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 .
DETAILED ACTION
Applicant’s response filed on 02/20/2026 is duly acknowledged.
Claims 1-56 (including non-elected inventions of Groups I and II) were previously canceled by applicants.
Claims 87 and 88 have now been canceled by applicant’s current claim amendments.
Claims 110-116 have been newly presented by applicant’s current claim amendments.
Claims 57-86 and 89-116, as currently amended/presented, are pending in this application.
Claims 58 and 59 (non-elected Group IV) remain withdrawn.
Claims 64-82, and 95-109 (non-elected species) remain withdrawn.
Newly presented claims 113-116 (depend from previously withdrawn claims 95 and 102) are also withdrawn.
Claims 57, 60-63, 83-86, 89-94, and newly recited claims 110-112, as currently amended/newly presented (claims 57, 60-63, 83-86, 89-94 and 110-112 taken as elected Group III, without traverse; directed to “A method for treating, ameliorating, or reducing dysbiosis in a subject in need thereof....”) have been examined as they read on the elected species (a) of “an ATP-hydrolyzing enzyme”, hereinafter.
Priority
This application is a 371 of PCT/EP2021/065315 (filed on 06/08/2021), which claim foreign priority from a PCT/EP2020/065849 filed on 06/08/2020.
Claims
The claim term “dysbiosis” has been interpreted in light of applicant’s disclosure and definition(s) on record (see instant specification, p. 7-9, in particular).
Claim Objections- Withdrawn
In view of cancelation of claims 87-88, the claim objections as previously made by the examiner have been withdrawn.
Claim Rejections - 35 USC § 112 – Withdrawn
In view of current amendments to claims 57, 86, 90 and 91, the 112b rejections as previously made by the examiner, have been withdrawn.
Claim Rejections - 35 USC § 112 - WD Rejection - Withdrawn
In view of current amendments to claim 57, the 112(a) written description rejection of claims 57, 60-63 and 83-94, as previously made by the examiner, has now been withdrawn.
The following contains new grounds of objections/rejections necessitated by applicant’s current amendments to pending claims.
NOTE: 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.
Claim Rejections - 35 USC § 102 – Made/Maintained
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.
Claims 57, 60-62, 84-86, 89, 92-94 and 110 (as amended/newly presented) are/remain rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sevigny et al (WO 2018/058246 A1; FOR previously made of record) as evidenced by Toor et al (2019; NPL previously made of record).
Claim 57 (as currently amended) is directed to “A method for treating, ameliorating, or reducing dysbiosis in a subject in need thereof, comprising administering to the subject
(a) an ATP hydrolyzing enzyme,
(b) a nucleic acid comprising a polynucleotide encoding the ATP hydrolyzing enzyme,
(c) a host cell comprising the nucleic acid,
(d) a microorganism comprising the nucleic acid,
(e) a or
(f) a viral particle comprising the nucleic acid.”
See also limitations of the dependent claims 60-62, 84-86, 89, 92-94 and 110, as they pertain to applicant’s elected species (a) for “an ATP hydrolyzing enzyme”.
It is noted that instant claim 57 is a single step method claim that does not require any specific route of administration, and/or any specific therapeutic dose or dose regime for the treatment as claimed. Independent claim 57 is also not limited to any particular ATP hydrolyzing enzyme per se.
Sevigny et al (2018) teaches (regarding instant claim 57, as currently amended) treatment of inflammatory bowel disease (IBD, a dysbiosis-related disease; i.e. the subject necessarily having certain degree of “dysbiosis” of the gut resulting in IBD; see for evidence Toor et al 2019, NPL also relied upon in the 103a rejection discussed below, see Title and page 2, 2nd paragraph; and page 5, 1st paragraph) comprising administration of nucleoside triphosphate disphosphohydrolase (NTPDase; such as apyrase) to a mammal in need thereof (see Title, Abstract, claims 14-17, for instance); wherein the ATP hydrolyzing enzyme is an apyrase (regarding instant claims 60-62; see Sevigny et al, apyrase can be from plant such as potato; Table 1, pages 10 and 12; employs apyrase grade VII, a commercial purified enzyme preparation from Sigma, see [0068], [0084], for instance); wherein the apyrase is comprised in a pharmaceutical composition with a carrier buffer such as phosphate buffered saline, PBS (instant claims 84-85; see Sevigny et al, [0009]-[0010], [0028], for instance); wherein the administration of the composition comprising apyrase can be oral, enteral, or intrarectal, and in combination with a dysbiosis-inducing agent (regarding instant claims 86, 89, and newly recited claim 110; see Sevigny et al, claim 16, 3% w/v dextran sodium sulfate (DSS)-induced mouse colitis model shown in [0028], [0070], [0085], and claim 34, for instance); wherein the dysbiosis or dysbiosis-related disease is an inflammatory disease such as inflammatory bowel disease, or a gastrointestinal tract-related disorder such as colitis (see Sevigny et al, [0028], [0036], [00112], Figure 11, for instance); wherein the dysbiosis-inducing agent and/or the ATP hydrolyzing enzyme (4 U enzyme/mice in PBS) are administered repeatedly, together with, and/or after administration of the dysbiosis-inducing agent DSS (regarding instant claims 92-94; see Sevigny et al, [0028], [00102], Example 7 and Figure 11, for instance). Thus, Sevigny et al reasonably disclose all the limitations of the method claims 57, 60-62, 84-86, 89, 92-94 and 110 as currently amended/presented for treating, ameliorating or reducing intestinal dysbiosis or dysbiosis-related disease in a subject in need thereof.
As per MPEP 2111.01, during examination, the claims must be interpreted as broadly as their terms reasonably allow. In re American Academy of Science Tech Center, F.3d, 2004 WL 1067528 (Fed. Cir. May 13, 2004)(The USPTO uses a different standard for construing claims than that used by district courts; during examination the USPTO must give claims their broadest reasonable interpretation.). This means that the words of the claim must be given their plain meaning unless applicant has provided a clear definition in the specification. In re Zletz, 893 F.2d 319, 321, 13 USPQ2d 1320, 1322 (Fed. Cir. 1989).
Claim Rejections - 35 USC § 103- Made/Maintained
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 57, 60-63, 83-86, 89-94 and 110-112 (as amended/ newly presented) are/remain rejected under 35 U.S.C. 103 as being unpatentable over Sevigny et al (WO 2018/058246 A1; FOR previously made of record) when taken with Asalapuram et al (US 2017/0321196 A1; US-PGPUB previously made of record), Toor et al (2019; NPL previously made of record) and Shafer (2019; FOR cited as ref. [N] on PTO 892 form).
The detailed teachings and/or suggestions from Sevigny et al (as evidenced by Toor et al) as they pertain to method of instant claims 57, 60-62, 84-86, 89, 92-94 and 110 have been discussed above, and are further relied upon in the same manner hereinafter.
However, the method wherein the “ATP hydrolyzing enzyme” comprises an amino acid sequence as set forth in SEQ ID NO: 1 or a sequence variant thereof having at least 70%, 80% or 90% sequence identity thereto”; and wherein the “dysbiosis-inducing agent” is an antibiotic or a chemotherapeutic agent (see instant claims 63, 90-91, and newly recited claims 111-112 below) have not been explicitly taught by Sevigny et al, as discussed above.
Claims 63 and 111-112 (new) recited by applicants have been reproduced as follows:
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Asalapuram et al (2017) disclose a Shigella flexneri derived, ATP-hydrolyzing apyrase enzyme (see Title, Abstract, [0071], [0073]-[0075], for instance) that has an amino acid sequence (shown as SEQ ID NO: 4; termed rSFA; Figure 3B, for instance) that is 99.1% identical to instantly claimed apyrase enzyme of claim 63 (see homology below). Asalapuram et al also disclose the fact that apyrase enzyme obtained from Shigella flexneri was found to be more effective in hydrolyzing nucleotide di- and triphosphates, including ATP and other analogs, and therefore was more useful in detection and measurement of ATP in samples compared to commonly used apyrase enzyme obtained from potato plant (see [0095], for instance).
Sequence Homology Search (A_Genseq database for SEQ ID NO: 1):
RESULT 4
BDA20212
ID BDA20212 standard; protein; 259 AA.
XX
AC BDA20212;
XX
DT 30-JUN-2016 (first entry)
XX
DE Plasmid pBL-apyrase-6His clone derived protein, SEQ ID 4.
XX
KW apy protein; apyrase; degradation.
XX
OS Shigella flexneri 2a.
OS Synthetic.
OS Unidentified.
XX
CC PN WO2016071497-A1.
XX
CC PD 12-MAY-2016.
XX
CC PF 06-NOV-2015; 2015WO-EP075924.
XX
PR 07-NOV-2014; 2014SE-00051332.
XX
CC PA (APIR-) APIRAYS AB.
XX
CC PI Asalapuram P, Russom A;
XX
DR WPI; 2016-290324/37.
DR N-PSDB; BDA20211.
XX
CC PT Determining amount of ATP in sample, by providing sample which comprises
CC PT contaminating nucleoside diphosphates and/or triphosphates, reducing
CC PT amount of contaminating nucleoside diphosphates and/or triphosphates, and
CC PT analyzing sample.
XX
CC PS Claim 22; SEQ ID NO 4; 56pp; English.
XX
CC The present invention relates to a novel method for determining the
CC amount of adenosine triphosphate (ATP) in a sample. Also described are:
CC (1) a Shigella flexneri apyrase of SEQ ID NO: 4 (BDA20212); (2) a
CC polynucleotide encoding the apyrase; (3) a vector comprising the
CC polynucleotide operably linked to promoter; (4) a host cell comprising
CC the polynucleotide operably linked to a promoter capable of inducing the
CC expression of polynucleotide; (5) a method for producing a recombinant
CC apyrase; (6) an use of S. flexneri apyrase for degrading contaminating
CC nucleoside triphosphate or nucleoside diphosphate in an analytical method
CC ; and (7) a composition comprising S. flexneri apyrase. The present
CC sequence is a plasmid pBL-apyrase-6His clone derived protein comprising
CC S. flexneri apyrase, useful in the method for determining the amount of
CC ATP in a sample.
XX
SQ Sequence 259 AA;
Query Match 99.1%; Score 1266; Length 259;
Best Local Similarity 99.2%;
Matches 244; Conservative 1; Mismatches 1; Indels 0; Gaps 0;
Qy 1 MKTKNFLLFCIATNMIFIPSANALKAEGFLTQQTSPDSLSILPPPPAEDSVVFLADKAHY 60
||||||||||||||||||||||||||||||||||||||||||||||||:|||| ||||||
Db 4 MKTKNFLLFCIATNMIFIPSANALKAEGFLTQQTSPDSLSILPPPPAENSVVFQADKAHY 63
Qy 61 EFGRSLRDANRVRLASEDAYYENFGLAFSDAYGMDISRENTPILYQLLTQVLQDSHDYAV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 64 EFGRSLRDANRVRLASEDAYYENFGLAFSDAYGMDISRENTPILYQLLTQVLQDSHDYAV 123
Qy 121 RNAKEYYKRVRPFVIYKDATCTPDKDEKMAITGSYPSGHASFGWAVALILAEINPQRKAE 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 124 RNAKEYYKRVRPFVIYKDATCTPDKDEKMAITGSYPSGHASFGWAVALILAEINPQRKAE 183
Qy 181 ILRRGYEFGESRVICGAHWQSDVEAGRLMGASVVAVLHNTPEFTKSLSEAKKEFEELNTP 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 184 ILRRGYEFGESRVICGAHWQSDVEAGRLMGASVVAVLHNTPEFTKSLSEAKKEFEELNTP 243
Qy 241 TNELTP 246
||||||
Db 244 TNELTP 249
Toor et al (2019), while reviewing gut dysbiosis and its effects on the intestinal immune homeostasis and gastric diseases (see Title, Abstract), disclose the art-known fact that prolonged and uncontrolled use of antibiotics, dietary alterations, and chemotherapeutic drugs/agents significantly contribute towards changes in the gut microbiota, in particular for the colony index of sensitive strains known to release microbial content in the intestinal micromilieu, wherein such changes influence the composition of gut microbiota and may result in promoting gastric diseases (see Abstract; page 2, 1-2 paragraphs; Figure 1, for instances). Although, Toor et al do not disclose specifical dysbiosis-inducing agent(s), they nevertheless clearly provide the link between the use of antibiotics, dietary alterations, and/or chemotherapeutic agents and their effects on gut microbiota, and dysbiosis and related disorders in subjects using such agents.
Although, the specific antibiotics and/or chemotherapeutic agents that induce intestinal dysbiosis (see instant claims 90-91, and 111-112, as newly presented) have not been explicitly discussed by Toor et al, such dysbiosis-inducing agents (including vancomycin, metronidazole, cefoperazone, ampicillin, etc.; or the chemotherapeutic agents including 5-fluorouracil, 5-FU) were already well known and disclosed in the prior art (see the disclosure from the cited prior art of Shafer, 2019; see [003]-[004], [00148], and disclosure for 5-FU/vancomycin-induced IBD model disclosed at p. 70, [00285] paragraph).
Thus, given the detailed disclosure and suggestions from Toor et al (when taken with the disclosure from Shafer) and Asalapuram et al (see teachings/suggestions as discussed above), it would have been obvious to an artisan of ordinary skill in the art to modify the method taught by Sevigny et al such that it employs an apyrase (from Shigella flexneri; see disclosure from Asalapuram et al) that is found to be more efficient in hydrolyzing ATP and other related analogs when compared to other commonly used plant apyrases, especially in subjects that may have antibiotic or chemotherapeutic drug-induced alterations in the gut microbiota, i.e. with gut dysbiosis (and/or related disorders), as already suggested by Toor et al, including for treating subjects with gut dysbiosis that is induced by the use of antibiotics, and/or chemotherapeutic agents (agents that are already known to induce gut dysbiosis in subjects; see teachings from Shafer, as discussed above). Since, Asalapuram et al disclose the fact that recombinant Shigella flexneri apyrase is superior in catalytic/hydrolytic activity, an artisan of ordinary skill in the art would have been motivated to employ and make such modification successfully, and such would have been fully contemplated by an artisan of ordinary skill in the art, unless evidence/data provided on record to the contrary (which is currently lacking on record) commensurate with the scope of the invention as claimed.
Thus, the claim as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the invention as generically claimed.
Examiner’s Response to Arguments
Applicant’s arguments filed on 02/20/2026 with respect to claim(s) of record as currently amended/newly presented (see REM, pages 12-14, in particular) have been considered but are moot because the new grounds of rejections made in this office action as specifically discussed above. However, applicant’s main argument regarding the cited primary art of Sevigny et al has been responded to hereinafter.
Regarding the 102(a)(1) rejection over Sevigny et al, applicants argue the following:
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It is noted to applicants that just because the term dysbiosis has not been explicitly recited in the prior art, it does not necessarily make it inapplicable under 102. The cited reference of Sevigny et al discloses an species of the gut dysbiosis in the form of inflammatory bowel disease (IBD; see 102 rejection discussed above), wherein it is well known in the art (see evidentiary reference of Toor et al, also relied upon in the 103a rejection of record) that “The gut microbiota and mucosal immunity constantly interact with each other to maintain intestinal homeostasis. However, if this balance is disturbed, dysfunction of the intestinal immune system occurs that further triggers a variety of diseases including IBD” (see Toor et al, p. 5, 1st paragraph, for instance), and therefore a certain degree of gut dysbiosis is directly applicable to the subject having IBD. Thus, the cited reference of Sevigny et al still qualifies as a reasonable anticipatory prior art.
Applicants are advised to amend the scope of claim 57 in order to further the prosecution of this case in a meaningful manner.
Conclusion
NO claims are currently allowed.
Pertinent Prior Art:
1. Wang et al. (2019; NPL of record in IDS)- “The administration of Escherichia coli Nissle 1917 ameliorates irinotecan–induced intestinal barrier dysfunction and gut microbial dysbiosis in mice”, Life Sciences, 231 (2019) 116529 (disclose a topoisomerase I inhibitor that is widely used in treatment of colon cancer as a chemotherapeutics that is known to induce intestinal dysbiosis; see Title, Abstract, and Introduction).
2. Guo et al (2017; previously of record)- “Long-term use of ceftriaxone sodium induced changes in gut microbiota and immune system”, Scientific Reports 7:43035 (DOI: 10.1038/srep43035); Feb 21st 2017 (disclose the fact that long term use of a cephalosporin class of broad spectrum antibiotic ceftriaxone sodium induces gut dysbiosis and changes gut microbiota and immune system in subjects using said antibiotic; see Title, Abstract, and Introduction; page 2, 1st paragraph, for instance).
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SATYENDRA K. SINGH whose telephone number is (571)272-8790. The examiner can normally be reached M-F 8:00- 5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, LOUISE W HUMPHREY can be reached at 571-272-5543. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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SATYENDRA K. SINGH
Primary Examiner
Art Unit 1657
/SATYENDRA K SINGH/Primary Examiner, Art Unit 1657
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