DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application claims benefit of priority to Provisional Application 62/213,564 filed 09/02/2025 and is also a 371 of PCT/US2016/049439 filed 08/30/2016. This application is also a Continuation of Applications 15/755,711 filed 02/27/2018 and 17/172,923 filed 02/10/2021.
Drawings
The Drawings filed 02/28/2024 are accepted by the Examiner.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-13 and 18, in the reply filed on 05/07/2026 is acknowledged. Regarding the election of species, Applicant elected Bifidobacterium bifidum as the particular glycoside hydrolase, Lactobacillus as the particular direct fed microbial, a subtilisin-type serine protease as the particular protease, a granular form as the specific form of the elected glycoside hydrolase and an animal feed as the particular form of the mixture of components. All elections of species were made without traverse.
Amendments and Claim Status
In the reply filed 05/07/2026, Applicant canceled claims 14-17 and 19-26 and amended claim 1.
Claims 1-13 and 18 are currently pending and under examination.
Specification Objections
The title is objected to because the title contains a misspelling. The title recites “Glycoside hydolases” but should recite “glycoside hydrolases.” Appropriate correction is required.
Claim Objections
Claims 1-13 and 18 are objected to because of the following informalities: Claim 1-13 and 18 lack punctuation separating the preamble of the claim from the body of the claim. For example, claim 2 should recite “the method of claim 1, wherein the glycoside hydrolase is an alpha-L-fucosidase.” Appropriate correction is required.
Claim 2 is objected to because of the following informalities: Claim 2 recites “an alpha-L-fucososidase” in lines 1-2 of the claim. ‘Fucososidase’ is misspelled. Appropriate correction is required.
Claim 4 is objected to because of the following informalities: Claim 4 is missing a space after the recitation of ‘(a)’ in the phrase “… capable of (a)converting …” in line 3 of the claim and is missing the word ‘a’ after ‘to’ in the phrase “converting a blood group B antigen to blood group H antigen.” Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 4, 8 and 10-12 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 4 recites the limitation “wherein the alpha-L-fucosidase is capable of removing a terminal alpha-1,2-linked fucose group from a glycan-containing structure either alone or in combination with an enzyme capable of (a)converting a blood group A antigen to a blood group H antigen or (b) converting a blood group B antigen to blood group H antigen” in lines 1-4 of the claim. This limitation is unclear. It appears the first two lines are attempting to limit the alpha-L-fucosidase to being able to remove a terminal alpha-1,2-linked fucose group from a glycan-containing structure. However, it is unclear what the second two lines are trying to limit. It is unclear if a second enzyme that can convert blood groups is being given in combination with the alpha-L-fucosidase or if the alpha-L-fucosidase provides this function with the addition of an additional enzyme or something else. Thus, claim 4 is generally unclear.
Claim 8 recites the limitation "wherein the alpha-L-fucosidase is encapsulated" in lines 1-2. Claim 1, the claim from which claim 8 depends, does not recite an alpha-L-fucosidase, just glycoside hydrolase. Thus, there is insufficient antecedent basis for this limitation in the claim.
Claim 10 recites the limitation "the alpha-L-fucosidase and/or the direct fed microbial and/or the protease" in lines 1-2. Claim 1, the claim from which claim 10 depends, does not recite an alpha-L-fucosidase, a direct fed microbial or a protease. Thus, there is insufficient antecedent basis for this limitation in the claim.
Claim 11 recites the limitation "the protease" in line 2. Claim 6, the claim from which claim 11 depends, does not recite a protease. Thus, there is insufficient antecedent basis for this limitation in the claim.
Claim 12 recites the limitation "the alpha-L-fucosidase" in line 1. Claim 1, the claim from which claim 12 depends, does not recite an alpha-L-fucosidase. Thus, there is insufficient antecedent basis for this limitation in the claim.
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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-4, 8, 10 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Klock (WO 1994025061 A1, 11/10/1994) in view of Katayama et al. (Journal of Bacteriology, 08/2004).
Regarding claims 1-4, Klock discloses methods and compositions for the treatment and/or prevention of a variety of diseases (See entire document, Abstract). The methods involve the administration of an effective amount of a therapeutic catalyst wherein the therapeutic catalyst is an enzyme (Abstract). The therapeutic catalyst catalyzes a reaction that results in the structural alteration of at least one member of a receptor binding pair of molecules whereby the interaction between the receptor and the binding pair is disrupted (Abstract). Many infectious diseases involve the interaction of receptors present on a microorganism with carbohydrates or glycoconjugates present on cells in a host (Page 9, Lines 20-25). Interference with the interaction of receptor binding pair members, where one of the binding pair members is present on an infectious organism, can be achieved by utilizing a therapeutic catalyst to catalyze a chemical reaction that modifies a binding pair member so as to interfere with the interaction between binding pair members (Page 9, Lines 28 – Page 10, Lines 1-2). Klock further discloses a therapeutic catalyst is a carbohydrate modifying enzyme wherein the therapeutic catalyst catalyzes a reaction in which a carbohydrate is structurally modified (Page 6, Line 34 – Page 7, Lines 1-10). Carbohydrate modifying enzymes are enzymes that catalyze a reaction that may alter the structure of a carbohydrate substrate in multiple ways, including via hydrolysis of linkages between monosaccharide units (Page 7, Lines 15-19). Klock goes on to state the carbohydrate modifying enzyme can be an α-L-fucosidase (Claim 16 of Klock), reading on a glycoside hydrolase.
Klock does not state the glycoside hydrolase, being an α-L-fucosidase, is capable of removing an α-1,2-L-fucose moiety or that the α-L-fucosidase belongs to the glycoside hydrolase family 95 (GH95).
However, Katayama et al. disclose a 1,2-α-L-fucosidase (AfcA), reading on a specific glycoside hydrolase, from Bifidobacterium bifidum belonging to GH family 95 that hydrolyzes terminal α-(1[Wingdings font/0xE0]2)-fucosidic linkages (See entire document, Abstract). α-L-Fucosyl residues are frequently found at the nonreducing termini of various glycoconjugates, including blood group substances, milk oligosaccharides, gastric and submaxillary mucins, and serum glycoproteins (Page 4885, Left Column, Paragraph 1). Recent studies indicate terminal fucosyl residues attached by α-(1[Wingdings font/0xE0]2), α-(1[Wingdings font/0xE0]3) and α-(1[Wingdings font/0xE0]4) linkage play important roles in mammalian cell-to-cell communication mediated through receptor proteins, however, terminal fucose-mediated biological activity is not limited to higher eukaryotic cells but includes bacterial adhesion to host cells as well (Page 4885, Left Column, Paragraph 1). Campylobacter jejuni is known to bind blood group H(O) antigen Fucα(1[Wingdings font/0xE0]2)Galβ(1[Wingdings font/0xE0]4)GlcNAc which facilitates infection of host epithelial cells (Page 4885, Left Column, Paragraph 1). α-L-fucosidase could serve as a powerful tool to elucidate the structure-function relationships of these fucose-containing bioactive glycoconjugates, since it can selectively cleave and remove specific fucosyl residues from the targets without damage (Page 4885, Left Column, Paragraph 2). Katayama et al. state bifidobacteria can be used as key commensals that promote a healthy intestinal tract (Page 4885, Right Column, Paragraph 2). The 1,2-α-L-fucosidase from B. bifidum has substrate specificity for 2’-Fucosyllactose and the blood group H(II) active substance Fucα(1[Wingdings font/0xE0]2)Galβ(1[Wingdings font/0xE0]4)GlcNAc (Page 4889, Left Column and Table 1 of Katayama et al.).
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize the 1,2-α-L-fucosidase from B. bifidum disclosed by Katayama et al. in the method of Klock because Klock specifically states the carbohydrate modifying enzyme can be an α-L-fucosidase and the 1,2-α-L-fucosidase from B. bifidum was a known and effective α-L-fucosidase as taught by Katayama et al. motivated by the desire to prevent C. jejuni infection since the 1,2-α-L-fucosidase can selectively cleave and remove the specific fucosyl residues the C. jejuni uses to bind host cells without damaging the host cell as taught by Katayama et al.
Regarding claim 8, Klock discloses pharmaceutical compositions containing the therapeutic catalyst, being the alpha-L-fucosidase, being in the form of an ingestible capsule (Page 11, Lines 13-24). The therapeutic catalyst being in an ingestible capsule reads on it being encapsulated.
Regarding claim 10, Klock discloses the therapeutic catalyst may be administered orally (Page 11, Lines 13-17). Klock further discloses for oral applications, the therapeutic catalyst can be mixed with a solid to form cores for dragees (Page 12, Lines 15-25), reading on a feed.
Regarding claim 12, Klock discloses the active substance, being the alpha-L-fucosidase, can be in granulate form (Page 13, Lines 4-6).
Claims 1-5, 8, 10, 12 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Klock (WO 1994025061 A1, 11/10/1994) in view of Katayama et al. (Journal of Bacteriology, 08/2004) and Snoeck et al. (Veterinary Microbiology, 2004).
Regarding claims 5 and 18, as discussed above, Katayama et al. disclose the 1,2-α-L-fucosidase from B. bifidum has substrate specificity for the blood group H(II) active substance Fucα(1[Wingdings font/0xE0]2)Galβ(1[Wingdings font/0xE0]4)GlcNAc.
Neither Klock nor Katayama et al. disclose the 1,2-α-L-fucosidase from B. bifidum prevents an intestinal pathogenic infection wherein the pathogen is Escherichia coli expressing F18 fimbriae.
However, Snoeck et al. disclose enterotoxigenic and verotoxigenic F18+ Escherichia coli colonizing the pig small intestine adhere to receptors on intestinal villous enterocytes by F18 fimbriae (See entire document, Abstract). The F18 receptor contains the blood group antigen H-2 (α-fuc-(1-2)-β-Gal-(1-4)-GlcNAc) as the major carbohydrate (Abstract). Snoeck et al. found that incubation with 1% blood group antigen H-2 resulted in inhibition of F18+ E. coli which demonstrates that (α-fuc-(1-2)-β-Gal-(1-4)-GlcNAc) is the main carbohydrate sequence mediating F18 fimbrial binding to villous enterocytes (Page 245, Right Column, Paragraph 1). This finding, being the (α-fuc-(1-2)-β-Gal-(1-4)-GlcNAc) trisaccharide plays a role in the interaction of F18+ E.coli with the intestinal epithelia, leads to a more fundamental understanding of the interaction of fimbrial adhesins with host cell receptors which can enable the improvement of swine production by developing new receptor-based treatments for F18+ E. coli infections (Page 245, Right Column, Paragraph 3).
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize the 1,2-α-L-fucosidase from B. bifidum taught by Katayama et al. in the method of Klock to prevent an intestinal pathogenic infection wherein the pathogen is E. coli expressing F18 fimbriae because Fucα(1[Wingdings font/0xE0]2)Galβ(1[Wingdings font/0xE0]4)GlcNAc is the receptor for E. coli expressing F18 fimbriae as taught by Snoeck et al. and the 1,2-α-L-fucosidase from B. bifidum hydrolyzes terminal α-(1[Wingdings font/0xE0]2)-fucosidic linkages as taught by Katayama et al. Therefore, it would have been obvious to utilize the 1,2-α-L-fucosidase from B. bifidum taught by Katayama et al. to cleave the terminal α-(1[Wingdings font/0xE0]2)-fucosidic linkages and subsequently prevent F18 fimbriae adhesion to the host cell, inhibiting E. coli expressing F18 fimbriae infection because Snoeck et al. state receptor based treatments are needed for improving swine production and the method of Klock is a receptor based method wherein the receptor is modified so binding does not occur.
Claims 1-13 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Klock (WO 1994025061 A1, 11/10/1994) in view of Katayama et al. (Journal of Bacteriology, 08/2004), Snoeck et al. (Veterinary Microbiology, 2004) and Nagy et al. (International Journal of Medical Microbiology, 10/05/2005).
Regarding claim 6, neither Klock, Katayama et al. nor Snoeck et al. disclose administering a direct fed microbial in combination with the alpha-L-fucosidase.
However, Nagy et al. disclose enterotoxigenic Escherichia coli (ETEC) infection is the most common type of colibacillosis of young animals (primarily pigs and calves) and is also a significant cause of diarrhea among travelers and children in the developing world (See entire document, Abstract). The main virulence attributes of ETEC are adhesins and enterotoxins (Abstract). Due to the use of preventative antibiotics being prohibited in the EU, there is a need for antibiotic replacements for treating ETEC infections (Page 450, Right Column, Paragraph 1). Probiotics offer a non-antibiotic approach for the prevention of ETEC diarrhea (Page 450, Left Column, Paragraph 3). Probiotics read on a direct fed microbial.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized a probiotic in the combined method of Klock/Katayama/Snoeck in combination with the alpha-L-fucosidase motivated by the desire to prevent ETEC diarrhea as taught by Nagy et al. because the combined method is drawn to preventing ETEC infection. Thus, it would be obvious to utilize an additional component, being a probiotic, to further prevent infection and the side effects of infection, being diarrhea.
Regarding claim 7, neither Klock, Katayama et al. nor Snoeck et al. disclose administering a direct fed microbial and a protease in combination with the alpha-L-fucosidase.
However, as discussed above, Nagy et al. disclose the main virulence attributes of ETEC are adhesins and enterotoxins (Abstract). Enterotoxins are plasmid-regulated secreted proteins or peptides of ETEC bacteria that act on intestinal epithelium and can be separated into two categories, large-molecular weight heat-labile enterotoxins (LT) and small-molecular weight heat-stable peptide toxins (ST) (Page 446, Left Column, Paragraph 3). A specific ST, STb, is characteristically produced in porcine ETEC, although there have been sporadic cases in men, calves and chickens (Page 447, Left Column, Paragraph 3). STb is sensitive to proteases (Page 447, Right Column, Paragraph 1). Protection of STb from digestion by the addition of protease inhibitors to STb makes it possible to detect its biological function in other animal species (Page 447, Right Column, Paragraph 1).
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized a protease in the combined method of Klock/Katayama/Snoeck in combination with the alpha-L-fucosidase and the probiotic motivated by the desire to digest an enterotoxin, thus preventing its effects, as enterotoxins and adhesins are the main virulence factors of ETEC as taught by Nagy et al. because the combined method is drawn to preventing ETEC infection. Thus, it would be obvious to utilize an additional component, being a protease, to aid in preventing infection.
Regarding claim 9, Klock discloses pharmaceutical compositions containing the therapeutic catalyst, being the alpha-L-fucosidase, being in the form of an ingestible capsule (Page 11, Lines 13-24). The therapeutic catalyst being in an ingestible capsule reads on it being encapsulated.
Regarding claim 11, Klock discloses the therapeutic catalyst may be administered orally (Page 11, Lines 13-17). Klock further discloses for oral applications, the therapeutic catalyst can be mixed with a solid to form cores for dragees (Page 12, Lines 15-25), reading on a feed.
Regarding claim 13, Klock discloses the active substance, being the alpha-L-fucosidase, can be in granulate form (Page 13, Lines 4-6).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-13 and 18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 and 13 of U.S. Patent No. 10933121 B2.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of both the instant application and ‘121 are drawn to administering an effective amount of a glycoside hydrolase capable of removing an alpha-1,2-L-fucose moiety from a pathogen binding site. While the instant claims recite ‘preventing’ and the claims of ‘121 recite ‘treating,’ the method for preventing and treating is the same. Thus, the claims are not patentably distinct from each other because both sets of claims recite the same method. Claim 1 of ‘121 correlates to instant claims 1-3. Claim 2 of ‘121 correlates to instant claim 1. Claim 3 of ‘121 correlates to instant claims 5 and 18. Claim 4 of ‘121 correlates to instant claim 6. Claim 5 of ‘121 correlates to instant claim 7. Claims 6 and 8 of ‘121 correlates to instant claims 10-11. Claims 7 and 10 of ‘121 correlates to instant claims 8-9. Claims 9 and 11 of ‘121 correlates to instant claims 12-13. Claim 13 of ‘121 correlates to instant claim 4.
Thus, the claims of the instant application read on and anticipate the claims of ‘121.
Conclusion
Claims 1-13 and 18 are rejected.
No claims are allowed.
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/A.T.W./Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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