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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 01/21/2026 has been entered.
Status of Claims
Claims 17-18, 20-24 and 26-46 are pending following the Reply filed 01/21/2026. Claims 17, 23, 28, 36 and 40 have been amended without introducing new matter. Claims 28-44 are withdrawn. Accordingly, claims 17-18, 20-24, 26-27 and 45-46 are presently considered.
Withdrawn
The rejections of claims 17-18, 20-24, 26-27 and 45-46 under 35 U.S.C. 101 as being directed to a judicial exception (product of nature) is withdrawn in light of the amendments. Specifically, the independent claims now recite the composition comprising one or more stabilisers and/or cryoprotectants, which results in longer shelf life of the bacterial composition and enables the composition to be freeze dried for storage. See Response to Arguments below for further discussion.
Claim Objections
Claim 26 is objected to because of the following informalities: the claim recites “2, 3, 4, 5, 6, 7, 8, 9, 1, 11, 12, 13 or 14 different bacterial species” in line 2 (emphasis added). In view of the instant claims, (i.e., parent claim 23), it appears Applicant intended the “1” to be a “10”, which further limits the subject matter of the claim (i.e., to require at least 2 bacterial species). Please amend “9, 1, 11” in line 2 to recite “9, 10, 11”. Appropriate correction is required.
In the interest of compact prosecution, the claim is interpreted in accordance with the correction above, i.e., as requiring “2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 different bacterial species”.
Maintained rejections and new rejections necessitated by amendment
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 17-18, 20-24, 26-27 and 45-46 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 17 recites the phrase “a sample” in lines 3-4 and again in line 7, which renders the claim indefinite, because the limitation has unclear antecedent basis. Specifically, it is unclear if the limitation refers to the “faecal sample” introduced in line 1 or to another sample. In view of the specification, a “relative abundance” as applied to a bacterium in a sample refers to the abundance of the bacterium in the sample “as a proportion of the total microbiota in the sample or a reference sample” (see pg. 50, lines 30-33, emphasis added). Hence, it is not clear whether “a sample” refers to the faecal sample of the claim or to some other (reference) sample.
In the interest of compact prosecution, “a sample” is broadly interpreted to be any faecal sample. As such, the composition having a “relative abundance” of the bacteria may contain a plurality of the bacteria in any amount.
Suggestion to obviate the rejection: Applicant may amend the phrase “a sample” recited in lines 3-4 and 7 to recite “the sample”.
Claim 23 recites the phrase “a sample” in line 7, which renders the claim indefinite, because the limitation has unclear antecedent basis. Specifically, it is unclear if the limitation refers to the “faecal sample” introduced in line 1 or to another sample. In view of the specification, a “relative abundance” as applied to a bacterium in a sample refers to the abundance of the bacterium in the sample “as a proportion of the total microbiota in the sample or a reference sample” (see pg. 50, lines 30-33, emphasis added). Hence, it is not clear whether “a sample” refers to the faecal sample of the claim or to some other (reference) sample.
In the interest of compact prosecution, “a sample” is broadly interpreted to be any faecal sample, including a reference sample comprising any amount of the bacteria. As such, the composition having a “relative abundance” of the bacteria may contain a plurality of the bacteria in any amount.
Suggestion to obviate the rejection: Applicant may amend the phrase “a sample” recited in line 7 to recite “the sample”.
Claim Rejections - 35 USC § 102
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.
Claim(s) 17-18, 21-24 and 27 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Schneider, et al. (U.S. Patent 9,999,641 B2; cited on Form 892), hereafter, “Schneider”.
Regarding claim 17, Schneider teaches a composition comprising two or more purified bacterial strains, wherein the two or more purified bacterial strains comprise 16S rDNA sequences having at least 97% homology with nucleic acid sequences selected from the group that includes SEQ ID NO: 19 (see col. 7, lines 16-23). Schneider teaches that the bacterial strains are isolated from the fecal matter of healthy individuals (see col. 67, lines 44-49). Schneider teaches the composition further comprises stabilizers (see col. 72, lines 35-38). As shown in the following alignment, Schneider’s SEQ ID NO: 19 (bottom) shares more than 99% identity with instant SEQ ID NO 8 (top):
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Regarding the limitation, “wherein the presence or relative abundance of one or more bacteria as a proportion of the total microbiota in a sample is associated with a response to cancer with a checkpoint inhibitor therapy”, this limitation refers to an inherent property of the bacteria themselves and is satisfied by the presence of the recited bacteria in the composition without requiring any further structure to said composition. Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). In the instant case, Schneider teaches the composition comprising the same bacteria as the claim, which are inherently associated with a response to checkpoint inhibitor therapy.
Thus, Schneider teaches a composition comprising a faecal sample and one or more stabilizers, wherein the composition has a presence of bacteria having at least 98.7% sequence identity with instant SEQ ID NO: 8, which meets the claim.
Regarding claim 18, Schneider teaches the bacterial strains are lyophilized (see col. 12, lines 59-60) and the composition may be in the form of a lyophilized formulation (see col. 72, lines 35-27).
Regarding claim 21, Schneider teaches the composition can be in the form of a capsule, tablet or liquid (see col. 72, lines 42-44).
Regarding claim 22, Schneider does not explicitly teach the bacteria are associated with a response to cancer with a checkpoint inhibitor therapy, wherein the checkpoint inhibitor therapy inhibits PD-1, PDL-1, PDL-2, TIM-3, TIGIT, LAG-3 or CTLA-4 activity. However, as discussed regarding claim 17, this limitation refers to an inherent property of the bacteria themselves and is satisfied by the presence of the recited bacteria in the composition.
Regarding claim 23, Schneider teaches a composition comprising a faecal sample and one or more stabilizers, wherein the composition has the presence of a bacterium having at least 98.7% sequence identity with instant SEQ ID NO: 8, as discussed regarding claim 17. Regarding the limitation, “wherein said faecal sample has been supplemented”, this limitation is a product-by-process step which does not change the structure of the claimed product when compared to the composition of claim 17. Regarding the limitation of a “relative abundance… as a proportion of the total microbiota in a sample”, Schneider teaches the composition may contain, for example, 105 CFUs or more of each bacteria, with some strains more abundant than others, wherein the total bacteria in the composition may be 1010 CFUs or more (see col. 75, lines 18-31, 39-44). Hence, Schneider discloses every element required by claim 23.
Regarding claim 24, Schneider teaches the bacterial strains are lyophilized (see col. 12, lines 59-60) and the composition may be in the form of a lyophilized formulation (see col. 72, lines 35-27).
Regarding claim 27, Schneider teaches the composition can be in the form of a capsule, tablet or liquid (see col. 72, lines 42-44).
Claim(s) 17, 20 , 23 and 26 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Ford, et al. (U.S. Patent 12,214,002 B2; effectively filed 10/30/2017; cited on Form 892), hereafter, “Ford”, as evidenced by Santiago (previously cited).
Regarding claim 20, Ford teaches a composition prepared from bacteria that are isolated from stool (see col. 6, lines 55-57), the composition comprising 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14 species listed in Table 3 (see col. 2, lines 27-29), which includes SEQ ID NO: 247 (see Table 3, col. 22, “Clostridum_sp_KLE_1755”) and SEQ ID NO: 208 (see Table 3, col. 23, “Eubacterium_sp_3_1_31”).
As shown in the following alignment, Ford’s SEQ ID NO: 247 (bottom) shares more than 98.7% sequence identity with instant SEQ ID NO: 1 (top):
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As shown in the following alignment, Ford’s SEQ ID NO: 208 (bottom) shares more than 98.7% sequence identity with instant SEQ ID NO: 7 (top):
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Regarding the limitation of “one or more stabilisers and/or cryoprotectants”, Ford teaches the composition further comprises one or more pharmaceutical excipients which may include sucrose, gelatin, glycerol, and/or polyethylene glycol (see col. 12, lines 16-18, 35-40). In view of Santiago, sucrose, gelatin, glycerol, and polyethylene glycol are all cryoprotectants, which are substances added to a formulation in order to protect an active ingredient during freezing (see pg. 52, para. [0202]). Hence, the excipients taught by Ford meet the claimed limitation of “one or more cryoprotectants”, as evidenced by Ford. See MPEP 2131.01 which states extra references can be used to show the meaning of a term used in the primary reference.
Hence, Ford discloses every element required by claim 20.
Regarding claim 26, the limitation, “wherein said faecal sample has been supplemented”, recited in claim 23 (from which claim 26 depends), is a product-by-process step which does not change the structure of the claimed product. Hence, Ford discloses every element required by claim 26, as presented above regarding claim 20.
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.
Claim(s) 45-46 is/are rejected under 35 U.S.C. 103 as being unpatentable over Schneider as applied to claims 17-18, 21-24 and 27 above, and further in view of Santiago.
Regarding claim 45, Schneider teaches a composition comprising a faecal sample and one or more stabilizers, wherein the composition has a presence of bacteria having at least 98.7% sequence identity with instant SEQ ID NO: 8, as discussed regarding claim 17. Schneider also teaches a method for treating pathogenic infections, such as Clostridium difficile infections, by administering the composition to a subject in need (see col. 1, lines 15-18). Schneider teaches that Clostridium difficile infections (CDI) are the direct result of dysbiosis from antibiotic use and cause diarrhea which may ultimately lead to death (see col. 1, lines 38-42). Schneider teaches that the Center for Disease Control currently classifies CDI as a public health threat requiring immediate and aggressive action because of its natural resistance to many drugs and the emergence of a fluoroquinolone-resistant strain that is now prevalent throughout North America and Europe (see col. 1, lines 49-56).
Schneider does not teach the composition comprising bacteria that comprise a sequence having at least 98.7% sequence identity with a nucleic acid sequence of SEQ ID NO: 5.
Santiago teaches compositions and methods for delivery of novel mixtures of bacterial strains for the decolonization and/or eradication of various pathogenic bacteria, particularly, antibiotic-resistant bacteria (see Abstract), including Clostridium difficile (see pg. 2, para. [0023]). Santiago teaches that Antibiotic-Resistant Bacteria (ARB) are a major health care challenge in the US and around the world (see pg. 1, para. [0004]) and there are currently no therapies for decolonizing and/or eradicating ARB from GI-colonized patients (see pg. 1, para. [0007]).
Santiago teaches a pharmaceutical composition comprising a bacterial mixture which includes at least one bacterial strain comprising a 16S rRNA sequence of any one of the operational taxonomic units (OTUs) recited in Table 5 or 6 (see pg. 1, para. [0009]) which includes Alistipes indistinctus, represented by the DNA sequence, SEQ ID NO. 1033 (see pg. 38, Table 5, col. 2). In Santiago’s Examples, each strain of the bacterial mixture may be cultivated to a concentration of about 1010 CFU/mL in formulating the pharmaceutical composition (see pg. 67, para. [0333]). As shown in the following alignment, the full length of instant SEQ ID NO. 5 (top) shares 100% sequence identity with SEQ ID NO. 1033 of Santiago (bottom):
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It would have been obvious at the time of filing for a person of ordinary skill in the art to have arrived at the claimed invention by combining the teachings of Schneider and Santiago, because both references teach bacterial compositions that can be used to treat Clostridium difficile infections. One would have been particularly motivated to do so, because both references teach antibiotic-resistant pathogenic bacteria, including C. difficile, are a global problem and can be decolonized in the gut by the introduction of beneficial bacteria. One would have recognized that any of the bacterial species/strains taught by Schneider and Santiago could be used in combination, and that in combination each bacterium merely performs the same function as it does separately. As Santiago teaches strains for use in the composition that are disclosed to have the same effects taught by Schneider, it would have been obvious to have included any of these strains. Hence, the combination would have been readily apparent and deemed to be a mere (A) combining of prior art elements according to known methods to yield predictable results (see MPEP 2143(I): Rationales to support rejections under 35 U.S.C. 103). Furthermore, it is well within the ordinary skill in the art to formulate a faecal bacterial composition by supplementing additional strains known to have beneficial properties.
Regarding claim 46, Schneider teaches every element of claim 23, as discussed above. Hence, claim 46 is obvious for the same reasons as claim 45.
Response to Arguments
Regarding the rejection under 35 U.S.C. 112(b), Applicant argues claims 17 and 23
have been amended herein to read "wherein said faecal sample has a presence or relative abundance of one or more bacteria as a proportion of the total microbiota in a sample." In light of this amendment, a person of skill in the art would readily understand that the claimed composition requires a presence or relative abundance of one or more of the selected bacteria, and that this relates to the relative abundance being a proportion of the total microbiota in a sample. Applicant cites the specification at pages 50 (lines 30-37) and 51 (lines 1-8).
Applicant’s arguments have been considered but are moot because the new ground of rejection does not pertain to any matter specifically challenged in the argument. As discussed in the present rejection, the claims recite “a faecal sample” and also “a sample”, which raises indefiniteness due to unclear antecedent basis. In this case, it is not clear if the “relative abundance… as a proportion of the total microbiota in a sample” refers to the total microbiota in the “faecal sample” or in another sample. In view of the portion of the specification cited by Applicant, “a sample” may be referring to the faecal sample or to a reference sample. See the present rejection under 35 U.S.C. 112(b) for further discussion.
Regarding the rejections under 35 U.S.C. 101, Applicant argues that claims 17 and 23 have been amended to recite that the pharmaceutical composition further comprises "one or more stabilisers and/or cryoprotectants." The presence of a stabiliser and/or a cryoprotectant within the claimed composition results in greater stability and longer shelf life such that the composition can be used for treatment of a patient for a much longer period of time, and enables the composition to be freeze dried for storage. This is entirely in keeping with the finding of the USPTO's Pomelo Juice example, where a claim reciting a composition comprising naturally-occurring juice and an added preservative (which may or may not be naturally-occurring) is said to be patent-eligible because the composition as a whole has markedly different characteristics from the naturally occurring counterparts, because the juice would spoil more slowly. See USPTO, "Nature-Based Product Claims.," Example 2, claim 2, (December 2014).
Applicant’s arguments have been fully considered and are persuasive. Accordingly, the rejection of the claims under 35 U.S.C. 101 has been withdrawn.
Regarding the rejections under 35 U.S.C. 103 in view of Culler and further in reference of GenBank LT9002171 and GenBank AP019735. l, Applicant argues that Culler, at most, describes Gordonibacter urolithinfaciens DSM 27213T as an exemplary strain in Table 1, and Alistipes sp. 5CBH24 as an exemplary strain in Table 5 and Table 12. These are exhaustive, overinclusive lists of bacteria, and Culler presents no data linking these two particular strains to any response in treating cancer, and certainly does not teach
that the bacterial species with a l6S rDNA sequence according to SEQ ID NOs: 4 or 6 can improve the responsiveness to checkpoint inhibitor therapy. Therefore, Applicant submits that Culler does not provide any pointer to the skilled person to arrive at the present invention.
Applicant’s arguments have been considered but are moot because the new ground of rejection, which was necessitated by Applicant’s amendments to the claims, does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Regarding the rejections of claims 45 and 46 under 35 U.S.C. 103 as being unpatentable over Culler, Genbank LT9002171, Genbank AP019735.1, and further in view of Santiago, Applicant traverses the rejection by arguing that for at least the reason that claim 45 depends from claim 17, and claim 46 depends from claim 23, this rejection is overcome in light of the arguments discussed above.
Applicant’s arguments have been fully considered but they are not persuasive. First, Applicant's arguments fail to comply with 37 CFR 1.111(b) because they amount to a general allegation that the claims define a patentable invention without specifically pointing out how the language of the claims patentably distinguishes them from the references. Further, Applicant's arguments do not comply with 37 CFR 1.111(c) because they do not show how the amendments avoid such references or objections. In the instant case, Applicant has not provided any arguments to address or specifically point out any alleged deficiency regarding the Santiago reference as used in the rejection.
Conclusion
No claims are allowed.
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/DENNIS IGNATIUS ARMATO JR/Examiner, Art Unit 1651
/MELENIE L GORDON/Supervisory Patent Examiner, Art Unit 1651