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 .
Claim status
Following the preliminary amendment filed 12/30/2024, claims 66-85 are pending in the application. Claims 66-85 are presently considered.
Priority
The present application claims status as a 371 (National Stage) of PCT/US2022/023427 filed on 04/05/2022. Applicant’s claim for benefit under 35 U.S.C. 119(e) of Provisional application No. 63/170,903 filed on 04/05/2021 is acknowledged. The present application and all claims are being examined with the earliest effective filing date of 04/05/2021.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 12/30/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 66-79 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature and natural phenomenon without significantly more.
The instant claims recite laws of nature and natural phenomena. These judicial exceptions (JEs) are not integrated into a practical application and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception as explained below:
Subject Matter Eligibility Guidance
A three-step inquiry has been established to determine subject matter eligibility under 35 U.S.C. 101, in accordance with MPEP § 2106:
Step 1. Is the claim directed to a process, machine, manufacture, or composition of matter?
Step 2A. Is the claim directed to a law of nature, natural phenomenon (product of nature), or an abstract idea?
Prong 1 – Does the claim recite a law of nature, natural phenomenon, or an abstract idea?
Product of Nature Definition
When a law of nature or natural phenomenon is claimed as a physical product, the courts have often referred to the exception as a "product of nature". See Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 580, 106 USPQ2d 1972, 1975 (2013); University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 758-59, 113 USPQ2d 1241, 1243 (Fed. Cir. 2014). As explained in those decisions, products of nature are considered to be an exception because they tie up the use of naturally occurring things, but they have been labeled as both laws of nature and natural phenomena. See Myriad Genetics, Inc., 569 U.S. at 590-91, 106 USPQ2d at 1979.
The Markedly Different Characteristics Analysis
The first step in the analysis is to select the appropriate counterpart to the nature-based product. When the nature-based product is derived from a naturally occurring thing, then the naturally occurring thing is the counterpart. See MPEP § 2106.04(c)(II)(A).
The second step in the analysis is to identify appropriate characteristics to compare. Appropriate characteristics must be possessed by the claimed product, because it is the claim that must define the invention to be patented. Cf. Roslin, 750 F.3d at 1338, 110 USPQ2d at 1673. See MPEP § 2106.04(c)(II)(B).
The final step in the markedly different characteristics analysis is to compare the characteristics of the claimed nature-based product to its naturally occurring counterpart in its natural state, in order to determine whether the characteristics of the claimed product are markedly different. See MPEP § 2106.04(c)(II)(C).
Prong 2 – If the claim recites a judicial exception, does it recite additional elements that integrate the judicial exception into a practical application?
Limitations that are indicative of integration into a practical application include:
Improvements to the functioning of a computer, or to any other technology or technical field. See MPEP § 2106.05(a);
Applying the judicial exception with, or by use of, a particular machine. See MPEP § 2106.05(b);
Effecting a transformation or reduction of a particular article to a different state or thing. See MPEP § 2106.05(c);
Applying or using a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition. See MPEP § 2106.05(d);
Applying or using the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception. See MPEP § 2106.05(e).
Step 2B. If the recited judicial exception is not integrated into a practical application, does the claim recite additional elements that amount to significantly different than the judicial exception such that they provide an inventive concept? This step includes evaluation of the same considerations under Step 2A, Prong 2, as well as two additional considerations:
Adding a specific limitation or combination of limitations that are not well-understood, routine, conventional activity in the field, which is indicative that an inventive concept may be present; and
Simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, which is indicative that an inventive concept may not be present.
Analysis
Step 1 (direction to a process, machine, manufacture, or composition of matter):
Claims 66-79 are directed to a composition of matter, which is a statutory category.
Therefore the answer to Step 1 for claims 66-79 is yes.
Step 2A:
Prong One (recitation of a law of nature, natural phenomenon, or an abstract idea):
Claims 66-71 and 79 are directed to a composition comprising a mixture of bacterial strains comprising Collinsella aerofaciens, Bifidobacterium adolescentis, and Faecalibacterium prausnitzii. Claims 68-69 and 71 recite the bacterial mixture further comprising additional strains (e.g., the species Bifidobacterium longum, the genus Dorea, and the species Bacteroides uniformis). Claims 72-78 are directed to a composition comprising a mixture of bacterial strains comprising a 16S rDNA sequence with at least 97% sequence identity to the nucleotide sequences of SEQ ID NOs 1-3, which are disclosed in the specification to be the 16S rDNA sequences of Collinsella aerofaciens, Bifidobacterium adolescentis, and Faecalibacterium prausnitzii, respectively (see pg. 49). Claims 75-76 and 78 recite the bacterial mixture further comprising additional strains (e.g., SEQ ID NOs 4 and 7-20, the genus Dorea), which, in view of the specification, also include, for example, Bifidobacterium longum and Bacteroides uniformis (see pg. 51, “Strain 8” and pg. 56, “Strain 20”).
The specification teaches that these strains are generally isolated from the microbiome of healthy individuals (see pg. 20, lines 32-33), thus the claims recite natural products. In view of the prior art of record, the strains above are commonly present in the human gastrointestinal tract and are cultured from human feces (see, e.g., Rajilic-Stojanovic et al. at FIGs. 3, 6 and 13-14; cited in the IDS filed 12/30/2024) and have been identified as biomarkers of responsiveness to immunotherapy (e.g., anti-PD1/PD-L1 therapy) and to have related therapeutic effects (see Gajewski et al., WO 2018226690 A1, at pg. 2; cited on Form 892), which are appropriate characteristics for comparing the claimed strains to their natural counterparts. In the instant case, there is no evidence within the specification that the claimed bacterial strains are markedly different from their naturally occurring counterparts.
Therefore the answer to Step 2A, Prong One for claims 66-79 is yes because each claim recites products of nature (laws of nature and natural phenomena).
Prong Two (recitation of additional elements that integrate the JE into a practical application):
Claims 72-73, 75 and 77-78 recite “…16S rDNA sequences having at least 97% sequence identity to the nucleotide sequence…” This limitation is merely a representation of the genetic code contained within the organisms and does not effect a transformation or reduction of the microorganisms to a different state or thing.
Claim 74 recites “…16S rDNA sequence with at least 99% sequence identity to the nucleotide sequence…” This limitation is merely a representation of the genetic code contained within the organisms and does not effect a transformation or reduction of the microorganisms to a different state or thing.
Claim 79 recites “wherein the bacterial strains are lyophilized or spray-dried”. This limitation does not necessarily effect a transformation or reduction of the microorganisms to a different state or thing. Chávarri et al. (cited on Form 892) teach that spray drying is a process in which a liquid mixture is atomized and subjected to hot air or other gases to obtain a very rapid drying (pg. 505, para. 1) and that the technique is “not so useful” for the industrial production of encapsulated probiotics because of low survival rate during drying of the bacteria and low stability upon storage (pg. 504, para. 5). Applicant’s specification merely states that spray drying or lyophilization are envisaged embodiments of the invention (pg. 33, lines 14-28) but does not provide any evidence that spray drying or lyophilizing the claimed bacteria causes them to be transformed or reduced into a different state or thing.
Therefore the answer to Step 2A, Prong Two for claims 66-79 is no.
Step 2B (recitation of additional elements that amount to significantly different than the JE such that they provide an inventive concept):
Claims 66-78 do not recite limitations which amount to significantly different than the JE such that they provide an inventive concept.
Claim 79 recites “wherein the bacterial strains are lyophilized or spray-dried”. Chávarri et al. teaches microencapsulation by spray-drying is a “well-established process” and provides a list of probiotic bacteria prepared by spray-drying (see pg. 507, Table 1 and para. 2). Chávarri et al. further teaches that freeze-drying is useful to dry probiotics previously encapsulated by other techniques and it is most often used to dry probiotics (p. 510, par. 4). Thus, this these limitations are considered to be well-understood, routine, conventional activity previously known to the industry.
Therefore, the answer to step (2B) is no.
In conclusion, claims 66-79 are directed to a judicial exception and do not qualify as eligible subject matter under 35 U.S.C. § 101.
Claim Rejections - 35 USC § 112(a) – Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 72-73 and 75-78 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Applicant’s claims are directed to a composition comprising a bacterial mixture of two or more bacterial strains comprising 16S rDNA sequences with at least 97% sequence identity to the nucleotide sequences of SEQ ID NOs 1-3 (claims 72-73 and 75-78) and the bacterial mixture further comprising bacterial strains comprising 16S rDNA sequences with at least 97% sequence identity to the nucleotide sequences of SEQ ID NOs 4 and 7-20 (claims 75-78). Claim 77 is directed to the composition of claim 72, wherein the bacterial mixture does not comprise a bacterial strain comprising a 16S rDNA sequence having 97% sequence identity to SEQ ID NO: 5 and/or SEQ ID NO: 6.
The specification teaches that these sequences (SEQ ID NOs 1-20) correspond with the 16S rDNA sequences of Collinsella aerofaciens, Bifidobacterium adolescentis, Faecalibacterium prausnitzii, Ruminococcus gnavus, Bacteroides fragilis, Anaerostipes caccae, Bacteroides thetaiotaomicron, Bifidobacterium longum, Akkermansia muciniphila, Fusobacterium ulcerans, Eubacterium limosum, Subdoligranulum sp., Phascolarctobacterium faecium, Parabacteroides johnsonii, Paraprevotella xylaniphila, Parabacteroides distasonis, Alistipes sp., Bacteroides dorei, Parabacteroides gordonii, and Bacteroides uniformis, respectively (see pgs. 49-56).
The courts have described the essential question to be addressed in a description requirement issue in a variety of ways. An 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." In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989). Under Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991).
The length of the claimed sequences range from 787 base pairs (SEQ ID NO: 4) to 1557 (SEQ ID NO: 13) base pairs. Therefore, the claimed threshold of at least 97% sequence identity allows for variation of 23-46 base pairs (depending on 16S rDNA sequence length). There is no disclosure in the prior art of the claimed combination of bacteria, wherein each bacterium comprises between 97-98% sequence identity to the aforementioned SEQ ID NOs. Therefore, a person having ordinary skill in the art would be required to rely solely on applicant’s disclosure for support for the claimed invention. Applicant’s Examples recite the taxonomic names of the bacterial strains (e.g., “Collinsella aerofaciens”), but the inventors do not disclose whether these strains comprised the same 16S rDNA sequences represented by SEQ ID NOs 1-20 or to what extent they differed to the claimed sequences. Thus, the breadth of the claims may encompass strains or species not disclosed by applicant, and there is no evidence that applicant was in possession of all the compositions encompassed by the scope of the claims.
For example, the bacteria covered by the scope of >97% sequence identity to SEQ ID NO: 7 includes bacteria having as many as 27 base pairs of variation from the reference sequence (907 x 0.03). Applicant has disclosed Bacteroides thetaiotaomicron as the species corresponding to this sequence (see pg. 50, “Strain 7”). At the time of filing, the breadth of this claim encompassed bacteria which are classified in the art as different species. For example, Caballero, S. (WO 2019118515 A2; cited in the IDS filed 12/30/2024) discloses a strain of Bacteroides faecis represented by SEQ ID NO: 44 (see pg. 125, Table 12) comprising a sequence that shares greater than 97% sequence identity to instant SEQ ID NO: 7 (B. thetaiotaomicron). See “Sequence Alignment, SEQ ID NO: 7 (18/285,548) vs. SEQ ID NO: 44 (WO 2019118515 A2)” cited on Form 892.
Although the 97% identity threshold has been classically used in the art to delineate microorganisms at the species level, applicant has not met the written description requirement because this threshold is not unequivocally capable of species delineation. See Edgar, R. (cited on Form 892) which revisits the 97% threshold which was proposed in 1994 (see Abstract). Specifically, Edgar analyzes the canonical threshold of 97% identity in 16S ribosomal RNA gene sequences. Edgar teaches that it is “well-known that some pairs of species have 16S rRNA sequences with >97% identity and using a fixed threshold cannot reliably identify species” (p. 2372, right col., par. 3). Edgar tests for and identifies many “optimal thresholds” to establish species delineation (summarized on pg. 2373, Table 1). Each threshold is higher than 97% (see pg. 2373, col. 1, par. 1). Edgar concludes “the canonical 97% threshold is far from optimal for all clustering algorithms and should be increased to at least 99%” (pg. 2374, col. 2, par. 3; Abstract).
Therefore, in view of the different species encompassed by such a broad claim, a person having ordinary skill would clearly recognize that applicant was in possession of compositions wherein the bacteria have at least 99% identity to the disclosed sequences but would not clearly recognize that the inventor was in possession of the invention as claimed. Granting of a patent on the claims as currently written would improperly allow the inventor to exclude others from compositions comprising bacteria which were not described by the inventors or adequately demonstrated to be in the possession of the inventors. See MPEP § 2163.
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) 66-77 and 79-81 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Caballero, S. (WO 2019118515 A2; cited in the IDS filed 12/30/2024), hereafter “Caballero”.
Regarding claim 66, Caballero teaches a composition comprising two or more purified bacterial strains selected from a group that includes Collinsella aerofaciens, Bacteroides adolescentis, and Faecalibacterium prausnitzii (see claim 1).
Regarding claim 67, Caballero teaches a composition comprising two or more purified bacterial strains selected from a group that includes Collinsella aerofaciens, Bacteroides adolescentis, and Faecalibacterium prausnitzii (see claim 1). Hence, Caballero teaches embodiments comprising all three of the claimed species.
Regarding claim 68, Caballero teaches the composition further comprising Bifidobacterium longum (see claim 1).
Regarding claim 69, Caballero teaches the composition further comprising Dorea longicatena (see claim 1) which is a member of the genus Dorea.
Regarding claim 70, Caballero teaches the composition comprises two or more purified bacterial strains selected from a group that does not include either Bacteroides fragilis or Anaerostipes caccae (see claim 1). Hence, Caballero teaches embodiments that do not comprise a bacterial strain belonging to either of the claimed species.
Regarding claim 71, Caballero teaches the composition further comprising Bacteroides uniformis (see claim 1).
Regarding claim 72, Caballero teaches the composition comprising Collinsella aerofaciens, Bacteroides adolescentis, and Faecalibacterium prausnitzii, as discussed above. Caballero discloses these species as comprising 16S rDNA sequences represented by SEQ ID NO: 13, SEQ ID NO: 6, and SEQ ID NO: 17, respectively (see pg. 84, lines 29-30; pg. 87, line 34; pg. 85, line 17; pg. 89, line 5).
(i) As shown in the following alignment, Caballero’s SEQ ID NO: 13 (bottom) comprises a sequence that is more than 99% identical to the full length of instant SEQ ID NO: 1 (top):
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Hence, as there is only 1 base pair difference between the sequences, they share more than 99% sequence identity (830/831 base pairs).
(ii) As shown in the following alignment, Caballero’s SEQ ID NO: 6 (bottom) comprises a sequence that is more than 99% identical to the full length of instant SEQ ID NO: 2 (top):
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Hence, as there are only 4 base pair differences between the sequences, they share more than 99% sequence identity (916/920).
(iii) As shown in the following alignment, Caballero’s SEQ ID NO: 17 (bottom) comprises a sequence that is more than 99% identical to instant SEQ ID NO: 3 (top):
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The examiner notes that the last two base pairs of instant SEQ ID NO: 3 are not included in the alignment (the total length is 935 base pairs). Hence, there are a total of 6 base pair differences between the sequences, rendering the sequences more than 99% identical (929/935).
Thus, Caballero teaches the bacterial strains of the composition to comprise sequences that have more than 99% sequence identity with instant SEQ ID NOs 1-3.
Regarding claim 73, Caballero teaches the composition comprising Collinsella aerofaciens, Bacteroides adolescentis, and Faecalibacterium prausnitzii which are disclosed as comprising sequences with more than 99% sequence identity to SEQ ID NOs 1-3, as discussed above.
Regarding claim 74, Caballero teaches the composition comprising Collinsella aerofaciens, Bacteroides adolescentis, and Faecalibacterium prausnitzii which are disclosed as comprising sequences with more than 99% sequence identity to SEQ ID NOs 1-3, as discussed above.
Regarding claim 75, Caballero teaches the composition further comprising Bifidobacterium longum, as discussed above (regarding claim 68). Caballero discloses this species as comprising a 16S rDNA sequence represented by SEQ ID NO: 50 (see pg. 101, line 6). As shown in the following alignment, Caballero’s SEQ ID NO: 50 (bottom) comprises a sequence that is more than 98% identical to instant SEQ ID NO: 8 (top):
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The examiner notes that the first base pair of instant SEQ ID NO: 8 is not included in the alignment (the total length is 931 base pairs). Hence, there are a total of 10 base pair differences between the sequences, rendering the sequences more than 98% identical (921/931).
Regarding claim 76, Caballero teaches the composition further comprising Dorea longicatena, as discussed above.
Regarding claim 77, in view of the instant specification, instant SEQ ID NO: 5 represents Bacteroides fragilis and instant SEQ ID NO: 6 represents Anaerostipes caccae (see pg. 50, lines 15 and 33). As previously discussed, Caballero teaches embodiments that do not comprise a bacterial strain belonging to either species (see claim 1). Furthermore, none of the species recited in claim 1 of Caballero are disclosed as comprising a sequence having at least 97% sequence identity to instant SEQ ID NO: 5 or instant SEQ ID NO: 6. Thus, Caballero teaches embodiments wherein the composition does not comprise the claimed bacterial strains.
Regarding claim 79, Caballero teaches the composition wherein the bacterial strains are lyophilized (see claim 52).
Regarding claim 80, Caballero teaches a pharmaceutical composition comprising the composition comprising the bacterial strains (see claim 54). Caballero teaches the composition is formulated with an enteric coating that resists the action of gastric juices, and the enteric coating may consist of polymers (see pg. 76, lines 13-22). Caballero teaches that pharmaceutical preparations that allow for the delivery of the composition to the intestine include pH sensitive compositions, specifically, buffered sachet formulations or enteric polymers (see pg. 76, lines 29-31). Hence, Caballero teaches the composition is a pharmaceutical composition comprising a pH-sensitive composition comprising one or more enteric polymers.
Regarding claim 81, Caballero teaches the pharmaceutical composition can be in the form of a capsule (see pg. 76, lines 6-7).
Claim(s) 82-85 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gajewski et al. (WO 2018226690 A1; cited on Form 892), hereafter, “Gajewski”.
Regarding claim 82, Gajewski teaches a method of treating cancer in a human subject comprising administering to the subject an immune checkpoint inhibitor and a bacterial formulation comprising Collinsella aerofaciens and Bifidobacterium adolescentis (see claim 1).
Regarding claim 83, Gajewski teaches that examples of cancers that can be treated with the method include stomach cancer (see pg. 41, lines 10-13) and the cancer is selected from the group that includes stomach cancer (see pg. 5, line 29 and pg. 7, line 14). Examiner notes that the term “stomach cancer” refers to same condition as “gastric cancer” (see instant specification at pg. 1, line 21).
Regarding claim 84, Gajewski teaches the method comprises administering to the subject an immune checkpoint inhibitor, as discussed above.
Regarding claim 85, Gajewski teaches the method wherein the immune checkpoint inhibitor binds to an immune checkpoint protein (see claim 10) and wherein the immune checkpoint protein is PD-1, PD-L1, or CTLA-4 (see claim 11).
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) 78 is/are rejected under 35 U.S.C. 103 as being unpatentable over Caballero as applied to claims 66-77 and 79-81 above, and further in view of GenBank AP019724.1 2019 (cited on Form 892).
Regarding claim 78, Caballero teaches that multidrug resistant microorganisms have developed resistance to one or more classes of antimicrobial agents, such as antibiotics, and are emerging as a serious global health threat, with over 2 million people in the United States estimated to contract serious bacterial infections resistant to antibiotics each year (see pg. 1, lines 21-26). Caballero teaches compositions comprising bacterial strains which colonize the intestinal tract, thereby preventing or suppressing the colonization of multi-drug resistant organisms (see pg. 19, lines 4-16).
Caballero teaches a composition comprising purified bacterial strains of Collinsella aerofaciens, Bacteroides adolescentis, Faecalibacterium prausnitzii, and Bifidobacterium uniformis (see claim 1). As previously discussed, Caballero discloses strains of Collinsella aerofaciens, Bacteroides adolescentis, and Faecalibacterium prausnitzii comprising sequences sharing more than 99% sequence identity with instant SEQ ID NOs 1-3, respectively.
Caballero also discloses a strain of Bifidobacterium uniformis comprising a 16S rDNA sequence represented by SEQ ID NO: 47 (see pg. 100, line 1). However, Caballero’s SEQ ID NO: 47 (which has a length of 1474 base pairs) does not include the first 15 base pairs or the last 34 base pairs of instant SEQ ID NO: 20 (which has a length of 1523 base pairs). Hence, while the sequences share 99.7% local similarity (from residues 16 to 1489), Caballero’s SEQ ID NO: 47 shares less than 97% sequence identity compared to the full length of instant SEQ ID NO: 20.
GenBank AP019724.1 is identified as the complete genome of Bacteroides uniformis NBRC 113350 (see “DEFINITION”). As shown in the following alignment, the region of GenBank AP019724.1 spanning base pairs 1631792 to 1633314 (bottom) is more than 99% identical to the full-length of instant SEQ ID NO: 20 (top):
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Hence, GenBank AP019724.1 discloses a strain of Bacteroides uniformis comprising a sequence with more than 99% sequence identity to the full-length of instant SEQ ID NO: 20.
It would have been obvious at the time of filing for a person of ordinary skill to have arrived at the claimed invention by selecting the strain of Bacteroides uniformis disclosed in GenBank AP019724.1 for the composition taught by Caballero, because Caballero teaches that strains of Bacteroides uniformis are effective at colonizing the intestinal tract, thereby preventing or suppressing the colonization of multi-drug resistant organisms. One would have recognized that: (1) Caballero teaches embodiments that include selecting any strain of Bacteroides uniformis and the reference does not disparage or teach away from selecting any prior art strain; and (2) the GenBank sequence comprises a nearly identical sequence to that of Caballero’s SEQ ID NO: 47, which is identified as being derived from the same species. Thus, Caballero suggests a strain comprising a sequence that is highly similar to the GenBank sequence, and one would have been motivated to select this strain for a composition to prevent or suppress multi-drug resistant microorganisms. Accordingly, one could have substituted one known Bacteroides uniformis strain for another, and the results of the substitution would have been predictable. Hence, the combination would have been readily apparent and deemed to be a mere (B) simple substitution of one known element for another to obtain predictable results (see MPEP 2143(I): Rationales to support rejections under 35 U.S.C. 103).
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.
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Claims 66 and 68-72, 75-77 and 79-81 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 104-105, 107, 108 and 110-112 of copending Application No. 18/277,572 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they are anticipated by the reference claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 104 of ‘572 recites “A composition comprising:
(i) a purified bacterial strain comprising a 16S rDNA sequence with at least 97%
sequence identity to the nucleotide sequence of SEQ ID NO: 10;
(ii) a purified bacterial strain comprising a 16S rDNA sequence with at least 97%
sequence identity to the nucleotide sequence of SEQ ID NO: 29;
(iii) a purified bacterial strain comprising a 16S rDNA sequence with at least 97%
sequence identity to the nucleotide sequence of SEQ ID NO: 30; and
(iv) a purified bacterial strain comprising a 16S rDNA sequence with at least 97%
sequence identity to the nucleotide sequence of SEQ ID NO: 36.”
Claim 105 of ‘572 recites “The composition of claim 104, further comprising one or more additional purified bacterial strains, each of the additional purified bacterial strains comprising a 16S rDNA sequence with at least 97% sequence identity to a nucleotide sequence independently selected from SEQ ID NOs: 1-9, 11-28, 31-35, and 37-47.”
Claim 107 of ‘572 recites “A composition comprising:
(i) a purified bacterial strain belonging to the species Bacteroides faecis;
(ii) a purified bacterial strain belonging to the species Bacteroides vulgatus;
(iii) a purified bacterial strain belonging to the species Phascolarctobacterium faecium;
and
(iv) a purified bacterial strain belonging to the species Clostridium citroniae.”
Claim 108 of ‘572 recites “The composition of claim 107, further comprising one or more additional purified bacterial strains, each of the additional purified bacterial strains belonging to a species independently selected from the group consisting of Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Paeniclostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M clostridioforme, Eubacterium_E hallii, Agathobacter rectale, Blautia producta, Blautia_A obeum, Dorea longicatena, Coprococcus_B comes, Anaerostipes caccae, Agathobaculum sp, Escherichia coli, Fusobacterium_A sp, Bamesiella intestinihominis, Blautia luti, Blautiafaecis, Blautia wexlerae, Ruminococcusfaecis, Clostridium bolteae, Butyricimonas synergistica, Bilophila wadsworthia, Akkermansia muciniphila, Parasuterella excrementinihominis, and Prevotella copri.”
Claim 110 of ‘572 recites “The composition of claim 104, wherein the bacterial strains are lyophilized or spray-dried.”
Claim 111 of ‘572 recites “The composition of claim 104, wherein the composition comprises a pH-sensitive composition comprising one or more enteric polymers.”
Claim 112 of ‘572 recites “The composition of claim 104, wherein the composition is in the form of a capsule.”
Regarding instant claim 66, claims 107 and 108 of ‘572 recite a composition comprising purified bacterial strains belonging to the species Collinsella aerofaciens and Bifidobacterium adolescentis.
Regarding instant claim 68, claims 107 and 108 of ‘572 recite the composition further comprising Bacteroides thetaiotaomicron.
Regarding instant claim 69, claims 107 and 108 of ‘572 recite the composition further comprising Dorea longicatena.
Regarding instant claim 70, claims 107 and 108 of ‘572 recite Bacteroides fragilis and Anaerostipes caccae as being optional. Hence, the reference claims include embodiments wherein the composition does not comprise these species.
Regarding instant claim 71, claims 107 and 108 of ‘572 recite the composition further comprising Bacteroides uniformis.
Regarding instant claim 72, claim 105 of ‘572 recites SEQ ID NO: 1 which is identical to instant SEQ ID NO: 1, as shown in the sequence alignment data below:
PNG
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57
514
media_image12.png
Greyscale
Claim 105 of ‘572 recites SEQ ID NO: 34 which comprises a sequence that is 99.9% identical to the full length of instant SEQ ID NO: 2, as shown in the sequence alignment data below:
PNG
media_image13.png
56
516
media_image13.png
Greyscale
Examiner notes that while SEQ ID NO: 34 of ‘572 is longer than instant SEQ ID NO: 2, it comprises the full-length of the claimed sequence with only 1 base pair difference, hence comprising a sequence that is more than 99% identical (919/920) to the claimed sequence.
Regarding instant claim 75, claim 105 recites SEQ ID NO: 19 which shares more than 97% sequence identity to instant SEQ ID NO: 7, as shown in the sequence alignment data below:
PNG
media_image14.png
61
520
media_image14.png
Greyscale
Regarding instant claim 76, claim 108 of ‘572 teaches the composition further comprising Dorea longicatena.
Regarding instant claim 77, claim 105 of ‘572 does not require a sequence having at least 97% sequence identity to instant SEQ ID NO: 5 and/or instant SEQ ID NO: 6. Hence, the reference claims include embodiments wherein the composition does not comprise these species.
Regarding instant claim 79, claim 110 of ‘572 teaches wherein the bacterial strains are lyophilized or spray-dried.
Regarding instant claim 80, claim 111 of ‘572 teaches wherein the composition comprises a pH-sensitive composition comprising one or more enteric polymers.
Regarding instant claim 81, claim 112 of ‘572 teaches wherein the composition is in the form of a capsule.
Claims 67 and 73-74 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 104-105, 107-108, 110-112, 115 and 116 of copending Application No. 18/277,572 in view of Caballero (previously cited). This is an obvious-type rejection.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 115 of ‘572 recites “The composition of claim 104, wherein the composition is effective in suppressing colonization by a pathogenic organism in a subject.”
Claim 116 of ‘572 recites “The composition of claim 115, wherein the colonization is in an intestine of the subject.”
Regarding instant claim 67, claims 107 and 108 of ‘572 recite a composition comprising purified bacterial strains belonging to the species Collinsella aerofaciens and Bifidobacterium adolescentis. The reference claims do not teach the composition further comprising Faecalibacterium prausnitzii. However, as discussed under 35 U.S.C. 103, Caballero teaches compositions comprising bacterial strains which colonize the intestinal tract, thereby preventing or suppressing the colonization of multi-drug resistant organisms (see pg. 19, lines 4-16). As shown above, claims 115-116 of ‘572 relate to solving the same problem. As discussed under 35 U.S.C. 103, Caballero teaches that multidrug-resistant microorganisms are an emerging global threat. As the Caballero reference is in the same field of endeavor, and Caballero’s compositions are disclosed as solving the same problem as the reference claims, it would have been obvious for one to have combined these teachings with the motivation to suppress the colonization of pathogenic microorganisms in the intestine of a subject. As discussed under 35 U.S.C. 102, Caballero teaches the composition further comprising Faecalibacterium prausnitzii.
Regarding instant claim 73, Caballero teaches the composition comprising Collinsella aerofaciens, Bacteroides adolescentis, and Faecalibacterium prausnitzii which are disclosed as comprising sequences with more than 99% sequence identity to SEQ ID NOs 1-3, as discussed under 35 U.S.C. 102.
Regarding instant claim 74, Caballero teaches the composition comprising Collinsella aerofaciens, Bacteroides adolescentis, and Faecalibacterium prausnitzii which are disclosed as comprising sequences with more than 99% sequence identity to SEQ ID NOs 1-3, as discussed under 35 U.S.C. 102.
Claim 78 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 104-105, 107-108, 110-112, 115 and 116 of copending Application No. 18/277,572 in view of Caballero and GenBank AP019724.1 (previously cited). This is an obvious-type rejection.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding instant claim 78, as discussed under 35 U.S.C. 103, Caballero teaches that multidrug resistant microorganisms are emerging as a serious global health threat and discloses compositions comprising bacterial strains which colonize the intestinal tract, thereby preventing or suppressing the colonization of multi-drug resistant organisms. Caballero teaches a composition comprising purified bacterial strains of Collinsella aerofaciens, Bacteroides adolescentis, Faecalibacterium prausnitzii, and Bifidobacterium uniformis. As previously discussed, Caballero discloses strains of Collinsella aerofaciens, Bacteroides adolescentis, and Faecalibacterium prausnitzii comprising sequences sharing more than 99% sequence identity with instant SEQ ID NOs 1-3, respectively. However, Caballero does not disclose a sequence comprised by Bifidobacterium uniformis with at least 97% sequence identity to the nucleotide sequence of instant SEQ ID NO: 20. As discussed under 35 U.S.C. 103, GenBank AP019724.1 discloses a strain of Bacteroides uniformis comprising a sequence with more than 99% sequence identity to the full-length of instant SEQ ID NO: 20. Therefore, the instant claim would have been obvious for the same reasons discussed in the NSDP rejection of instant claim 67 above (in view of ‘572 and Caballero), as well as the reasons discussed in the rejection under 35 U.S.C. 103 (in view of Caballero and GenBank AP019724.1).
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