DETAILED ACTION
Acknowledgment and entry of the Amendment submitted on 11/10/25 is made.
Claims 17-31, 34, 37 and 38 are currently pending.
Claims 32, 33, 35 and 36 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention.
Claims 17-31, 37 and 38 are currently under examination.
The Declaration under 37 CFR 1.132 by Alejandro Cabezas-Cruz submitted on 11/10/25 has been entered and addressed below.
Claim Rejections - 35 USC § 112-2nd paragraph
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.
Claims 17, 18, 20-23, 25, 26, 28, 29, 30, 31 and 34 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.
Claim 17 is vague and indefinite because the feature "expressing a high level of alpha-Gal" in claim 1 is a relative term which does not allow the skilled reader to discriminate between subject-matter falling inside and outside the scope of the claim. The metes and bounds of this term cannot be understood.
Applicants argue that on page 4 of the Specification, Applicant provided a definite meaning for this term this term, stating: The MFI values were measured according to the said method, as further illustrated in the examples and the obtained results were: E. coli O86:B7 (MFI = 552) - High α-Gal E. coli Nissle EC1917 (MFI = 1092 and 1536 in two experiments) - High α-Gal E. coli O111 (MFI= 1505)- High α-Gal E. coli BL21 (MFI = 346 and 128 in two experiments) - Low a Gal E. coli O128 (MFI = 139) - Low α-Gal E. coli O113 (MFI = 131) - Low α-Gal So an E. coli strain with 'high α-Gal content' or 'expressing high level of α-Gal' according to the present invention is a strain with MFI superior or equal to 500, preferably superior or equal to 530, more preferably superior or equal to 550, in particular according to the protocol as disclosed above. This has been fully and carefully considered but not deemed persuasive. While the specification can be used to provide definitive support, the claims are not read in a vacuum. Rather, the claim must be definite and complete in and of itself. Limitations from the specification will not be read into the claims. The claims as they stand are incomplete and fail to provide adequate structural properties to allow for one to identify what is being claimed.
Claim Rejections - 35 USC § 112-Scope of Enablement
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 17-23, 25, 26, 28-31 and 34 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for:
“A method for preventing and/or reducing the severity of sphaerosporosis in fish comprising orally administering E. coli Nissle 1917 to said fish” (claims 24 and 37)
“A method for preventing and/or reducing aspergillosis in poultry comprising orally administering E. coli O86:B7 or E.coli O111 to said poultry.” (claims 27 and 38)
, does not reasonably provide enablement for:
A method for preventing and/or reducing, in any non-human that does not produce α-Gal, any infectious disease caused by a pathogen expressing α-Gal on its surface, comprising administering to said non-human animal any E. coli strain expressing high level of α-Gal.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
Applicants demonstrated that:
oral administration of E. coli Nissle 1917 in fishes (e.g. common carps), modulates the a-Gal immunity and was able to reduce the severity of sphaerosporosis affecting farmed fish. It decreased the level of α-Gal antibodies in their sera too.
oral administration of Escherichia coli 086:B7 strain, another bacterium expressing high level of a-Gal, protects turkeys against clinical aspergillosis and the formation of lung granulomas by reducing lung anti- α-Gal IgA to residual levels. Whereas these protective effects were not obtained with E. coli BL21, a bacterium expressing residual levels of a-Gal.
Surprisingly, the inventors demonstrated that the protective effect of E. coli O086:B7 was not associated with an increase in circulating anti- α-Gal IgY levels, but with a striking reduction of anti- α-Gal IgA in the lungs of infected turkeys. The same effect was observed with E. coli strain 1917.
The instant claims are broadly drawn to methods for preventing and/or reducing the severity of any infectious disease caused by any pathogen expressing alpha-Gal on its surface by administering any E. coli strain that expresses a ‘high-level’ of α-Gal on its surface. Applicants have effectively taught the strains E. coli Nissle 1917 and E.coli O86:B7 are strains that can treat diseases caused by Sphaerospora monari and Aspergillus, respectively. The application does not provided evidence or working examples of any other strains of E. coli with these properties or experimental results. Further, no other results or treatment of other diseases by pathogens in other non-human animals is provided. The specification does not enable treating the Genus of the myxozoan pathogens, other than S. molnari, recited in claims 22 and 23. Additionally, it would take one of skill in the art undue experimentation to discover and identify other strains of E. coli with the same functional ability and use them in any non-human animal to treat any disease caused by a pathogen expressing α-Gal on it surface. Further, generalization to other E. coli bacterial strains expressing alpha-Gal seems not legitimate in view of the fact that the mechanism of action by which sufficient immunity is generated upon enteral exposition to said bacteria remains not clearly understood. For example, Cruz et al (Expert Review of Vaccines. 15(8): 953-955, August 2, 2016; provided by Applicants) makes clear that not all probiotics expressing alpha-Gal on their surface are able to induce an increase in the levels of anti-alpha-Gal-specific IgG and IgM, and that the proximity of other constituents of bacterial cell wall to the alpha-Gal or the conjugation of alpha-Gal to LPS (or in the case of O86:B7 strain to the O-antigen of LPS, see Soares et al cited above), is likely very relevant in order to obtain an adequate immune response. Evidence has only been shown for the two tested strains.
Genentech Inc. v. Novo Nordisk A/S (CAFC) 42 USPQ2d 1001 clearly states: “Patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable. See Brenner v. Manson, 383 U.S. 519, 536, 148 USPQ 689, 696 (1966) (stating, in context of the utility requirement, that "a patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.") Tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention.”
Response to Applicants’ arguments:
Applicants argue:
The Specification shows that the modulation of anti-α-Gal immunity in very distant species - fish and poultry - can protect these animals from several pathogens producing endogenous α-Gal. The inventors demonstrated that the oral administration of Escherichia coli strains expressing high level of α-Gal, modulate the immunity in non-human animals such as fish and poultry infected by pathogen expressing α-Gal on their cell surface. (Specification at 1.) In particular, they demonstrated that oral administration of bacterium expressing high level of α-Gal in fishes modulated the α-Gal immunity and was able to reduce the severity of disease.
(Id. at 1-2.) The inventors also demonstrated that oral administration of Escherichia coli bacterium expressing high level of α-Gal protects turkeys against clinical aspergillosis and the formation of lung granulomas by reducing lung anti-α-Gal IgA to residual levels. (Id. at 2.) These protective effects were not obtained with Escherichia coli bacterium expressing residual levels of α-Gal. (Id. at 2.) Based on the fact that the mechanism of action is mediated by the modulation of the α-Gal immunity that can occur in all non-human animals lacking endogenous α-Gal (galactose-q-1,3-galactose). i.e., non-human animals that do not naturally produce α- Gal, the skilled artisan would have understood that these results could be extended to all pathogens expressing α-Gal on their cell surface and other non-human hosts that do not naturally produce α-Gal. (Id.) The skilled artisan would expect that E. coli strains with higher α-Gal would perform similarly since the effect was shown to be exhibited at the level of the α-Gal immunity system. Moreover, Applicant submits herewith an additional article by Thorel et al. showing results supporting enablement in penguins. Thorel et al. conducted a trial to test whether oral administration of E. coli Nissle, expressing high a-Gal levels, modulated anti-a-Gal immunity in a colony of Humboldt penguins. They found a strong decrease in anti-a-Gal IgM levels in all animals in the placebo group three months after vaccination protocol, which was not observed in E. coli Nissle-treated penguins. After the vaccination protocol, they found a positive correlation between anti-E. coli IgY and anti-a-Gal IgY in the E. coli Nissle group, suggesting a correlation between the presence of the bacteria and these Abs. Applicant also submits herewith a Declaration regarding the generation of further data supporting enablement. This data demonstrates the protective effect of E. coli Nissle against the pathogens Tetracapsuloides bryosalmonae and Sparicotyle chrysophrii in fish, and demonstrates equally the protective effect of E. coli Nissle against malaria parasites in canaries and red mites in poultry.
These arguments have been fully and carefully considered. However, the specification and Applicants’ arguments are drawn to specific E.coli strains, e.g., E.coli Nissle and Escherichia coli 086:B7. They are also drawn to specific non-human animals, e.g, fish, birds/poultry. They do no include any non-human animal.
Additionally, the arguments do not provide a full citation for “Thorel et al”. It is unclear what publication Applicants are citing. Thorel et al is not provided on any PTO-1449 Information disclosure and no copy is provided.
It would take one of skill in the art undue experimentation to discover and identify other strains of E. coli with the same functional ability and use them in any non-human animal to treat any disease caused by a pathogen expressing α-Gal on it surface. Further, generalization to other E. coli bacterial strains expressing alpha-Gal seems not legitimate in view of the fact that the mechanism of action by which sufficient immunity is generated upon enteral exposition to said bacteria remains not clearly understood. For example, Cruz et al (Expert Review of Vaccines. 15(8): 953-955, August 2, 2016; provided by Applicants) makes clear that not all probiotics expressing alpha-Gal on their surface are able to induce an increase in the levels of anti-alpha-Gal-specific IgG and IgM, and that the proximity of other constituents of bacterial cell wall to the alpha-Gal or the conjugation of alpha-Gal to LPS (or in the case of O86:B7 strain to the O-antigen of LPS, see Soares et al cited above), is likely very relevant in order to obtain an adequate immune response. Evidence has only been shown for the two tested strains. The 1.132 Declaration by Alejandro Cabezas-Cruz provides data that demonstrates the protective effect of E. coli Nissle against the pathogens Tetracapsuloides bryosalmonae and Sparicotyle chrysophrii in fish, and demonstrates equally the protective effect of E. coli Nissle against malaria parasites in canaries and red mites in poultry, e.g., fish and birds/poultry. This data cannot be extrapolated to any E.coli strain expressing “high levels of alpha-Gal” for any infectious disease where the pathogen expresses “high levels of alpha-Gal.” The specification and data does not enable this breadth. It is also unclear when these experiments took place with respect to the priority filing date of June 5, 2020.
Claim Rejections - 35 USC § 112-Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 17-23, 25, 26, 28-31 and 34 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The instant claims are drawn, for example, to:
A method for preventing and/or reducing, in any non-human that does not produce α-Gal, any infectious disease caused by a pathogen expressing α-Gal on its surface, comprising administering to said non-human animal any E. coli strain expressing high level of α-Gal.
The purpose of the "written description" requirement is broader than tomerely explain how to "make and use"; the applicant must convey with reasonableclarity to those skilled in the art that, as of the filing date sought, he or she was inpossession of the invention. The invention is, for purposes of the "writtendescription" inquiry, whatever is now claimed. See Vas-Cath, Inc. v. Mahurkar,935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991).Furthermore, the written description provision of 35 USC § 112 is severable fromits enablement provision; and adequate written description requires more than amere statement that it is part of the invention and reference to a potential methodfor isolating it. The [product] itself is required. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing the invention was 'ready for patenting' such as by disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. Moreover, because the claims encompass a genus of variant species, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was "ready for patenting" by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus'" (Id. at 1106); accordingly, it follows that an adequate written description of a genus cannot be achieved in the absence of a disclosure of at least one species within the genus.
It is noted that MPEP 2111.01 states that "[d]uring examination, the claims must be interpreted as broadly as their terms reasonably allow." In this case, in light of the specification, the examiner has broadly interpreted any non-human animal selected in the group consisting of any non-human animals that do not produce α-Gal, any infectious disease caused by a pathogen expressing α-Gal on its surface, comprising a step of administration in the said non-human animal any E. coli strain expressing high level of a-Gal. The Court of Appeals for the Federal Circuit has recently held that a "written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." University of California v. Eli Lilly and Co., 1997 U.S. App. LEXIS 18221, at *23, quoting Fires v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993). To fully describe a genus of genetic material, which is a chemical compound, applicants must (1) fully describe at least one species of the claimed genus sufficient to represent said genus whereby a skilled artisan, in view of the prior art, could predict the structure of other species encompassed by the claimed genus and (2) identify the common characteristics of the claimed molecules, e.g., structure, physical and/or chemical characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or a combination of these (paraphrased from Enzo Biochemical).University of Rochester v. G.D. Searle & Co. (69 USPQ2d 1886 (2004)) specifically points to the applicability of both Lilly and Enzo Biochemical to methods of using products, wherein said products lack adequate written description. While in University of Rochester v. G.D. Searle & Co. the methods were held to lack written description because not a single example of the product used in the claimed methods was described, the same analysis applies wherein the product, used in the claimed methods, must have adequate written description (see Enzo paraphrased above).
In the instant case, Applicants have not described the genus of claimed strains, infectious pathogens expressing alpha-Gal on their surfaces, such that the specification might reasonably convey to the skilled artisan that Applicants had possession of the broadly claimed invention at the time the application was filed. The Guidelines further state, "[f]or inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus'". The instant specification teaches one strain for poultry and one strain for fishes, and treatment of one specific disease for each. This does not provide adequate written description for the claimed Genus.
The scope of the claim includes numerous structural variants (i.e. different strains, completely different pathogens and animals), and the genus is highly variant because a significant number of structural differences between genus members is permitted. One of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus, and thus, that the applicant was not in possession of the claimed genus. The claimed subject matter is not supported by an adequate written description because a representative number of species has not been described. Based on the lack of knowledge and predictability in the art, those of skill in the art would not conclude that the applicant was in possession of the claimed genus of peptides based on the instant specification.
Applicant is referred to the revised guidelines concerning compliance with the written description requirement of U.S.C. 112, first paragraph, published in the Official Gazette and also available at www.uspto.gov
Response to Applicants’ arguments:
Applicants argue:
Applicant's Specification on page 2: Based on the fact that the mechanism of action is mediated by the modulation of the α-Gal immunity that can occur in all non-human animals lacking endogenous α-Gal (galactose-q-1,3-galactose), i.e. non- human animals that do not naturally produce α-Gal, this invention could be extended to all pathogens expressing α-Gal on their cell surface and other non-human hosts that do not naturally produce α-Gal. In craniates for example, the production of the carbohydrate α-Gal is mediated by the enzyme α-1,3-galactosyltransferase encoded by the gene ggta1 which appeared for the first time in the common ancestor of mammals. Inactivation of the gene ggta1 rendered old world monkeys, apes and humans unable to synthetize α-Gal. Lack of endogenous α- Gal allowed this group of primates to produce high antibody titers against α-Gal, an ability shared by non-mammalian craniates such as fish and birds. Although both the species and the pathogens are very different, they have a common structural feature - the non-human animal does not produce α-Gal, and the pathogen expresses α-Gal on its surface. This allows the claimed invention to use this commonality to effect a modulation of α-Gal immunity. Due to the great differences between these successfully used species and the common mechanism of action, Applicant's specification provides a representative number of species to describe the genus. Accordingly, Applicant submits that the pending claims are fully supported by the specification and respectfully requests withdrawal of the rejection.
These arguments have been fully and carefully considered but are not deemed persuasive. The claims encompass a genus of variant species (any E.coli strain expressing a high level of alpha-Gal to prevent or reduce any infectious disease caused by any pathogen expressing alpha-Gal on its surface), an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus.
In the instant case, Applicants have not described the genus of claimed strains, infectious pathogens expressing alpha-Gal on their surfaces, such that the specification might reasonably convey to the skilled artisan that Applicants had possession of the broadly claimed invention at the time the application was filed. The Guidelines further state, "[f]or inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus'". The instant specification teaches one strain for poultry and one strain for fishes, and treatment of one specific disease for each. This does not provide adequate written description for the claimed Genus.
The scope of the claim includes numerous structural variants (i.e. different strains, completely different pathogens and animals), and the genus is highly variant because a significant number of structural differences between genus members is permitted. One of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus, and thus, that the applicant was not in possession of the claimed genus. The claimed subject matter is not supported by an adequate written description because a representative number of species has not been described. Based on the lack of knowledge and predictability in the art, those of skill in the art would not conclude that the applicant was in possession of the claimed genus of peptides based on the instant specification.
, "Possession may not be shown by merely describing how to obtain possession of members of the claimed ,genus or how to identify their common structural features" (See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895). A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the .gene does (function), rather what it is (structure), see University of California v. Eli Lilly & Co., 43 USPQ2d 1938, thus above claims lack adequate written description.
Applicant is referred to the revised guidelines concerning compliance with the written description requirement of U.S.C. 112, first paragraph, published in the Official Gazette and also available at www.uspto.gov
Claim Rejections - 35 USC § 103
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.
Claim(s) 17-21, 28-31 and 34 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bahtiyar et al (Cell. Elsevier, Amsterdam, NL, 159(6): 1277-1289; Dec. 4, 2014; provided by Applicants) and Soares et al (Trends in Parasitol. 32(2): 120-130, Jan. 13, 2016; provided by Applicants) in view of Barth et al (J. Applied. Microbio. Nov, 1, 2009, 107(5): 1697-1710; provided by Applicants) and Saoud et al, ("EFFICACY OF USING AN ALLOCHTONOUS PROBIOTIC BACTERIUM Escherichia coli Nissle (1917) ON GROWTH AND IMMUNE RESPONSE OF NILE TILAPIA", 22 November 2019 (2019-11-22), XP055748120, Retrieved from the Internet: URL:https://www.was.org/Meeting/ Program/PaperDetail/155848 ; provided by Applicants) and further in view of CRUZ ET AL: "Control of vector-borne infectious diseases by human immunity against [alpha]-Gal", EXPERT REVIEW OF VACCINES, vol. 15, no. 8, August 2, 2016, pages 953-955; provided by Applicants) and CABEZAS-CRUZ ET AL: "Effect of blood type on anti-[alpha]-Gal immunity and the incidence of infectious diseases", EXPERIMENTAL & MOLECULAR MEDICINE, vol. 49, no. 3, March 1, 2017, pages e301.1-e301.7; provided by Applicants).
Bahtivar and Soares disclose administration of microbiota Escherichia coli 086:B7 to mice (non-human) in order to colonize their gut. These mice exhibited resistance to malaria parasites transmitted by mosquitoes. Also disclosed is that the resistance to the pathogen Plasmodium falciparum is mediated by the induction of anti-alpha-gal IgM by E. colli 086:B7. P. falciparum is a pathogen expressing alpha-gal on its surface
However, Bahtivar and Soares do not particularly teach wherein the method involves administering the E. coli strain expressing high levels of α-Gal is to a non-human animal that does not produce α-Gal to prevent or reduce an infectious disease caused by a pathogen that expresses α-Gal on its surface.
Saoud et al teach the administration of probiotic bacterium Escherichia coli Nissle (1917) for improved growth and immune response of Nile Tilapia.
Barth et al discloses the use of E.coli Nissle 1917 for probiotic use in piglets. Pigs do not naturally produce alpha-galactosidase in significant amounts.
Barth and Saoud disclose compositions comprising one of the preferred E. coli strains, E.coli Nissle (1917), which are suitable to be administered to non-human animals. Saoud teaches the administration of E.coli Nissle to fish, e.g., do not express α-Gal.
The cited prior art references already disclose the use of the E. coli strain O86:B7 and/or E.coli Nissle (1917) to treat infection by Plasmodium falciparum. Administration of E.coli Nissle to fish is also taught.
The mechanism by which the instantly claimed method functions was already known or had at least been postulated in the prior art, e.g., Cruz et and Cabezas-Cruz et al. The references teach that the use of probiotic bacteria producing α-Gal as dietary supplements to control vector borne diseases and specifically teach that gut colonization by E.coli O86:B7 induce an increase in the levels of anti-a-Gal-specific IgG and IgM. Accordingly, it would have been prima facie obvious to one of ordinary skill in the art that the administration of E.coli O86:B7 or E. coli Nissle 1917 to fish or other animals in a probiotic would be beneficial and particularly in treating or reducing severity of pathogens, such as Plasmodium falciparum. The effects recited in instant claims 29-31 would be inherent since the method steps are the same. The dosage amounts in claim 34 are typical in the prior art and a result effective variable. It has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value of a result effective variable. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Application of Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980). Since the does often varies according to the animal and situation and different dosages appear to work equally as well, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges in methods disclosed by the prior art by normal optimization procedures known in the probiotic/vaccine art.
Response to Applicants’ arguments:
Applicants argue:
The Examiner concedes that Bahtiyar and Soares do not teach that the method involves administering the E. coli strain expressing high levels of α-Gal is to a non-human animal that does not produce α-Gal to prevent or reduce an infectious disease caused by a pathogen that expresses α-Gal on its surface. Clearly, Bahtiyar and Soares cannot provide any expectation of success. Sauod does not provide this expectation. The Examiner relies on Saoud as teaching, "the administration of probiotic bacterium Escherichia coli Nissle (1917) for improved growth and immune response of Nile Tilapia." However, according to Saoud: "Results showed that EcN doesn't have a significant effect on survival and growth of Nile tilapia Oreochromis niloticus. Hematological parameters suggest an effect on the immune system of the fish offered EcN and but there was no difference in survival between probiotic offered fish and controls with regards to pathogen challenged individuals. It seems the immune response was to the EcN itself." Thus, an effect of E. coli Nissle 1917 for protecting Tilapia (fish) against high levels of α- Gal-positive pathogens is not disclosed. Barth does not provide this expectation. The Examiner relies on Barth as teaching: "Barth et al discloses the use of E. coli Nissle 1917 for probiotic use in piglets. Pigs do not naturally produce alpha-galactosidase in significant amounts." However, Barth only teaches that "EcN colonizes the intestine and persists in conventionally reared piglets for at least 4 weeks upon oral administration." Barth does not teach success with regard the administration of E. coli O86:B7 or E. coli Nissle 1917 to fish or other animals being beneficial in treating or reducing severity of pathogens. Cruz et al (2016) does not provide this expectation. Cruz does not teach success with regard the administration of E. coli O86:B7 or E. coli Nissle 1917 to fish or other animals being beneficial in treating or reducing severity of pathogens. Cruz et al (2016) does not provide this expectation. Cruz does not teach success with regard the administration of E. coli O86:B7 or E. coli Nissle 1917 to fish or other animals being beneficial in treating or reducing severity of pathogens. Cabezas-Cruz et al (2017) does not provide this expectation. Cabezas-Cruz does not teach success with regard the administration of E. coli O86:B7 or E. coli Nissle 1917 to fish or other animals being beneficial in treating or reducing severity of pathogens. Consequently, the Examiner is in error - it would NOT have been "prima facie obvious to one of ordinary skill in the art that the administration of E. coli O86:B7 or E. coli Nissle 1917 to fish or other animals in a probiotic would be beneficial and particularly in treating or reducing severity of pathogens."
Applicants’ arguments have been fully and carefully considered but are not deemed persuasive.
Instant claim 1 recites:
A method for preventing and/or reducing, in any non-human that does not produce α-Gal, any infectious disease caused by a pathogen expressing α-Gal on its surface, comprising administering to said non-human animal any E. coli strain expressing high level of α-Gal.
The claimed method comprises the single active step of administering any E.coli strain expressing high level of alpha-Gal to a non-human animal. Saoud et al teach the administration of probiotic bacterium Escherichia coli Nissle (1917) for improved growth and immune response of Nile Tilapia (fish, non-human do not produce alpha-Gal). Barth et al discloses the use of E.coli Nissle 1917 for probiotic use in piglets. Pigs do not naturally produce alpha-galactosidase in significant amounts (pigs, non-human do not produce alpha-Gal). Accordingly, both Saoud and Barth are actively practicing the claimed method, e.g. administering the identical E.coli strain to a non-human animal. The mechanism by which the instantly claimed method functions was already known or had at least been postulated in the prior art, e.g., Cruz et and Cabezas-Cruz et al. The references teach that the use of probiotic bacteria producing α-Gal as dietary supplements to control vector borne diseases and specifically teach that gut colonization by E.coli O86:B7 induce an increase in the levels of anti-a-Gal-specific IgG and IgM. The secondary references utilize the same active ingredient, E.coli strains, with the identical method step, administering to non-human animals, e.g., fish and poultry.
Instant claims 24, 27, 37 and 38 are not included in this rejection as they do not contain the same breadth of the claims under rejection. See “Status of Claims” below.
Allowable Subject Matter
Claims 24, 27, 37 and 38 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Status of Claims:
No claims are presently allowed.
The prior art does not teach or suggest:
“A method for preventing and/or reducing the severity of sphaerosporosis in fish comprising orally administering E. coli Nissle 1917 to said fish”; and
“A method for preventing and/or reducing aspergillosis in poultry comprising orally administering E. coli O86:B7 to said poultry.”
The beneficial use of these two specific E. coli strains or combinations thereof in poultry or fish that do not produce alpha-Gal to treat or prevent diseases caused by Sphaerospora molnari and Aspergillus pathogens appears to be free of the prior art.
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.
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/JENNIFER E GRASER/Primary Examiner, Art Unit 1645 1/29/26