DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Preliminary Amendments
1) Acknowledgment is made of Applicants’ amendments filed 10/01/25, 09/19/25, 10/04/23, 09/04/23 and 05/13/23. The amendment filed 10/01/25 is non-compliant with 37 CFR 1.121 in that the newly submitted claim 75 is underlined. Note that the text of any new claims added by amendment must not be underlined. Further, the status identifier indicated for claims drawn to non-elected species and claim(s) covering elected species (for example, claim 14) is incorrect. Appropriate correction is needed.
Election
2) Acknowledgment is made of Applicants’ elections filed 10/01/25 and 09/19/25 in response to the restriction and species election requirement mailed 05/19/25. Applicants have elected, without traverse, invention I and the Lactobacillus and L. reuteri DSM20016 recombinant probiotic bacterium species, and the GbpA species or homologue thereof in combination with a bacterial surface protein, and the Gammaproteobacteria GbpA source species within the elected invention I.
Status of Claims
3) Claims 11, 14, 47, 48, 50, 59, 61, 62 and 65 have been amended via the preliminary amendment filed 5/13/23.
Claims 2-4, 7-10, 12-13, 17-46, 49, 51, 53-58, 60, 63, 64 and 66-69 and have been canceled via the preliminary amendment filed 5/13/23.
New claims 70-74 have been added via the preliminary amendment filed 5/13/23.
Claims 1, 11, 15, 48 and 50 have been amended via the amendment filed 10/01/25.
New claim 75 has been added via the amendment filed 10/01/25.
Claims 5, 6, 52, 59, 61, 62, 65 and 71-74 are withdrawn from consideration as being directed to a non-elected invention or species. See 37 CFR 1.142(b) and M.P.E.P § 821.03.
Claims 1, 5, 6, 11, 14-16, 47, 48, 50, 52, 59, 61, 62, 65 and 70-75 are pending.
Claims 1, 11, 14-16, 47, 48, 50, 70 and 75 are examined on the merits.
Drawings
4) Acknowledgment is made of Applicants’ drawings filed 09/04/23, which are non-compliant under 37 CFR 1.121 in that the post-filing drawings are not properly identified. 37 CFR 1.121(d) requires that the drawings are properly identified in the top margin, for example, as “Replacement Sheet”, “New Sheet”, or “Annotated Sheet” whichever is appropriate.
Sequence Listing
5) Acknowledgment is made of Applicants’ sequence listing which has been entered on 10/04/23.
Substitute Specification
6) Acknowledgment is made of Applicants’ substitute specification filed 10/04/23.
Priority
7) The instant AIA application filed 05/13/23 is a continuation-in-part of U.S. application 16486803 filed 08/16/2019, now US patent 11684643, which is the national stage 371 application of PCT/CA2018/050188 filed 02/19/2018, which claims priority to the provisional application 62/460,185 filed 02/17/2017.
Objection(s) to Specification
8) The instant specification is objected to for the following reasons:
(a) The first paragraph of the specification does not accurately reflect the issued status of the prior application, as indicated above in italicized letters under ‘Priority’.
(b) The amended paragraphs [0166], [0169], [0171], [0172], [0173], [0174], [0175], [0176], [0177], [0189], [0190], [0191], [0192], [0197], [0198] and [0199] are objected to for referring to “continuation of Figure ....B-1 and the second portion” of the same numbered Figure. For example, “Figure 36B-2” being “a continuation of Figure 36B-1 and the second portion of” the same Figure number, i.e., “Figure 36B”. For clarity, it is suggested that Applicants present paragraphs [0194] to [0196] as one paragraph as indicated below:
--[0194] Figures 36B-1 to 36B-3 represent the nucleic acid sequence of the pAH162-ttrACBSR vector (SEQ ID NO: 46).--
Analogous amendments are suggested to other identified paragraphs.
(c) The amended paragraphs [0165], [0166], [0168], [0169], [0171], [0173], [0176], [0189], [0191], [0194] and [0197] are objected to for the confusing descriptions. For example, “Figure 32C-1” being a first portion and “Figure 32C-2” being a continuation of the same numbered Figure, i.e., “Figure 32C”. For clarity, it is suggested that Applicants present paragraphs [0165] to [0166] as one paragraph as indicated below:
--[0165] Figures 36C-1 to 36C-2 represent the nucleic acid sequence encoding a mucus binding protein (MBP), (SEQ ID NO: 53).—
Analogous amendments are suggested to other identified paragraphs.
(d) The amended paragraph [0171] refers to SEQ ID NO: 30 and states that “the GbpA fragment” therein is “underlined” in Figure 33C-1. However, the drawing for FIGURE 33C-1 filed 09/04/23 does not include any underlining.
Rejection(s) under 35 U.S.C § 112(a) or (pre-AIA ), First Paragraph
9) The following is a quotation 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 35 U.S.C § 112 (pre-AIA ), first paragraph:
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 the invention.
10) Claims 1, 11, 14-16, 47, 48, 50, 70 and 75 are rejected under 35 U.S.C § 112(a) as containing 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
The purpose of the written description requirement is “to ensure that the inventor had possession, as of the filing date of the application relied on, of the specific subject matter later claimed by him.” In re Edwards, 568 F.2d 1349, 1351-52, 196 USPQ 465, 467 (CCPA 1978). The analysis of whether the as-filed specification complies with the written description requirements calls for the Office to compare the scope of the claims with the scope of the description to determine whether Applicants have demonstrated possession of the full scope of the claimed invention at the time of the invention. An analysis of the breadth of the claims is set forth below.
Claim 1 is representative of the instant invention, and it is drawn to a recombinant probiotic bacterium expressing an N-acetyl glucosamine binding protein A or homologue thereof co-expressed or recombined with a bacterial surface protein. While the N-acetyl glucosamine binding protein A of the dependent new claim 75 comprises an amino acid sequence having at least 45% sequence identity to the amino acid sequence set forth in SEQ ID NO: 29, ‘an N-acetyl glucosamine binding protein A or homologue thereof’ recited in claim 1 and encompassed within claims 14-16, 47, 48, 50 and 70 represents a huge genus of divergent structure encompassing variants, isoforms, analog, truncates, homologs and mutants of unlimited structure, size/length and source. The N-acetyl glucosamine binding protein A recited in claim 11 is from the class Gammaproteobacteria, which also represents a very large genus of divergent structure encompassing variants, isoforms, analog, truncates, homologs and mutants of unlimited structure and size/length of antigenically and genetically diverse members of the class Gammaproteobacteria. The amino acid sequence at least 45% identical to SEQ ID NO: 29 is up to 55% non-identical thereto and therefore represents a large genus encompassing sequence and homologue species having random substitutions, additions, deletions, insertions and other mutations or a combination thereof anywhere along the entire length of SEQ ID NO: 29. Similar analysis applies to the limitation ‘a bacterial surface protein’ and ‘a mucus binding protein’ and ‘a fragment’ thereof of incredibly broad scope. Said structurally diverse variant, mutant, homolog, isoform, truncated and analog species are required to retain their N-acetyl-glucosamine binding and mucus binding biologic functions respectively. The claimed recombinant probiotic bacterium co-expressing said genus of N-acetyl glucosamine binding protein A genus or its homologue genus and said bacterial surface protein genus and said mucus binding protein genus is presented as a probiotic composition in a pharmaceutically acceptable carrier. See for example, claim 70. The claimed probiotic bacterium is intended for use in a method of reducing inflammation in the GI tract of a human subject and in a method of treating or preventing inflammatory bowel disease as is evident from claims 65 and 62. The claimed probiotic composition is intended for use in a method of ameliorating gastrointestinal inflammation including one associated with inflammatory bowel disease in a human subject in need thereof as is evident from claims 71-73. Thus, the variant and homologue species identified supra and comprised in the claimed probiotic bacterium and the claimed probiotic composition are required to have the above-identified requisite therapeutic and prophylactic functions in a human subject. In order to satisfy the written description provision of 35 U.S.C § 112(a), a representative number and variety of these species of highly variable structure are required to be correlated with the requisite functions. However, at the time of the invention, Applicants were not in possession of a representative number and variety of species within the broad variant genus each expressed by the claimed recombinant probiotic bacterium and each having the requisite therapeutic and prophylactic functions correlated with the variable structure, and the full scope of the invention as claimed.
Sufficient description to show possession of a genus may be achieved by means of disclosure of a representative number of structurally variable N-acetyl glucosamine binding protein A species or its homologue species and structurally variable bacterial surface protein species and structurally variable mucus binding protein species and fragment species, defined by structure or sequences falling within the scope of the variable genus, each co-expressed by a recombinant probiotic bacterium including Lactobacillus species, or by recitation of structural features common to members of the variable genus, which features constitute a substantial portion of the genus. Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. The structure of a representative number and variety of species must be correlated with the requisite and the intended functional characteristic(s). Possession may not be shown by merely mentioning the claimed genus or how to identify their common structural features. The written description requirement can be met by describing the claimed subject matter to a person skilled in the art using sufficiently detailed, relevant identifying characteristics such as functional characteristics, and correlating those functional characteristics with a disclosed structure. See Enzo Biochem v. Gen-Probe, 323 F.3d 956, 964, 967, 968 (Fed. Cir. 2002). MPEP § 2163.02 states, ‘[a]n objective standard for determining compliance with the written description requirement is, ‘does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed’. The courts have decided:
The purpose of the “written description” requirement is broader than to merely explain how to “make and use”; the applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for the purposes of the “written description” inquiry, whatever is now claimed.
See Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991). The written description provision of 35 U.S.C § 112(a) is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
In the instant case, there is a lack of showing of a concrete structure-function correlation for a sufficient number and variety of the two elements co-expressed by the claimed probiotic bacterium. For instance, a concrete structure-function correlation is lacking for up to 55% non-identical N-acetyl glucosamine binding protein A variant species and homologue species representative of the entire large genus. The exact positions within the sequence of SEQ ID NO: 29 that tolerate substitutions, insertions, deletions, additions and other modifications and still retain the N-acetyl glucosamine binding function and which when co-expressed by a recombinant probiotic bacterium recombined with structurally divergent bacterial surface protein species or structurally divergent mucus binding protein (MBP) species or MBP fragment species would have the intended gastrointestinal inflammation-ameliorating, the irritable bowel disease-ameliorating functions, the inflammatory bowel disease-treating, or the inflammatory bowel disease-preventing therapeutic and prophylactic functions are not identified. The one or more specific regions, linear and/or conformational domains or epitopes of the N-acetyl glucosamine binding protein A, of the bacterial surface protein, and of the mucus binding protein that are responsible for or that are correlated with said therapeutic and prophylactic functions have not been identified such that one of skill in the art would immediately envision or recognize at least a substantial number of members of the broadly recited variant, homolgue and fragment genus having those functions. To fulfill the written description requirements set forth under 35 U.S.C § 112(a), the specification must describe at least a substantial number of members of the claimed genus, or alternatively describe a representative member of the claimed genus, which shares a particularly defining feature common to at least a substantial number of the members of the claimed genus, which would enable the skilled artisan to immediately recognize and distinguish its members from others, so as to reasonably convey to the skilled artisan that Applicants have possession of the full scope of the claimed invention. 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’ (at 1106). A ‘representative number of species’ means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus as in the instant case, one must describe a sufficient variety of species to reflect the variation within the genus, with their structure correlated with the requisite functions. Other than the recombinantly co-expressed GbpA-MBP chimeric protein of the amino acid sequence of SEQ ID NO: 29, Applicants were not in possession of the recombined or coexpressed species encompassed within the huge genus. However, the disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) (“[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated”). From Applicants’ specification, a skilled artisan cannot immediately envision or recognize at least a substantial number and variety of variant and homologue members of the broadly claimed genus of the N-acetyl glucosamine binding protein A and homologues thereof, the genus of the bacterial surface protein, and the genus of mucus binding protein and fragments thereof, each having the above-identified functions. A convincing structure-function relationship must exist, which is lacking. ‘A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when ..... the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.’ In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004). Skilled artisans would not have known which GbpA variant and homologue species and which mucus binding fragment species would have the requisite binding functions and the gastrointestinal inflammation-ameliorating and the irritable bowel disease-ameliorating functions, and the inflammatory bowel disease-treating and the inflammatory bowel disease-preventing therapeutic and prophylactic functions without empirically testing each variant and homologue species and each fragment species. This is important because the art reflects unpredictability as to which amino acids in a specific protein or a polypeptide sequence can be varied without adversely affecting the functional properties of that specific protein or polypeptide sequence. While it is known in the art that variation in one or more amino acids is possible in a given protein or sequence, the exact position within its amino acid sequence where replacements or variations can be made, with a reasonable expectation of success of retaining the protein’s or polypeptide sequence’s functional integrity or competence, is not certain or predictable. A random replacement affecting specific amino acid positions that are critical, for example, to the three-dimensional conformational structure and to a specific property of the protein or polypeptide, would result in a protein or polypeptide that may be non-functional, or not optimally functional, because such positions tolerate no or little modifications. With regard to the functional unpredictability of bacterial polypeptides, the prior art recognized that the existence of at least 95%, or even 98% sequence identity between two bacterial polypeptides is not necessarily predictive of identical or near identical functional activity. For example, the prior art documented that two bacterial polypeptide which are 98% identical to each other are functionally different. See title; abstract; and the last sentence of paragraph bridging pages 2405 and 2406 of Seffernick et al. J. Bacteriol. 183: 2405-2410, 2001. This art-recognized functional unpredictability combined with the lack of adequate description and lack of structure-function correlation for the full breadth of the variant or homologue genus and the fragment genus in the instant case points to the unpredictability factor under the written description provision. Note that predictability of the aspect at issue is one of the multiple factors to consider under written description analysis. Capon v. Eshhar (CAFC 2005). With regard to proteins in general, Skolnick et al. (Trends in Biotechnology 18: 34-39, 2000) taught that a skilled artisan is well aware that assigning functional activities for any particular protein or a family of proteins based upon sequence homology is inaccurate, partly because of the multifunctional nature of proteins. See abstract; and page 34. Even in situations where there is some confidence of a similar overall structure between two proteins, only experimental research can confirm the artisan’s best guess as to the function of the structurally related protein. See abstract and Box 2. With regard to the structure-function relationship of an encoded amino acid sequence in general, Rudinger J. (In: Peptide Hormones. (Ed) JA Parsons, University Park Press, pages 1-7, 1976) taught that ‘the significance of particular amino acid sequences for different aspects of biological activity cannot be predicted a priori but must be determined from case to case by painstaking experimental study’. See page 6 of Rudinger. Rudinger further taught that ‘it is impossible to attach a unique significance to any residue in a sequence’ and that a ‘given amino acid will not by any means have the same significance in different peptide sequences, or even in different positions of the same sequence. See page 3 of Rudinger. Lazar et al. (Mol. Cellular Biol. 8: 1247-1252, 1988) demonstrated that a substitution of Leu with a conservative amino acid residue, such as, Ile or His, in the transforming growth factor (TGF) alpha led to a mutant protein with dramatically altered biological activities. Lazar et al. stated that they ‘did not expect that a mutation of Leu to Ile (which have similar sizes and polarities) would cause such a strong effect’. See paragraph bridging left and right columns on page 1251; and third full paragraph on page 1251.
In sum, the references of Seffernick et al., Skolnick et al., Rudinger J., and Lazar et al. document the functional unpredictability of variant or homologue protein sequences as recognized in the state of the art at the time of the invention. In the instant case, at the time of the invention, the effect of variations on preservation of the N-acetyl-glucosamine binding function, the mucus binding function, and the therapeutic and prophylactic functions of the co-expressed elements was not predictable. For example, Applicants have not described the claimed genus of up to 55% non-identical species of SEQ ID NO: 29, the GbpA homologue species, the bacterial surface protein species, the mucus binding protein species and its fragment species, each correlated with the requisite and the intended functions, such that the specification might reasonably convey to the skilled artisan that Applicants had possession of the variant genus, the homologue genus, the bacterial surface protein genus, the mucus binding protein genus and its fragment genus, and the full scope of claimed invention at the time the application was filed. The lack of evidence and the lack of adequate written description within the as-filed specification for the broad genus of variable structure and for the entire scope of the instantly claimed invention when weighed with the state-of-the-art teachings set forth supra clearly establish a lack of structure-function correlation for a representative number and variety of species encompassed within each of the varied genus.
The written description inquiry is case and context-specific. It “depend[s] on the nature of the claimed invention and the knowledge of one skilled in the art at the time an invention is made and a patent application is filed.” Ariad, 560 at 1372. A number of factors guide the inquiry, including “the existing knowledge in the particular field, the extent and content of the prior art, the maturity of the science or technology, and the predictability of the aspect at issue.” Ariad, 560 at 1372 [Emphasis added]. According to MPEP 2163:
The description needed to satisfy the requirements of …… 35 U.S.C § 112 “varies with the nature and scope of the invention at issue, and with the scientific and technologic knowledge already in existence.” Capon v. Eshhar, 418 F.3d at 1357, 76 USPQ2d at 1084. Patents and printed publications in the art should be relied upon to determine whether an art is mature and what the level of knowledge and skill is in the art.
In the instant case, encompassed within the scope of the huge genus are numerous structural variants, mutants, homologs, isoforms, analogs, fragments, and truncated species. The specification does not describe sufficient members representative of the claimed genus by complete structure along with a correlation to the requisite functions. At the time of the invention, despite the high level of skill in the art of biotechnology or biochemistry, one could not have predicted the specific binding functions and the identified therapeutic and prophylactic functions of the species encompassed within the huge genus. One of skill in the art would not reasonably conclude that the disclosure provides a representative number and variety of species to describe the widely structurally divergent genus. The instant specification does not describe the claimed invention in sufficient detail to convey to a person skilled in the art that Applicants were in possession of variant genus and the full scope of the claimed invention at the time of filing. The written description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-373 (Fed. Cir. 1984) (affirming rejection because the specification does ‘little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.’). The essence of the written description requirement is that a patent applicant, as part of the bargain with the public, must describe his or her invention so that the public will know what it is and that he or she has truly made the claimed invention. See Festo Corp. v. Shoketsu Kinzoku Kogyo Kabushiki Co., 535 U.S. 722, 736 (2002) (“The requirements must be satisfied before issuance of the patent, for exclusive patent rights are given in exchange for disclosing the invention to the public. What is claimed by the patent application must be the same as what is disclosed in the specification . . . .” (internal citations omitted)); O’Reilly v. Morse, 56 U.S. 62, 120–21 (1853) (“The evil is the same if he claims more than he has invented, although no other person has invented it before him. He prevents others from attempting to improve upon the manner and process which he has described in his specification and may deter the public from using it.”). We have explained that “requiring a written description of the invention plays a vital role in curtailing claims . . . that have not been invented, and thus cannot be described.” Ariad, 598 F.3d at 1352. “For generic claims, we have set forth a number of factors for evaluating the adequacy of the disclosure, including ‘the existing knowledge in the particular field, the extent and content of the prior art, the maturity of the science or technology, [and] the predictability of the aspect at issue.” Id. (quoting Capon v. Eshhar, 418 F.3d 1349, 1359 (Fed. Cir. 2005)). For the reasons delineated supra, one skilled in the art would not recognize from the as-filed disclosure that Applicants were in possession of the broad variant and homologue genus, the MBP protein genus, and the MBP fragment genus, and the full scope of the invention as claimed at the time the application was filed. Instant claims do not meet the written description provision of 35 U.S.C § 112(a) or (pre-AIA ) first paragraph.
Rejection(s) under 35 U.S.C § 112(b) or (pre-AIA ) Second Paragraph
11) 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.
12) Claims 1, 11, 14-16, 47, 48, 50, 70 and 75 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 inventor or a joint inventor, or for the pre-AIA the Applicants regard as the invention.
(a) Claim 1 is ambiguous and indefinite in the limitation “a homologue thereof”, because it is unclear what does this limitation represent or encompass structure-wise and scope-wise. Does it encompass variants, truncates, mutants etc of N-acetyl-glucosamine binding protein A of any generic structure, source, length and/or size? In the absence of a precise structure, one of ordinary skill in the art cannot understand in an unambiguous way the subject matter that is being claimed and the scope of the claim. The claim fails to distinctly claim the subject matter. Note that each claim must be definite and complete in and of itself.
(b) The dependent claim 14 is indefinite for lacking sufficient antecedence in the limitation “fragment thereof”. For proper antecedence, it is suggested that Applicants replace the above-identified limitation with the limitation --the fragment thereof--.
(c) Claim 15 is indefinite for having improper antecedence in the limitation “the” bacterial surface protein A. Claim 15 depends from claim 1, which does not recite a bacterial surface protein A.
(d) Claims 11, 14-16, 47, 48, 50, 70 and 75, which depend directly or indirectly from the amended claim 1, are also rejected as being indefinite due to the indefiniteness identified above in the base claim(s).
Notice Re Prior Art Available under Both Pre-AIA and AIA
In the event the determination of the status of the application as subject to AIA 35 U.S.C § 102 and § 103 (or as subject to pre-AIA 35 U.S.C § 102 and § 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection would be the same under either status.
Rejection(s) under 35 U.S.C § 102
13) The following is a quotation of the appropriate paragraphs of 35 U.S.C § 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
14) Claims 1, 11, 14-16, 14-16, 47, 48, 70 and 75 are rejected under 35 U.S.C § 102(a)(2) as being anticipated by WO 2018051223 A1 (WO ‘223, filed 09/13/2016).
WO ‘223 disclosed a recombinant, genetically modified Lactobacillus reuteri probiotic bacterium expressing a fusion (recombined) protein comprising an amino acid sequence having at least 45% sequence identity to the amino acid sequence set forth in Applicants’ SEQ ID NO: 29. A recombinant Lactococcus lactis probiotic bacterium comprising a chromosomally integrated cell adherence polypeptide linked to a mucus-binding polypeptide is taught. The prior art amino acid sequence of SEQ ID NO: 10 is at least 45% identical to the instantly recited SEQ ID NO: 29 and comprises therein a lengthy amino acid sequence of a mucus binding protein such as a sequence from within Applicants’ SEQ ID NO: 21 or SEQ ID NO: 28 fused (recombined) with an amino acid sequence homologue comprising therein the NPA and TLT sequences of Applicants’ V. cholerae (Gammaproteobacteria) GbpA protein of SEQ ID NO: 19. A pharmaceutical composition comprising said genetically modified Lactobacillus reuteri probiotic bacterium with a pharmaceutically acceptable carrier is taught. See sections [006] to [008], [0031] and [0051]; and pages 14 and 54; and the sequence alignment set forth below with the NPA and TLT GbpA sequences underlined.
Claims 1, 11, 14-16, 14-16, 47, 48, 70 and 75 are anticipated by WO 2018051223 A1.
Rejection(s) under 35 U.S.C § 103
15) 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 of this title, 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 claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 148 USPQ 459, that are applied 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 unobviousness.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C § 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 36 C.F.R 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C § 103(c) and potential 35 U.S.C § 102(e), (f) or (g) prior art under 35 U.S.C § 102(a).
16) Claim 50 is rejected under 35 U.S.C § 103 as being unptatentable over WO 2018051223 A1 (WO ‘223) as applied to claim 1 above and further in view of WO 2016/102660 A1.
The disclosure of WO ‘223 is set forth supra, which is silent on the recombinant Lactobacillus reuteri being Lactobacillus reuteri DSM20016.
However, Lactobacillus reuteri DSM20016 was an alternative recombinant Lactobacillus reuteri probiotic strain that was known in the art at the time of the invention for recombinant transformation to express a protein. For example, see page 15 including the 3rd full paragraph therein of WO 2016/102660 A1.
Given the teachings of WO 2016/102660 A1, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use WO 2016/102660 A1’s alternative, art-known Lactobacillus reuteri DSM20016 in place of the Lactobacillus reuteri of WO ‘223, the very same strain used by Applicants and the very same strain recited in instant claim 50 to produce the instant invention. Substitution of one Lactococcus reuteri with another, alternative, art-known recombinant Lactococcus reuteri would have been well within the realm of routine experimentation, would have been obvious to a skilled artisan, and would have brought about similar predictable results or effects absent evidence to the contrary. It is obvious to substitute known elements one for another if it will no more than yield predictable results. MPEP 2143 (I)(B) and KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007). To those of ordinary skill in an art, it is generally obvious to replace a known product by substituting a known equivalent for one of its components. See e.g., Hotchkiss v. Greenwood, 52 U.S. 248 (1850) (substitution of porcelain door knob in known process of making metal or wood door knobs held obvious); In re Mayne, 104 F.3d 1339, 1340 (Fed. Cir. 1997) (‘Because the applicants merely substituted one element known in the art for a known equivalent, this court affirms [the rejection for obviousness’]). As set forth in KSR Int'l Co. v. Teleflex Inc., 27 S. Ct. 1727, 1741-42, 82 USPQ2d 1385, 1397 (2007), [i]n determining whether the subject matter of a patent claim is obvious, neither the particular motivation nor the avowed purpose of the patentee controls. What matters is the objective reach of the claim. If the claim extends to what is obvious, it is invalid under § 103". Furthermore, ("[T]he law does not require that the references be combined for the reasons contemplated by the inventor"). See In re Beattie, 974 F.2d 1309, 1312, 24 USPQ2d 1040, 1042 (Fed. Cir. 1992). The KSR decision sets forth “if a technique has been used to improve one device, and a person of skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond that person’s skill”.
Claim 50 is prima facie obvious over the prior art of record.
Relevant Art
17) The art made of record and not relied upon in any of the rejections is considered pertinent to Applicants’ disclosure:
t Kandler et al. (Zentralbl. Bakteriol. Parasitenkd. Infektionskr. Hyg., I Abt., Orig. C1: 264-269, 1980, English Abstract) reported the isolation of Lactobacillus reuteri DSM20016 from faeces. See Abstract.
Conclusion
18) No claims are allowed.
Correspondence
19) Any inquiry concerning this communication or earlier communications from the Examiner should be directed to S. Devi, Ph.D., whose telephone number is (571) 272-0854. A message may be left on the Examiner’s voice mail system. The Examiner is on a flexible work schedule, however she can normally be reached Monday to Friday from 7.00 a.m. to 4.00 p.m. (EST). If attempts to reach the Examiner by telephone are unsuccessful, the Acting Supervisor, Vanessa Ford, can be reached at (571) 272-0857. The fax phone number for the organization where this application or proceeding is assigned (571) 273-8300.
20) Information regarding the status of an application may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center or Private PAIR to authorized users only. Should you have questions about access to Patent Center or the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, Applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
/S. DEVI/
S. Devi, Ph.D.Primary Examiner
Art Unit 1645
November, 2025
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