic composition may also include, for example, without limitation, oil emulsions (e.g., Freund's adjuvant); saponin formulations; microbial derivatives; oil emulsions, squalene-water emulsion and/or emulsion of Marcol 52, Span 85 and Tween 85. Therefore, Irvine et al., clearly teach an aqueous phase and an oil phase containing: mineral oil in an amount corresponding to 60% (volume/volume) of the dose; and 10 to 40 mg of a surfactant selected from the group consisting of Cetyl PEG/PPG-10/1 Dimethicone, sorbitan monooleate or and polysorbate 80.
The MPEP section 2123 teaches that patents are relevant as prior art for all they contain, “The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain.” In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989). See also Celeritas Technologies Ltd. v. Rockwell International Corp., 150 F.3d 1354, 1361, 47 USPQ2d 1516, 1522-23 (Fed. Cir.1998) (The court held that the prior art anticipated the claims even though it taught away from the claimed invention. “The fact that a modem with a single carrier data signal is shown to be less than optimal does not vitiate the fact that it is disclosed.”). Therefore applicant’s argument is not persuasive especially when considering 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.
Applicants argue that Tendler does not teach the formulation of SM 14 within the aqueous and oil phase composition. 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). However, the rejection is based upon Irvine et al., in view of Tendler et al. In this case, 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. Into the composition and method as taught by Irvine et al.
Applicants argue that Tendler et al., does not use the water in oil emulsions or the specifically recited reagents. In response to applicant's argument that , the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). In this case, 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 for incorporation into methods of coupling an multi-cellular parasitic pathogen. Therefore, none of Applicants arguments are persuasive because 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.
Applicants point to the superiority of water in oil emulsions with saponin/Quil A. However, superiority is not the issue. In this case, Irvine et al., teach adjuvants comprising an immunogenic composition may also include, for example, without limitation, oil emulsions; saponin formulations; microbial derivatives; oil emulsions, squalene-water emulsion and/or emulsion of Marcol 52®, Span 85 and Tween 85®. Irvine et al., teach the antigen-adjuvant complexes provide an advantage over previous approaches that relied upon non-specific adsorption of antigen to adjuvant. Therefore the prior art teach the advantages associated water in oil emulsions with saponin/Quil A®.
Applicants urge that long term stability and efficacy is not taught or suggested by Irvine or Tendler et al. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies i.e., long term stability and efficacy are not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Thus, the argument is not persuasive.
Applicant points to cross-protection and broad applicability. However, where 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. The evidence relied upon should establish "that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance." Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992) (Mere conclusions in appellants’ brief that the claimed polymer had an unexpectedly increased impact strength "are not entitled to the weight of conclusions accompanying the evidence, either in the specification or in a declaration."); Ex parte C, 27 USPQ2d 1492 (Bd. Pat. App. & Inter. 1992) (Applicant alleged unexpected results with regard to the claimed soybean plant, however there was no basis for judging the practical significance of data with regard to maturity date, flowering date, flower color, or height of the plant.). See also In re Nolan, 553 F.2d 1261, 1267, 193 USPQ 641, 645 (CCPA 1977) and In re Eli Lilly, 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) as discussed in MPEP 716.02(c)."[A]ppellants have the burden of explaining the data in any declaration they proffer as evidence of non-obviousness." Ex parte Ishizaka, 24 USPQ2d 1621, 1624 (Bd. Pat. App. & Inter. 1992). Thus, “[A]ppellants have the burden of explaining the data in a declaration they proffer as evidence of non-obviousness.” Ex parte Ishizaka, 24 USPQ2d 1621, 1624 (Bd. Pat. App. & Inter. 1992). Thus, the argument is not persuasive.
Therefore, the Office has provided 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; and Applicants arguments are not found persuasive.
Claim Rejections - 35 USC § 103
11. Claims 1-4, 8 and 11-13 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 Quillaja saponaria; Tris-HCl buffer; and thimerosal, and an oil phase containing: mineral oil in an amount, a surfactant such as polysorbate 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.
Response to Arguments
12. Applicant's arguments filed May 7, 2026 have been fully considered but they are not persuasive. The rejection of claims 1-3, 8 and 11-13 under 35 U.S.C. 103 as being unpatentable over Irvine et al., in view of CN 101747422 is maintained for reasons of record.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, 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 protein 14 of CN 101747422 in order to provide an effective vaccine for schistosomiasis which would a have huge social and economic benefit as taught by CN101747422.
Applicants urge that Irvine et al., list various formulations without teaching a water in oil emulsion. Contrary to Applicants argument, Irvine et al., clearly teach the adjuvant or adjuvants comprising an immunogenic composition oil emulsions; saponin formulations; microbial derivatives; squalene-water emulsion and/or emulsion of mineral oil. Therefore, Irvine et al., clearly teach an aqueous phase and an oil phase containing: mineral oil in an amount corresponding to 60% (volume/volume) of the dose; and 10 to 40 mg of a surfactant selected from the group consisting of Cetyl PEG/PPG-10/1 Dimethicone, sorbitan monooleate or and polysorbate 80.
Applicants are reminded, The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain. Therefore applicant’s argument is not persuasive especially when considering 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.
Applicants argue that CN 101747422 does not teach the formulation of SM 14 within the aqueous and oil phase composition. 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). However, the rejection is based upon Irvine et al., in view of CN 101747422. In this case, one of ordinary skill in the art would have had a reasonable expectation of success by incorporating the Sm14 protein as taught by CN 101747422, wherein the Sm14 induces high resistance against Schistosoma infection from S. mansoni. Into the composition and method as taught by Irvine et al.
Applicants argue that CN 101747422 does not use the water in oil emulsions or the specifically recited reagents. In response to applicant's argument that the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). In this case, 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 for incorporation into methods of coupling an multi-cellular parasitic pathogen. Thus, Applicants arguments are persuasive because 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 CN 101747422 in order to provide 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.
Applicants argue the superiority of water in oil emulsions with saponin/Quil A. However, superiority is not the issue. In this case, Irvine et al., teach adjuvants comprising an immunogenic composition may also include, for example, without limitation, oil emulsions; saponin formulations; microbial derivatives; oil emulsions, squalene-water emulsion and/or emulsion of Marcol 52®, Span 85 and Tween 85®. Irvine et al., teach the antigen-adjuvant complexes provide an advantage over previous approaches that relied upon non-specific adsorption of antigen to adjuvant. Therefore the prior art teach the advantages associated water in oil emulsions with saponin/Quil A®.
Applicants urge that long term stability and efficacy is not taught or suggested by Irvine or Tendler et al. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies i.e., long term stability and efficacy are not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Thus, the argument is not persuasive.
Applicant points to cross-protection and broad applicability. However, where 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. The evidence relied upon should establish "that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance." Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992) (Mere conclusions in appellants’ brief that the claimed polymer had an unexpectedly increased impact strength "are not entitled to the weight of conclusions accompanying the evidence, either in the specification or in a declaration."); Ex parte C, 27 USPQ2d 1492 (Bd. Pat. App. & Inter. 1992) (Applicant alleged unexpected results with regard to the claimed soybean plant, however there was no basis for judging the practical significance of data with regard to maturity date, flowering date, flower color, or height of the plant.). See also In re Nolan, 553 F.2d 1261, 1267, 193 USPQ 641, 645 (CCPA 1977) and In re Eli Lilly, 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) as discussed in MPEP 716.02(c)."[A]ppellants have the burden of explaining the data in any declaration they proffer as evidence of non-obviousness." Ex parte Ishizaka, 24 USPQ2d 1621, 1624 (Bd. Pat. App. & Inter. 1992). Thus, “[A]ppellants have the burden of explaining the data in a declaration they proffer as evidence of non-obviousness.” Ex parte Ishizaka, 24 USPQ2d 1621, 1624 (Bd. Pat. App. & Inter. 1992). Thus, the argument is not persuasive.
Therefore, the Office has provided 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; and Applicants arguments are not found persuasive.
Pertinent Art
13. 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
14. No claims allowed.
15. THIS ACTION IS MADE FINAL. 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.
16. 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 Peter Paras, can be reached on 571-272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
/JANA A HINES/Primary Examiner, Art Unit 1645
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