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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/10/2025 is in compliance with the provisions of 37 C.F.R. 1.97. All references cited in this IDS have been fully considered.
Election/Restrictions
The present application remains examined per applicant’s election without traverse of Group I in the reply filed on 05/27/2025.
Claim 127 remains withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Additionally, the application remains examined per applicant’s election of a composition comprising a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 75.
Claims 110-112, 116-117, 124-126, and 128-138 are directed to the elected invention and have been examined in accordance with the species election.
Amendments
Claim 110 now requires suppressing colonization in a subject in need thereof by inhibiting replication and/or survival of the pathogenic bacterium.
Claim 123 is canceled.
Claim 128 now requires treating a disease or disorder associated with colonization by a bacterium belonging to the species Klebsiella pneumoniae in a subject in need thereof by inhibiting replication or survival of the bacterium belonging to the species Klebsiella pneumoniae.
Claim 130 now requires suppressing colonization by inhibiting replication and/or survival of the oral microbiome bacterium.
Drawings
Previous objection to the drawings
Figs. 1B-1E, 5A-5D, 6, 12B, 30, and 33 were objected to for minor informalities. Applicant has made the appropriate corrections. Accordingly, the objection to the drawings is withdrawn and the amended drawings are accepted.
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.
Previous rejections under 35 U.S.C. § 112
RE: Rejection of claims 110-112, 116-117, and 123-138 under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention.
Applicant traverses the rejection of record by arguing that “[t]he independent claims recite ‘suppressing colonization by a pathogenic bacterium belonging to the species Klebsiella pneumoniae’ and the specification defines “suppressing” as any form of inhibiting an undesired bacterium (Remarks, p. 10, par. 1). Moreover, applicant argues that the specification provides data showing effective inhibition of Klebsiella pneumoniae growth and replication by bacterial strains corresponding to the recited strains and the specification further describes criteria by which a person having ordinary skill in the art may conclude suppression of colonization (Remarks, p. 10, par. 2).
Applicant’s arguments have been fully considered and are sufficient to overcome the rejection of record. Upon reconsideration of the definiteness standard, applicant’s claims recite a function and a require an effective amount. In light of applicant’s special definitions for “suppressing” and “treating”, the phrase “effective amount” is definite.
For at least these reasons, the rejection under 35 U.S.C. § 112(b) is withdrawn.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an 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.
Previous rejection under 35 U.S.C. § 102
RE: Rejection of claims 110 and 123-126 under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Borody et al. (WO 2017/075098), as evidenced by Mysara et al. (FEMS Microbiology Ecology, 2017, Vol. 93, pages 1-12).
Applicant traverses the rejection over Borody by arguing the following.
First, applicant argues that Borody does not anticipate the claim because it lists K. pneumoniae among a myriad list of disorders with no apparent unifying features (Remarks, p. 11, par. 4). To substantiate this argument, applicant submits a Rule 132 declaration by Dr. Gregory Medlock, a scientist employed by applicant. Dr. Medlock’s declaration states that Borody only mentions K. pneumonia treatment in two paragraphs ([0045] and [0097]) among other disorders not relating to K. pneumonia (Declaration, par. 11 and 12). Dr. Medlock continues by arguing that although Borody may teach treatment of pathogens, such as Clostridioides difficile, this microorganism is disparate from K. pneumonia and Borody’s results do not make it more plausible that the bacteria it names would also be effective in inhibiting K. pneumoniae replication or survival (Declaration, par. 13).
Second, applicant argues that Fusobacterium mortiferum (the elected species) is mentioned only in a list of bacterial species in paragraphs [0057], [0058], [0131], [0148], and [0149] and F. nucleatum was previously shown to enhance rather than inhibit K. pneumoniae growth (Declaration, par. 14). Declarant continues by arguing that several species taught by Borody did not have effect on K. pneumoniae and this therefore makes it “difficult to believe that any given bacterium from this list could inhibit K. pneumoniae replication or survival” and “certainly [Declarant] could expect to fail with at least some of these options, and even to worsen the problem by attempting to use F. nucleatum” (Declaration, par. 14). Declarant argues that there is nothing specific to F. mortiferum in Borody’s list of bacteria or elsewhere that makes it more plausible that another Fusobacterium strain having a 16S rRNA gene sequence recited in (vii) would be effective in inhibiting K. pneumoniae replication or survival and because other species of Fusobacterium had been shown to enhance survival of K. pneumoniae, Declarant would have expected F. mortiferum to enhance rather than inhibit K. pneumoniae replication or survival (Declaration, par. 15-16).
Applicant’s arguments and the Declaration submitted by Dr. Gregory Medlock have been fully considered but are not sufficient to overcome the rejection of record for anticipation.
When the species is clearly named, the species claim is anticipated no matter how many other species are additionally named (MPEP § 2131.02(II)). Although the Examiner acknowledges that Borody teaches a litany of disorders and a number of bacterial species which may treat said disorders, the fact that Borody teaches F. mortiferum as an acceptable bacterium to treat K. pneumoniae infection is sufficient to sustain the rejection for anticipation. And although applicant may have observed that other species taught by Borody are not capable of treating K. pneumoniae infection, the expected result based upon this disclosure is that the species would be capable of such an effect. Observing that other species (such as F. nucleatum, C. aerofaciens, C. comes, and E. hallii) are not capable of inhibiting K. pneumoniae may be an indication of non-obviousness for a claim to methods of using the other species for promoting growth of K. pneumoniae but those observations cannot be applied to a determination of anticipation (or obviousness) for applications of F. mortiferum. In other words, Borody’s direct teachings cannot be entirely disregarded simply because other species do not behave the way that Borody describes and applicant has not provided any evidence that F. mortiferum was considered to be incapable of such an effect prior to the effective filing date.
Moreover, Declarant argues that Borody improperly lists a litany of potentially treatable microorganisms based upon an observation that C. difficile infection can be treated (see “’bacterial pathogens’ are not monolithic”; Declaration, par. 13). It is noted that applicant’s specification draws these same conclusions by specifically calling out C. difficile as a pathogenic microorganism which can be suppressed by administering “a therapeutically effective amount of any of the foregoing compositions” (Specification, p. 9, lines 5-11)(the “forgoing compositions” including a litany of alternatively useable species including bacteria which applicant also argues are not capable of inhibiting K. pneumoniae) and by teaching that the methods of treating a disease or disorder associated with bacterial colonization include treatment of Vancomycin Resistant Enterococci (VRE), Carbapenem Resistant Enterobacteriaceae (CRE), Neisseria gonorrheae, Multidrug Resistant Acinetobacter, Campylobacter, Extended spectrum beta-lactamase (ESBL) producing Enterobacteriaceae, Multidrug Resistant Pseudomonas aeruginosa, Salmonella, Drug resistant non-typhoid Salmonella, Drug resistant Salmonella Typhi, Drug resistant Shigella, Methicillin Resistant Staphylococcus aureus, Drug resistant Streptococcus pneumoniae, Drug resistant Tuberculosis, Vancomycin resistant Staphylococcus aureus, Erythromycin Resistant Group A Streptococcus, Clindamycin resistant Group B Streptococcus, Clostridium difficile, multi-drug resistant Klebsiella pneumoniae, carbapenem-resistant Klebsiella pneumoniae, Klebsiella pneumoniae strain BAA-2552, Klebsiella pneumoniae strain KP-1, Klebsiella pneumoniae strain 700721, Klebsiella pneumoniae strain 13882, Klebsiella pneumoniae strain 34El, Klebsiella pneumoniae strain BAA-1705, Klebsiella pneumoniae strain 700603, or Klebsiella pneumoniae strain Kp-2H7 (Specification, p. 11, lines 11-24; p. 13, lines 17-29). Applicant’s working examples are only directed to CRE and VRE and therefore the disclosure appears to have made the same logical conclusions which applicant asserts to be improper in Borody.
For at least these reasons, the rejection of record is proper and must be maintained. In order to address the newly added claim language, the rejection has been maintained but modified. The thrust of the rejection has not changed.
Maintained but modified rejection under 35 U.S.C. § 102
Claims 110 and 124-126 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Borody et al. (WO 2017/075098), as evidenced by Mysara et al. (FEMS Microbiology Ecology, 2017, Vol. 93, pages 1-12).
Borody et al. (hereinafter Borody) teaches pharmaceutical compositions and methods suitable for the treatment of diseases in mammals [0001]. More specifically, Borody discloses the treatment of various diseases such as gastrointestinal diseases in humans using fecal microbiota-related therapy (Id.). Borody teaches that mammals harbor diverse microbial species in their gastrointestinal (GI) tracts and a healthy microbiota provides the host with benefits including colonization resistance to a broad spectrum of pathogens, nutrient biosynthesis, and immune stimulation that maintains a healthy gut epithelium and systemic immunity ([0002]).
Regarding claim 110, Borody teaches a method for treating a disorder selected from a group consisting of carbapenem-resistant Klebsiella pneumoniae (i.e., a pathogenic bacterium belonging to the species Klebsiella pneumoniae)([0045]). Borody’s therapeutic composition comprises at least one fecal microorganism selected from a group which comprises F. mortiferum. Although Borody does not teach the 16S rDNA sequence having at least 97% sequence identity to the nucleotide sequence of SEQ ID NO: 75, the teaching of F. mortiferum is sufficient to meet the claim because SEQ ID NO: 75 corresponds to the bacterium F. mortiferum and every species of F. mortiferum would be expected to inherently possess at least 97% sequence identity to the nucleotide sequence of SEQ ID NO: 75. Mysara provides evidence that all species of F. mortiferum inherently possess greater than 97% identity to SEQ ID NO: 75 by teaching that during OTU clustering, groups having sequence similarity are clustered together and the most common cut-off for this is 97% (p. 10, left col., par. 1). This threshold is selected for practical reasons because it offers a compromise between potential inflation due to sequencing errors and a cut-off used for taxonomic classification (Id.). Additionally, Mysara teaches that 97% is commonly used as a threshold for delineating bacterial species and for taxonomic families consisting of species showing high evolutionary conservation, the cut-off will be more stringent than 97% (abstract). Accordingly, the “97%” threshold is a conservative value and therefore Borody’s F. mortiferum would have been reasonably expected to have “at least 97% sequence identity to the nucleotide sequence of SEQ ID NO: 75” as claimed.
Borody’s methods involve the administration of an effective amount of a therapeutic composition ([0050]) and Borody teaches administering a subject a “pharmaceutically effective dose” of a therapeutic composition comprising live non-pathogenic bacteria ([0032]). Borody’s teachings of “effective amounts” and “pharmaceutically effective doses” are considered to be synonymous with the phrase therapeutically effective amount. This interpretation is supported by applicant’s definition of the phrase which states that “therapeutically effective amount may be used interchangeably with the term ‘effective amount’” (p. 71, lines 22-27).
As such, Borody’s methods differ only in that they do not explicitly teach that the method is for suppressing colonization. Nonetheless, Borody’s method of treating Klebsiella pneumoniae is equivalent to the instantly recited method of “suppressing colonization”. This interpretation is consistent with applicant’s definition for the term “suppressing” which refers to “any form of inhibiting an undesired bacteria” (p. 64, lines 5-7). Moreover, because Borody teaches that the composition can treat K. pneumoniae, it is considered to also teach that the treatment is by inhibiting replication and/or survival of the pathogenic bacterium. And even if Borody does not imply such an effect, "the discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." and (MPEP § 2112(I); emphasis added).
Thus, Borody, as evidenced by Mysara, teaches claim 110.
Regarding claim 124, Borody teaches that the composition is a “therapeutic composition” and can be provided together with a pharmaceutically acceptable carrier such as an excipient in order to permit the formation of a pharmaceutical composition ([0072]).
Regarding claim 125, Borody teaches that the composition can be formulated as an enteric coated capsule, an enteric coated microcapsule, or formulated as part of or administered together with food ([0040]). As such, Borody teaches formulation for delivery to the intestine.
Regarding claim 126, Borody teaches that the composition can be formulated to resist disintegration in the stomach and permit the inner component to pass intact into the duodenum or to be delayed in release ([0076]). A variety of components can be used for such enteric layers including a number of polymeric acids and mixtures of polymeric acids such as shellac, cetyl alcohol and cellulose acetate (Id.). Accordingly, Borody teaches a pharmaceutical composition comprising a pH-sensitive composition comprising one or more enteric polymers.
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.
Previous rejections under 35 U.S.C. § 103
RE: Rejection of claims 110-112, 123-126, and 131-132 under 35 U.S.C. 103 as being unpatentable over Borody et al. (WO 2017075098), as evidenced by Mysara et al. (FEMS Microbiology Ecology, 2017, Vol. 93, pages 1-12), and in view of Von Maltzahn et al. (US 2016/0158294).
Applicant traverses the rejection of record by arguing the following.
First, applicant argues that the presence of certain species in Borody’s and Von Maltzahn’s extensive lists would not have motivated selection of the recited bacterial strains for use in suppressing K. pneumoniae colonization. Specifically, Declarant asserts that naming K. pneumoniae as another target pathogen appears to be “more aspirational than a suggestion that any given bacterium can and should be used in inhibiting K. pneumoniae replication or survival and it is implausible that any given bacterium listed in Borody or Von Maltzahn, let alone a combination of all listed bacteria, would be effective in inhibiting K. pneumoniae replication or survival (Declaration, par. 17). Declarant argues that “given the presence of at least one species previously known to enhance K. pneumoniae replication or survival, it is simply not plausible that any given bacterium from this list is effective in inhibiting K. pneumoniae replication or survival.
Second, Declarant asserts that given the lengthy list of bacteria provided in Von Maltzahn (or Borody), a person having ordinary skill would not have had any reason to select a bacterium belonging to F. mortiferum or having a 16S rDNA sequence recited in (vii) of claim 110 from Table 1 of Von Maltzahn to inhibit K. pneumoniae replication or survival.
Finally, Declarant asserts that given the length list of bacteria provided in Von Maltzahn (or Borody), a person having ordinary skill in the art could not have predicted that F. mortiferum would be capable of inhibiting K. pneumoniae replication or survival.
Applicant’s arguments and Declarant’s statement have been fully considered but are not sufficient to overcome the rejection of record.
For the reasons discussed above in the 35 U.S.C. § 102 section of this action, Borody anticipates the claimed method. The relevant question for the § 103 analysis as applied to claims 111-112, and 131-132 is whether there exists sufficient motivation to use Von Maltzahn’s F. mortiferum (previously shown to have 99% identity to SEQ ID NO: 75) in Borody’s method of suppressing colonization by a pathogenic bacterium belonging to the species Klebsiella pneumoniae. As discussed in the rejection of record, Von Maltzahn teaches F. mortiferum as a bacterium capable of populating the GI tract for protective or therapeutic effect against infection by one or more GI pathogens of interest including K. pneumoniae. Accordingly, there is considered sufficient motivation to replace Borody’s generic “F. mortiferum” with the specific strain taught in Von Maltzahn. There would have been a reasonable expectation of success because both references teach F. mortiferum as being suitable for suppressing colonization with K. pneumoniae.
And although it is acknowledged that Von Maltzahn recites a lengthy list of appropriate microorganisms for this purpose, the teachings of Von Maltzahn (and, for that matter, Borody) must be taken on their face. Because both references teach/suggest the applicability of F. mortiferum in methods of suppressing colonization of K. pneumoniae, the reasonable conclusion is that the species are indeed capable of such an effect. Applicant has provided no evidence that F. mortiferum was suggested to be incapable of suppressing colonization of K. pneumoniae but instead relies on other species being known to have activities differing from what is described in these reference and relies on an argument that both references include a lengthy list of alternatively useable species for the purpose.
The examiner appreciates the argument supplied by Declarant including the large number of combinations resulting from Von Maltzahn’s disclosure and Von Maltzahn’s focus on C. difficile infection but the pertinent question for determining obviousness in this case is whether it would have been obvious to have arrived at a method of suppressing colonization with the elected species (a composition comprising a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 75). In order to anticipate or render obvious the instant claims, a person having ordinary skill in the art need not use a combination of each of Borody or Von Maltzahn’s species/strains, instead, said person would merely need to recognize that both references teach the usefulness of F. mortiferum for suppressing K. pneumoniae. In this case both references provide sufficient suggestion to arrive at this method with a reasonable expectation of success because, despite the number of other alternative solutions, they nonetheless teach this exact effect.
For at least these reasons, the rejection of record is proper and must be maintained.
RE: Rejection of claims 110, 116-117, 123-126, and 128-130 under 35 U.S.C. 103 as being unpatentable over Borody et al. (WO 2017075098), as evidenced by Mysara et al. (FEMS Microbiology Ecology, 2017, Vol. 93, pages 1-12), and in view of Atarashi et al. (Science, 2017, Vol. 358(6361), pages 359-365; cited in IDS filed on 09/27/2024).
Applicant has not separately argued the merits of this rejection but argues that Atarashi does not remedy the alleged deficiencies of Borody.
For at least the reasons discussed above, the rejection over Borody is proper and this rejection is similarly maintained.
RE: Rejection of claims 110, 116-117, 124-126, 128-130, and 133-138 under 35 U.S.C. 103 as being unpatentable over Borody et al. (WO 2017075098), as evidenced by Mysara et al. (FEMS Microbiology Ecology, 2017, Vol. 93, pages 1-12), and in view of Atarashi et al. (Science, 2017, Vol. 358(6361), pages 359-365; cited in IDS filed on 09/27/2024) and Von Maltzahn et al. (US 2016/0158294).
Applicant has not separately argued the merits of this rejection but argues that Atarashi and Von Maltzahn do not remedy the alleged deficiencies of Borody.
For at least the reasons discussed above, the rejection over Borody is proper and this rejection is similarly maintained.
Maintained rejection under 35 U.S.C. § 103
Claims 110-112, 124-126, and 131-132 are rejected under 35 U.S.C. 103 as being unpatentable over Borody et al. (WO 2017075098), as evidenced by Mysara et al. (FEMS Microbiology Ecology, 2017, Vol. 93, pages 1-12), and in view of Von Maltzahn et al. (US 2016/0158294).
The teachings of Borody and Mysara are set forth above and applied herein. Borody, as evidenced by Mysara, renders obvious claims 110 and 124-126
Regarding claim 111, as discussed above, Borody, as evidenced by Mysara, teaches the method of claim 110.
Borody differs from the instant claim because although Borody’s teaching of administration of a composition comprising F. mortiferum inherently encompasses administration of a bacterium having at least 97% sequence identity, bacteria of the species F. mortiferum may have greater than 97% similarity but less than 99% similarity and there is no teaching or suggestion in Borody which would have led a person having ordinary skill in the art to arrive at administration of a bacterium having at least 99% sequence identity to SEQ ID NO: 75.
Nonetheless, Von Maltzahn et al. (hereinafter Von Maltzahn) teaches methods and compositions for populating the gastrointestinal tract of a subject (abstract). Specifically, Von Maltzahn teaches that in some embodiments, the bacterial composition can provide a protective or therapeutic effect against infection by one or more GI pathogens of interest. Among the possible pathogens taught by Von Maltzahn is K. pneumoniae (p. 66, Table 1; p. 74, Table 3). Von Maltzahn also teaches embodiments wherein the bacterial composition comprises F. mortiferum ([0096]). The exemplary F. mortiferum provided by Von Maltzahn is defined by SEQ ID NO: 897 (p. 66, Table 1). An alignment was performed between the instantly claimed SEQ ID NO: 75 and SEQ ID NO: 897 and demonstrates that the sequences have 99% identity (1013/1023 base pairs; see attached “Sequence Alignment.pdf”).
Therefore, since Borody teaches that a composition comprising F. mortiferum can be administered to a subject in order to suppress colonization by a pathogenic bacterium belonging to the species K. pneumoniae in a subject and because Von Maltzahn also teaches that F. mortiferum can be administered to treat dysbioses such as K. pneumoniae infection in the GI tract, it would have been obvious to have substituted Borody’s generic F. mortiferum with a previously disclosed F. mortiferum such as the one described by Borody (and having “at least 99% sequence identity to the nucleotide sequence of SEQ ID NO: 75”). There would have been a reasonable expectation of success because Von Maltzahn teaches that F. mortiferum is useful for the purpose of treating dysbiosis. There was no teaching or suggestion that the activities of F. mortiferum were strain specific and therefore Von Maltzahn’s F. mortiferum would predictably be capable of exerting the same effect. Additionally, because Borody’s disclosure is limited to a generic F. mortiferum, it would have been obvious to have selected a particular F. mortiferum when practicing the method disclosed by Borody and it would have been obvious to have selected a F. mortiferum strain which was previously disclosed as being useful for treating dysbiosis in the GI tract (i.e., Von Maltzahn’s F. mortiferum). This obviousness is based upon the “Simple Substitution of One Known Element for Another to Obtain Predictable Results” rationale set forth in in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007).
Thus, claim 111 is obvious over Borody, as evidenced by Mysara, and in view of Von Maltzahn.
Regarding claim 112, as discussed above, this claim has been examined in accordance with applicant’s election of “a composition comprising a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 75”.
Accordingly, for the reasons discussed in the rejection of claim 111, Borody, as evidenced by Mysara, and in view of Von Maltzahn makes obvious claim 112.
In the interest of compact prosecution, it is noted that Bacteroides ovatus (corresponding to SEQ ID NO: 45), Bacteroides thetaiotaomicron (corresponding to SEQ ID NO: 46), Clostridium clostridioforme (corresponding to SEQ ID NO: 54), Clostridium innocuum (corresponding to SEQ ID NOs: 55-56), Clostridium sordellii (corresponding to SEQ ID NO: 57), Coprococcus comes (corresponding to SEQ ID NO: 58), Eubacterium rectale (corresponding to SEQ ID NO: 61), Odoribacter splanchnicus (corresponding to SEQ ID NO: 62), Parabacteroides distasonis (corresponding to SEQ ID NO: 63), Blautia obeum (Reclassified from Ruminococcus obeum; corresponding to SEQ ID NO: 66), Collinsella aerofaciens (corresponding to SEQ ID NO: 68), and Bacteroides fragilis (corresponding to SEQ ID NO: 74) are taught by Borody to be includable in a composition for treating K. pneumoniae ([0055], [0057], and [00148]).
Regarding claim 131, this claim limits the composition to comprise the bacterial strain of (vii). (vii) refers to the elected species. Therefore, for the reasons discussed in the rejection of claim 111, the claim is obvious.
Regarding claim 132, this claim limits the composition to further comprise one or more of strains (i)-(vi) and (viii). As discussed above, this claim has been examined in accordance with applicant’s election of “a composition comprising a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 75”. Therefore, for the reasons discussed in the rejection of claim 111, the claim is obvious.
Claims 110, 116-117, 124-126, and 128-130 rejected under 35 U.S.C. 103 as being unpatentable over Borody et al. (WO 2017075098), as evidenced by Mysara et al. (FEMS Microbiology Ecology, 2017, Vol. 93, pages 1-12), and in view of Atarashi et al. (Science, 2017, Vol. 358(6361), pages 359-365; cited in IDS filed on 09/27/2024).
The teachings of Borody and Mysara are set forth above and applied herein. Borody as evidenced by Mysara is found to render obvious claims 110 and 124-126.
Regarding claim 116, as discussed above, Borody teaches the method for suppressing colonization by pathogenic bacterium belonging to the species Klebsiella pneumoniae and teaches the use of one or more microbial species from fecal microbiota for treatment or prophylaxis of various disease states related to the presence of ‘abnormal’ microflora in the GI tract including treatment of inflammatory bowel disease ([0031]).
Borody, however, does not teach that the K. pneumoniae is a pathobiont.
Atarashi et al. (hereinafter Atarashi) teaches that intestinal colonization by bacteria of oral origin has been correlated with several negative health outcomes, including inflammatory bowel disease and Klebsiella spp. tend to colonize when the intestinal microbiota is dysbiotic and elicit a severe gut inflammation (abstract). Specifically, ectopic colonization of the colon by orally derived Klebsiella spp. is associated with aberrant activation of the immune system (p. 6, par. 4). The oral microbiota contains the highest relative abundance of Enterobacteriaceae compared with other mucosal sites and suggests that the oral cavity may serve as a reservoir for Klebsiella pathobionts (Id.). Colonization with multidrug resistant Klebsiella pneumoniae KP-2H7 resulted in a significant increase in colonic TH1 cells (p. 3, par. 3). Atarashi concludes that bacterial species that constitute a small fraction of the oral microbiota can expand and colonize the gut, and a subset of these oral species can induce the accumulation of intestinal TH1 cells (p. 3, par. 1).
As such, because Borody teaches (i) the treatment of Klebsiella pneumoniae by administering a bacterium having at least 97% sequence identity to SEQ ID NO: 75, (ii) the treatment of inflammatory bowel disease, and because (iii) Atarashi teaches that pathobiont K. pneumoniae can travel from the oral cavity into the intestines and increase TH1 response, leading to severe gut inflammation, it would have been obvious for Borody’s method of treating K. pneumoniae to be directed to treatment of a K. pneumoniae pathobiont. There would have been a reasonable expectation of success because Atarashi teaches that the colonization occurs as a result of dysbiosis (p. 6, par. 4) and as such, performing Borody’s method would be expected to suppress colonization of the pathobiont K. pneumoniae by restoring the normal gut flora. This obviousness is based upon the “Some Teachings, Suggestion, or Motivation in the Prior Art That Would Have Led One of Ordinary Skill To Modify the Prior Art Reference or To Combine Prior Art Reference Teachings To Arrive at the Claimed Invention” rationale set forth in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007). See MPEP 2143(I)(G).
Regarding claim 117, as discussed above, Atarashi teaches that intestinal colonization with the pathobiont induces a TH1 response in the intestines. As such, the pathobiont of claim 116 necessarily induces a TH1 response in an intestine of the subject.
Regarding claim 128, Borody teaches a method for treating a disorder selected from a group consisting of carbapenem-resistant Klebsiella pneumoniae.
Borody’s therapeutic composition comprises at least one fecal microorganism selected from a group which comprises F. mortiferum. Although Borody does not teach the 16S rDNA sequence having at least 97% sequence identity to the nucleotide sequence of SEQ ID NO: 75, the teaching of F. mortiferum is sufficient to meet the claim because SEQ ID NO: 75 corresponds to the bacterium F. mortiferum and every species of F. mortiferum would be expected to inherently possess at least 97% sequence identity to the nucleotide sequence of SEQ ID NO: 75. Mysara provides evidence that all species of F. mortiferum inherently possess greater than 97% identity to SEQ ID NO: 75 by teaching that during OTU clustering, groups having sequence similarity are clustered together and the most common cut-off for this is 97% (p. 10, left col., par. 1). This threshold is selected for practical reasons because it offers a compromise between potential inflation due to sequencing errors and a cut-off used for taxonomic classification (Id.). Additionally, Mysara teaches that 97% is commonly used as a threshold for delineating bacterial species and for taxonomic families consisting of species showing high evolutionary conservation, the cut-off will be more stringent than 97% (abstract). Accordingly, the “97%” threshold is a conservative value and therefore Borody’s F. mortiferum would have been reasonably expected to have “at least 97% sequence identity to the nucleotide sequence of SEQ ID NO: 75” as recited in claim 127.
Borody’s methods involve the administration of an effective amount of a therapeutic composition ([0050]) and teaches administering a subject a “pharmaceutically effective dose” of a therapeutic composition comprising live non-pathogenic bacteria ([0032]). Borody’s teachings of “effective amounts” and “pharmaceutically effective doses” are considered to be synonymous with the phrase therapeutically effective amount. This interpretation is supported by applicant’s definition of the phrase which states that “therapeutically effective amount may be used interchangeably with the term ‘effective amount’” (p. 71, lines 22-27).
As such, Borody’s methods differ only in that they do not teach treatment of a disease or disorder associated with Klebsiella pneumoniae colonization.
As discussed above, Atarashi teaches that intestinal colonization by bacteria of oral origin has been correlated with several negative health outcomes, including inflammatory bowel disease and Klebsiella spp. tend to colonize when the intestinal microbiota is dysbiotic and elicit a severe gut inflammation (abstract). Specifically, ectopic colonization of the colon by orally derived Klebsiella spp. is associated with aberrant activation of the immune system (p. 6, par. 4). The oral microbiota contains the highest relative abundance of Enterobacteriaceae compared with other mucosal sites and suggests that the oral cavity may serve as a reservoir for Klebsiella pathobionts (Id.). Colonization with multidrug resistant Klebsiella pneumoniae KP-2H7 resulted in a significant increase in colonic TH1 cells (p. 3, par. 3). Atarashi concludes that bacterial species that constitute a small fraction of the oral microbiota can expand and colonize the gut, and a subset of these oral species can induce the accumulation of intestinal TH1 cells (p. 3, par. 1).
Accordingly, because Borody teaches treatment of K. pneumoniae infection and because Atarashi teaches that K. pneumoniae growth in the gut can significantly increase colonic TH1 cells and contribute to inflammatory bowel disease, it would have been obvious to have modified Borody’s methods such that they are directed to treatment of a disease or disorder associated with Klebsiella pneumoniae rather than treating Klebsiella pneumoniae itself. There would have been a reasonable expectation of success for this modification because Atarashi demonstrates that the TH1 immune response and inflammatory bowel disease follow K. pneumoniae colonization in the gut. Thus, treatment of K. pneumoniae would be expected to lead to treatment of the disease or disorder associated therewith. This obviousness is based upon the “Some Teachings, Suggestion, or Motivation in the Prior Art That Would Have Led One of Ordinary Skill To Modify the Prior Art Reference or To Combine Prior Art Reference Teachings To Arrive at the Claimed Invention” rationale set forth in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007). See MPEP 2143(I)(G).
And although the claim now requires that the method occurs by inhibiting replication or survival of the bacterium belonging to the species Klebsiella pneumoniae, Borody is considered to inherently teach this function by teaching that F. mortiferum can treat K. pneumoniae infection. Alternatively, even if Borody does not teach that the effect is by inhibiting replication or survival, "the discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." (MPEP § 2112(I)). Accordingly, there is no requirement that Borody taught how the method functioned.
Thus, claim 128 is obvious over Borody, as evidenced by Mysara, and in view of Atarashi.
Regarding claim 129, as discussed above, the obvious method is one which treats a disease or disorder associated with a TH1 immune response or an inflammatory bowel disease.
Regarding claim 130, Borody teaches a method for treating a disorder selected from a group consisting of carbapenem-resistant Klebsiella pneumoniae.
Borody’s therapeutic composition comprises at least one fecal microorganism selected from a group which comprises F. mortiferum. Although Borody does not teach the 16S rDNA sequence having at least 97% sequence identity to the nucleotide sequence of SEQ ID NO: 75, the teaching of F. mortiferum is sufficient to meet the claim because SEQ ID NO: 75 corresponds to the bacterium F. mortiferum and every species of F. mortiferum would be expected to inherently possess at least 97% sequence identity to the nucleotide sequence of SEQ ID NO: 75. Mysara provides evidence that all species of F. mortiferum inherently possess greater than 97% identity to SEQ ID NO: 75 by teaching that during OTU clustering, groups having sequence similarity are clustered together and the most common cut-off for this is 97% (p. 10, left col., par. 1). This threshold is selected for practical reasons because it offers a compromise between potential inflation due to sequencing errors and a cut-off used for taxonomic classification (Id.). Additionally, Mysara teaches that 97% is commonly used as a threshold for delineating bacterial species and for taxonomic families consisting of species showing high evolutionary conservation, the cut-off will be more stringent than 97% (abstract). Accordingly, the “97%” threshold is a conservative value and therefore Borody’s F. mortiferum would have been reasonably expected to have “at least 97% sequence identity to the nucleotide sequence of SEQ ID NO: 75” as recited in claim 127.
Borody’s methods involve the administration of an effective amount of a therapeutic composition ([0050]) and teaches administering a subject a “pharmaceutically effective dose” of a therapeutic composition comprising live non-pathogenic bacteria ([0032]). Borody’s teachings of “effective amounts” and “pharmaceutically effective doses” are considered to be synonymous with the phrase therapeutically effective amount. This interpretation is supported by applicant’s definition of the phrase which states that “therapeutically effective amount may be used interchangeably with the term ‘effective amount’” (p. 71, lines 22-27).
As such, Borody’s methods differ only in that they do not explicitly teach that the method is for suppressing colonization and do not teach that the suppression is in an intestine of a subject with an oral microbiome bacterium. Nonetheless, Borody’s method of treating Klebsiella pneumoniae is equivalent to the instantly recited method of “suppressing colonization”. This interpretation is consistent with applicant’s definition for the term “suppressing” which refers to “any form of inhibiting an undesired bacteria” (p. 64, lines 5-7).
Moreover, as discussed above, Atarashi teaches that intestinal colonization by bacteria of oral origin has been correlated with several negative health outcomes, including inflammatory bowel disease and Klebsiella spp. tend to colonize when the intestinal microbiota is dysbiotic and elicit a severe gut inflammation (abstract). Specifically, ectopic colonization of the colon by orally derived Klebsiella spp. is associated with aberrant activation of the immune system (p. 6, par. 4). The oral microbiota contains the highest relative abundance of Enterobacteriaceae compared with other mucosal sites and suggests that the oral cavity may serve as a reservoir for Klebsiella pathobionts (Id.). Colonization with multidrug resistant Klebsiella pneumoniae KP-2H7 resulted in a significant increase in colonic TH1 cells (p. 3, par. 3). Atarashi concludes that bacterial species that constitute a small fraction of the oral microbiota can expand and colonize the gut, and a subset of these oral species can induce the accumulation of intestinal TH1 cells (p. 3, par. 1).
Accordingly, because Borody teaches treatment of K. pneumoniae infection and because Atarashi teaches that oral K. pneumoniae growth in the gut can significantly increase colonic TH1 cells and contribute to inflammatory bowel disease, it would have been obvious to have modified Borody’s methods such that the method is instead directed to suppressing colonization of an intestine of a subject with an oral microbiome bacterium belonging to the species Klebsiella pneumoniae. There would have been a reasonable expectation of success for this modification because Borody teaches the composition as being suitable for treating a generic carbapenem-resistant K. pneumoniae and because Atarashi teaches that oral K. pneumoniae can travel from the oral microbiome and cause infection and inflammation by colonizing the gut. This obviousness is based upon the “Some Teachings, Suggestion, or Motivation in the Prior Art That Would Have Led One of Ordinary Skill To Modify the Prior Art Reference or To Combine Prior Art Reference Teachings To Arrive at the Claimed Invention” rationale set forth in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007). See MPEP 2143(I)(G).
And although the claim now requires that the method occurs by inhibiting replication or survival of the oral microbiome bacterium, Borody is considered to inherently teach this function by teaching that F. mortiferum can treat K. pneumoniae infection. Alternatively, even if Borody does not teach that the effect is by inhibiting replication or survival, "the discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." (MPEP § 2112(I)). Accordingly, there is no requirement that Borody taught how the method functioned.
Thus, claim 130 is obvious over Borody, as evidenced by Mysara and in view of Atarashi
Claims 110, 116-117, 124-126, 128-130, and 133-138 are rejected under 35 U.S.C. 103 as being unpatentable over Borody et al. (WO 2017075098), as evidenced by Mysara et al. (FEMS Microbiology Ecology, 2017, Vol. 93, pages 1-12), and in view of Atarashi et al. (Science, 2017, Vol. 358(6361), pages 359-365; cited in IDS filed on 09/27/2024) and Von Maltzahn et al. (US 2016/0158294).
The teachings of Borody, Mysara, and Atarashi are set forth above and applied herein. Borody, as evidenced by Mysara, and in view of Atarashi renders obvious claims 110, 116-117, 124-126, and 128-130.
Regarding claim 133, as discussed above, Borody, as evidenced by Mysara, and in view of Atarashi makes obvious the method of claim 128.
Borody differs from the instant claim because although Borody’s teaching of administration of a composition comprising F. mortiferum inherently encompasses administration of a bacterium having at least 97% sequence identity, bacteria of the species F. mortiferum may have greater than 97% similarity but less than 99% similarity and there is no teaching or suggestion in Borody which would have led a person having ordinary skill in the art to arrive at administration of a bacterium having 99% sequence identity to SEQ ID NO: 75.
Nonetheless, Von Maltzahn teaches methods and compositions for populating the gastrointestinal tract of a subject (abstract). Specifically, Von Maltzahn teaches that in some embodiments, the bacterial composition can provide a protective or therapeutic effect against infection by one or more GI pathogens of interest. Among the possible pathogens taught by Von Maltzahn is K. pneumoniae (p. 66, Table 1; p. 74, Table 3). Von Maltzahn also teaches embodiments wherein the bacterial composition comprises F. mortiferum ([0096]). The exemplary F. mortiferum provided by Von Maltzahn is defined by SEQ ID NO: 897 (p. 66, Table 1). An alignment was performed between the instantly claimed SEQ ID NO: 75 and SEQ ID NO: 897 and demonstrates that the sequences have 99% identity (1013/1023 base pairs; see attached “Sequence Alignment.pdf”).
Therefore, since Borody in view of Atarashi makes obvious administering a composition comprising F. mortiferum in order to treat a disease or disorder associated with Klebsiella pneumoniae colonization and because Von Maltzahn also teaches that F. mortiferum can be administered to treat dysbioses such as K. pneumoniae infection in the GI tract, it would have been obvious to have substituted Borody’s generic F. mortiferum with a previously disclosed F. mortiferum such as the one described by Borody (and having “at least 99% sequence identity to the nucleotide sequence of SEQ ID NO: 75”). There would have been a reasonable expectation of success because Von Maltzahn teaches that F. mortiferum is useful for the purpose of treating dysbiosis. There was no teaching or suggestion that the activities of F. mortiferum were strain specific and therefore Von Maltzahn’s F. mortiferum would predictably be capable of exerting the same effect. Additionally, because Borody’s disclosure is limited to a generic F. mortiferum, it would have been obvious to have selected a particular F. mortiferum when practicing the method disclosed by Borody and it would have been further obvious to have selected a F. mortiferum strain which was previously disclosed as being useful for treating dysbiosis in the GI tract (i.e., Von Maltzahn’s F. mortiferum). This obviousness is based upon the “Simple Substitution of One Known Element for Another to Obtain Predictable Results” rationale set forth in in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007).
Thus, claim 133 is obvious over Borody, as evidenced by Mysara, and in view of Atarashi and Von Maltzahn.
Regarding claim 134, this claim limits the composition to comprise the bacterial strain of (vii). (vii) refers to the elected species. Therefore, for the reasons discussed in the rejection of claim 133, the claim is obvious.
Regarding claim 135, this claim limits the composition to further comprise one or more of strains (i)-(vi) and (viii). As discussed above, this claim has been examined in accordance with applicant’s election of “a composition comprising a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 75”. Therefore, for the reasons discussed in the rejection of claim 133, the claim is obvious.
Regarding claim 136, as discussed above, Borody, as evidenced by Mysara, and in view of Atarashi makes obvious the method of claim 130.
Borody differs from the instant claim because although Borody’s teaching of administration of a composition comprising F. mortiferum inherently encompasses administration of a bacterium having at least 97% sequence identity, bacteria of the species F. mortiferum may have greater than 97% similarity but less than 99% similarity and there is no teaching or suggestion in Borody which would have led a person having ordinary skill in the art to arrive at administration of a bacterium having 99% sequence identity to SEQ ID NO: 75.
Nonetheless, Von Maltzahn teaches methods and compositions for populating the gastrointestinal tract of a subject (abstract). Specifically, Von Maltzahn teaches that in some embodiments, the bacterial composition can provide a protective or therapeutic effect against infection by one or more GI pathogens of interest. Among the possible pathogens taught by Von Maltzahn is K. pneumoniae (p. 66, Table 1; p. 74, Table 3). Von Maltzahn also teaches embodiments wherein the bacterial composition comprises F. mortiferum ([0096]). The exemplary F. mortiferum provided by Von Maltzahn is defined by SEQ ID NO: 897 (p. 66, Table 1). An alignment was performed between the instantly claimed SEQ ID NO: 75 and SEQ ID NO: 897 and demonstrates that the sequences have 99% identity (1013/1023 base pairs; see attached “Sequence Alignment.pdf”).
Therefore, since Borody in view of Atarashi makes obvious administering a composition comprising F. mortiferum in order to suppress colonization of an intestine of a subject with an oral microbiome bacterium belonging to the species Klebsiella pneumoniae and because Von Maltzahn also teaches that F. mortiferum can be administered to treat dysbioses such as K. pneumoniae infection in the GI tract, it would have been obvious to have substituted Borody’s generic F. mortiferum with a previously disclosed F. mortiferum such as the one described by Borody (and having “at least 99% sequence identity to the nucleotide sequence of SEQ ID NO: 75”). There would have been a reasonable expectation of success because Von Maltzahn teaches that F. mortiferum is useful for the purpose of treating dysbiosis. There was no teaching or suggestion that the activities of F. mortiferum were strain specific and therefore Von Maltzahn’s F. mortiferum would predictably be capable of exerting the same effect. Additionally, because Borody’s disclosure is limited to a generic F. mortiferum, it would have been obvious to have selected a particular F. mortiferum when practicing the method disclosed by Borody and it would have been further obvious to have selected a F. mortiferum strain which was previously disclosed as being useful for treating dysbiosis in the GI tract (i.e., Von Maltzahn’s F. mortiferum). This obviousness is based upon the “Simple Substitution of One Known Element for Another to Obtain Predictable Results” rationale set forth in in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007).
Thus, claim 136 is obvious over Borody, as evidenced by Mysara, and in view of Atarashi and Von Maltzahn.
Regarding claim 137, this claim limits the composition to comprise the bacterial strain of (vii). (vii) refers to the elected species. Therefore, for the reasons discussed in the rejection of claim 136, the claim is obvious.
Regarding claim 138, this claim limits the composition to further comprise one or more of strains (i)-(vi) and (viii). As discussed above, this claim has been examined in accordance with applicant’s election of “a composition comprising a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 75”. Therefore, for the reasons discussed in the rejection of claim 136, the claim is obvious.
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.
Previous double patenting rejections
Applicant has not argued the merits of the provisional rejections of record but argues that because the claims are allegedly in condition for allowance, the provisional double patenting rejection should be withdrawn per the procedures set forth in MPEP § 804(I)(B)(1)(b).
The examiner will make the appropriate determination for withdrawal of the provisional double patenting rejection should the application become in condition for allowance before the copending application issues as a patent. However, for at least the reasons discussed above, the application is not in condition for allowance and the provisional rejections must be maintained.
Maintained double patenting rejections
Claims 110-112, 116-117, 125-126, 128-129, and 131-135 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 176, 182-184, 190-193, 195, and 197-199 of copending Application No. 17/633,930.
Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
Regarding claim 110, the claims of the ‘930 application are directed to methods for suppressing colonization by a pathogenic bacterium belonging to the species Klebsiella pneumoniae in a subject, the method comprising administering to the subject a therapeutically effective amount of a composition comprising inter alia Fusobacterium mortiferum. As discussed above, applicant’s SEQ ID NO: 75 is descriptive of F. mortiferum. Because the instant claims and the copending claims are both open-ended compositions (introduced by the transitional phrase “comprising”), they are open to unrecited components and therefore overlap in scope. And although the copending claim 176 requires the composition to not comprise B. fragilis or P. bifermentans, the instant claim does not require either of these components.
Regarding claim 111, although this claim limits the similarity to 99%, because the copending application teaches the species, it encompasses all of the bacteria having 99% identity to the recited sequence. Accordingly, the claims overlap in scope.
Regarding claim 116, claim 182 of ‘930 teaches the K. pneumoniae being a pathobiont.
Regarding claim 117, claim 184 of ‘930 teaches the TH1 response.
Regarding claim 125, claim 190 of ‘930 teaches the formulation for delivery to an intestine of the subject.
Regarding claim 126, claim 192 of ‘930 teaches that the composition comprises a pH-sensitive composition comprising one or more enteric polymers.
Regarding claim 128, claim 198 of ‘930 teaches the method of suppressing a disease or disorder associated with colonization by a pathobiont belonging to the species Klebsiella pneumoniae comprising administering to the subject a therapeutically effective amount of a composition comprising inter alia Fusobacterium mortiferum. As discussed above, applicant’s SEQ ID NO: 75 is descriptive of F. mortiferum. Because the instant claims and the copending claims are both open-ended compositions (introduced by the transitional phrase “comprising”), they are open to unrecited components and therefore overlap in scope. And although the copending claim 176 requires the composition to not comprise B. fragilis or P. bifermentans, the instant claim does not require either of these components.
Regarding claim 129, claim 198 of ‘930 teaches that the disorder induces a TH1 response and claim 199 of ‘930 teaches the other recited elements.
Regarding claim 131, as discussed above, the claims of ‘930 teach F. mortiferum and this is the bacterial strain of (vii).
Regarding claim 132, the claims of ‘930 teach additional elements including the bacterial species represented by SEQ ID NOs: 48, 50, and 60 (B. vulgatus, B. longum, and E. ramosum, respectively).
Regarding claim 133, although this claim limits the similarity to 99%, because the copending application teaches the species, it encompasses all of the bacteria having 99% identity to the recited sequence. Accordingly, the claims overlap in scope.
Regarding claim 134, as discussed above, the claims of ‘930 teach F. mortiferum and this is the bacterial strain of (vii).
Regarding claim 135, the claims of ‘930 teach additional elements including the bacterial species represented by SEQ ID NOs: 48, 50, and 60 (B. vulgatus, B. longum, and E. ramosum, respectively).
This is a provisional nonstatutory double patenting rejection.
Claims 110-112, 116-117, 124-126, 128-129, and 131-135 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 176, 182-184, 190-193, 195, and 197-199 of copending Application No. 17/633,930 in view of Borody et al. (WO 2017/075098).
The teachings of the ‘930 application are set forth above and applied herein.
Regarding claim 124, for the reasons discussed above, claim 110 is unpatentable over the claims of copending application ‘930. Although the copending application does not teach that the composition further comprises a pharmaceutically acceptable excipient, as claimed, this limitation is nonetheless obvious over ‘930 in view of Borody.
Borody teaches pharmaceutical compositions and methods suitable for the treatment of diseases in mammals [0001]. More specifically, Borody discloses the treatment of various diseases such as gastrointestinal diseases in humans using fecal microbiota-related therapy (Id.). Borody teaches that mammals harbor diverse microbial species in their gastrointestinal (GI) tracts and a healthy microbiota provides the host with benefits including colonization resistance to a broad spectrum of pathogens, nutrient biosynthesis, and immune stimulation that maintains a healthy gut epithelium and systemic immunity ([0002]). Borody teaches that the composition is a “therapeutic composition” and can be provided together with a pharmaceutically acceptable carrier such as an excipient in order to permit the formation of a pharmaceutical composition ([0072]).
As such, because (i) the copending claims are directed to a method for suppressing colonization by a pathogenic bacterium belonging to the species K. pneuminae including a therapeutically effective amount of bacteria such as F. mortiferum, (ii) because the copending claims teach pharmaceutical compositions (claims 190-191), and (iii) because Borody teaches “therapeutic compositions” can be combined with excipients to provide pharmaceutical compositions, it would have been obvious to have included a pharmaceutically acceptable excipient in the pharmaceutical composition.
Claims 110-112, 116-117, 125-126, 128-130, and 131-138 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 176, 182-184, 190-193, 195, and 197-199 of copending Application No. 17/633,930 in view of Atarashi et al. (Science, 2017, Vol. 358(6361), pages 359-365; cited in IDS filed on 09/27/2024).
The teachings of the ‘930 application are set forth above and applied herein.
Regarding claim 130, claim 176 of ‘930 is directed to a method of suppressing colonization by a pathogenic bacterium belonging to the species K. pneumoniae comprising administering to the subject a therapeutically effective amount of a composition comprising inter alia Fusobacterium mortiferum. As discussed above, applicant’s SEQ ID NO: 75 is descriptive of F. mortiferum. Because the instant claims and the copending claims are both open-ended compositions (introduced by the transitional phrase “comprising”), they are open to unrecited components and therefore overlap in scope. And although the copending claim 176 requires the composition to not comprise B. fragilis or P. bifermentans, the instant claim does not require either of these components.
The copending claim differs in that it does not require the K. pneumoniae to be an oral microbiome bacterium.
Atarashi teaches that intestinal colonization by bacteria of oral origin has been correlated with several negative health outcomes, including inflammatory bowel disease and Klebsiella spp. tend to colonize when the intestinal microbiota is dysbiotic and elicit a severe gut inflammation (abstract). Specifically, ectopic colonization of the colon by orally derived Klebsiella spp. is associated with aberrant activation of the immune system (p. 6, par. 4). The oral microbiota contains the highest relative abundance of Enterobacteriaceae compared with other mucosal sites and suggests that the oral cavity may serve as a reservoir for Klebsiella pathobionts (Id.). Colonization with multidrug resistant Klebsiella pneumoniae KP-2H7 resulted in a significant increase in colonic TH1 cells (p. 3, par. 3). Atarashi concludes that bacterial species that constitute a small fraction of the oral microbiota can expand and colonize the gut, and a subset of these oral species can induce the accumulation of intestinal TH1 cells (p. 3, par. 1).
Thus, because the claims of ‘930 are directed to treating a generic K. pneumoniae and because Atarashi teaches that oral K. pneumoniae can enter the digestive tract and cause infection and inflammation, it would have been obvious to have modified the method of ‘930 such that the K. pneumoniae suppressed in the method is an oral K. pneumoniae.
Regarding claim 136, although this claim limits the similarity to 99%, because the copending application teaches the species, it encompasses all of the bacteria having 99% identity to the recited sequence. Accordingly, the claims overlap in scope.
Regarding claim 137, as discussed above, the claims of ‘930 teach F. mortiferum and this is the bacterial strain of (vii).
Regarding claim 138, the claims of ‘930 teach additional elements including the bacterial species represented by SEQ ID NOs: 48, 50, and 60 (B. vulgatus, B. longum, and E. ramosum, respectively).
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowed.
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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/GRANT C CURRENS/Examiner, Art Unit 1651
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