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
The amendments, arguments, and declaration filed Apr. 1 and 2, 2026 are acknowledged and have been fully considered. Claims 1-7, 9-14, 16, and 18-25 are now pending and are now under consideration. Claims 8, 15, and 17 are cancelled; claims 1, 3, 7, 9, 10, and 16 are amended; claims 21-25 have been added.
OBJECTIONS/REJECTIONS WITHDRAWN
The rejection of claims 1-15 under 35 U.S.C. 112(a)/112 1st paragraph, lack of written description, is withdrawn in light of the claim amendments.
The rejection of claims 1-16 and 18-20 under 35 U.S.C. 112(b)/112 2nd paragraph is withdrawn in light of the claim amendments.
The rejection of claim 15 under 35 U.S.C. 112(d)/112 4th paragraph is moot, in light of the claim cancellation.
The rejection of claims 1-16, 19, and 20 under 35 U.S.C. 102(a)(1) is withdrawn in light of the claim amendments.
OBJECTIONS/REJECTIONS MAINTAINED
The rejections of claims 1-7, 9-14, 16, and 18-20 under 35 U.S.C. 103(a) are maintained as discussed below.
Claim Objections (New)
The claim set filed 04/01/2026 is objected to because the claim set does not present the claims in proper ascending order. Specifically, claim 22 is missing from the claim set, and two claims are numbered as claim 21. As such, the claim set does not comply with 37 C.F.R. 1.121.
For sake of clarity in this Office action only, the second of the two claims numbered 21 will be referred to as claim 22. However, in order to remedy this issue the second of the two claims numbered 21 and the subsequent claims (i.e., 23-25) should NOT merely be renumbered. In order to avoid confusion in the record, the claims starting with the second of the two claims numbered 21 and the subsequent claims (i.e., claims 23-25) should be cancelled and re-presented starting with claim number 26. Any amendment renumbering the second of the two claims numbered 21 and the subsequent claims (i.e., 23-25) without cancelling these claims and representing them as new claims will NOT be entered.
Claim Rejections - 35 USC § 112(b) or (pre-AIA ) 35 USC § 112 (2nd Par.)
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.
Claims 10-12 are rejected 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, or for pre-AIA the applicant regards as the invention.
Claims 10-12 depend, directly or indirectly, from a cancelled claim (i.e., claim 8). Accordingly, the metes and bounds of these claims cannot be ascertained and the claims are indefinite.
Claim Rejections - 35 USC § 103 (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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) 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 at the time any inventions covered therein were effectively filed 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 at the time a later invention was effectively filed 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 1-7, 9-14, 16, 19, 20, 22*, and 23 are rejected under 35 U.S.C. 103 as being unpatentable over ZHOU (CN 104817629; Pub. Aug. 5, 2015) in view of KIM (Kim, K.-H., et al. Biotechnol. Bioprocess Eng. (2001), 6; 244-251), LIN (WO 01/11077; Pub. Feb. 15, 2011; on IDS), and KAWAI (US 2013/0303619; Pub. Nov. 14, 2013).
*Claim 22 is missing from the claim set, and two claims are numbered 21. As set forth in the Claim Objections section above, the second of the two claims numbered 21 will be referred to as claim 22 for purposes of clarity in this Office action only. Note the remedy required to correct the mis-numbered claims in the Claim Objections section above.
Zhou discloses an antibacterial peptide having the exact amino acid sequence of instant SEQ ID NO:1 (See Zhou, title; abstract; SEQ ID NO:2). Zhou teaches the antibacterial peptide fragment is active against various pathogenic bacterial (abstract). Zhou teaches oral use of the peptide, which can be combined with an enamel adhesion peptide, for example, for use in preventing and treating dental plaque, caries, periodontal diseases and the like (abstract). Zhou does not appear to teach an amidated C-terminus or the use of the peptide to treat bowel disease, such as irritable bowel syndrome (IBS).
Regarding the C-terminal amidation of SEQ ID NO:1, this is a common strategy used by peptide chemists to improve stability and maintain activity of bioactive peptides. For example, Kim reports on the production of bioactive peptides and teaches that over half of all biologically active peptides are amidated at their C-terminus, which is essential for their full biological activities (title; abstract). Kim teaches that among post-translational peptide modifications, C-terminal amidation is known to be the most important and essential for biological activity (p. 244, 2nd col.; Table 1; p. 245, 2nd col.).
In light of these teachings, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used a C-terminally amidated version of the antibacterial peptide of Zhou. One would have been motivated to do so since C-terminal amidation is known in the art to improve stability (e.g., by protection from carboxypeptidases that require a free carboxylate (-COO-) at the C-terminus), and since C-terminal amidation is known to be required for full biological activity (per Kim).
Regarding the treatment of bowel diseases, such as IBS, the use of a known antibacterial peptide in the treatment of conditions like IBS that are characterized by overgrowth of bacteria would have been obvious to an ordinary artisan in light of the prior art.
For example, Lin discloses treatment of IBS and other disorders caused by small intestinal bacterial overgrowth (SIBO) (title; abstract). Lin teaches at least partially eradicating the SIBO condition by administration of anti-microbial agents, which can be any natural, synthetic, or semi-synthetic agent (abstract; p. 15, lines 9-17; p. 19, lines 12-15; claims 12-13). Thus, Lin discloses the concept of treating IBS with antibacterial agents.
Further, Kawai discloses antibacterial compositions for the treatment of oral/periodontal conditions as well as IBS (title; abstract; [0063]-[0064], [0067], [0176]; claim 8). Thus, Kawai links oral care to the treatment of irritable bowel syndrome. Kawai teaches the use of antibacterial peptides in treating these conditions ([0006]-[0007], [0064]).
In light of these teachings, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used the known antibacterial peptide of Zhou (or a C-terminally amidated version thereof) to treat bowel conditions such as IBS. One would have been motivated to do so since IBS is known to be characterized by SIBO, and since the art recognizes eradication of SIBO with antibacterial agents as a treatment for IBS. Indeed, doing so amounts to no more than simple substitution of one known element for another (i.e., the known antibacterial peptide of Zhou for the antibacterial agents of Lin) to obtain predictable results (i.e., the reduction of SIBO in IBS). Further, Kawai teaches the concept of treating oral/periodontal conditions or bowel conditions such as IBS with antibacterial compositions, specifically antimicrobial peptides.
Regarding claims 3-4, 8, 9, 11, and 12, Zhou teaches oral administration (abstract). Further, Lin teaches both oral and rectal administration (p. 19, line 18). Lin teaches rectal administration by enema (p. 19, line 34 to p. 20, line 2; claim 21).
Regarding claims 5-6, 14, 16, and 20, Lin teaches administration of probiotics and antibiotics (abstract; p. 20, lines 6-7 and 30-32; p. 24, lines 24-29; claims 12-13, 35-36). Lin teaches useful antibiotics include rifaximin (p. 19, line 17; claims 17, 37).
Regarding claim 10, Lin teaches administration by capsules (p. 20, lines 12-13; p. 33, lines 3-8).
Regarding claim 13, the enema solution of Lin reads on a solution for colonic irrigation.
Regarding claim 19, Lin teaches antibiotics including penicillin, tetracycline, cephalosporins, etc. (p. 19, lines 15-17; p. 24, lines 24-28; claims 17, 37).
Regarding claims 22 and 23, Kawai teaches enteral administration ([0183]).
Claims 1-7, 9-14, 16, 18-21, and 23 are rejected under 35 U.S.C. 103 as being unpatentable over ZHOU, KIM, LIN, and KAWAI, and further in view of LI (Li, W., et al. Prog. Polym. Sci. (ePub Aug. 2012), 38; 421-444).
The teachings of Zhou, Kim, Lin, and Kawai are presented supra, and are incorporated herein. The references do not teach pegylated peptides.
However, the PEGylation, covalent attachment of polyethylene glycol (PEG) polymers to therapeutic agents, is a conventional, well-known technique that results in a variety of advantages for the biomolecule attached to the PEG moiety.
For example, Li reports that PEGylation is one of the most promising techniques to improve the therapeutic effect of drugs (title; abstract). Li teaches that PEG-drug conjugates have several advantages: prolonged residence in body, decreased degradation by metabolic enzymes, reduction or elimination of protein immunogenicity, increased water solubility, decreased toxicity, etc. (p. 422, 1st col.; p. 423, 2nd col.; p. 442, 1st col.). Li teaches that PEGylation technologies are widely used in drug modification, with an ever-increasing range in proteins, peptides, oligonucleotides, and small organic molecules (p. 422, 2nd col.). Li teaches examples of commercially used PEG-peptide containing drugs (Fig. 5).
In light of these teachings, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have PEGylated the antibacterial peptide of Zhou. One would have been motivated to do so since PEGylation is known to confer numerous advantages to biomolecules including prolonged residence in body, decreased degradation by metabolic enzymes, reduction or elimination of protein immunogenicity, increased water solubility, decreased toxicity, etc. (p. 422, 1st col.; p. 423, 2nd col.; p. 442, 1st col.).
Claims 1-7, 9-14, 16, and 19-25 are rejected under 35 U.S.C. 103 as being unpatentable over ZHOU, KIM, LIN, and KAWAI, and further in view of BORODY (US 2021/0000806; priority to 03/23/2018).
The teachings of Zhou, Kim, Lin, and Kawai are presented supra, and are incorporated herein. As noted above, Kawai teaches enteral administration. However, Borody is further cited to emphasize the obviousness of enteral administration for treatment of IBS.
Borody discloses compositions and methods for treating inflammatory bowel disease (including IBS) and other bacteria-caused related diseases and conditions (title; abstract; [0005], [0007], [0078]; claim 1). Borody teaches antimicrobials/antibiotics including tetracyclines, penicilins, and rifaximin as an active ingredient that may be used in combination with other antibiotics, including peptide antibiotics (abstract; [0005], [0012]-[0015]; claim 3). The compositions may additionally comprise probiotics ([0010], [0050], [0080]; claim 30). Borody teaches enteral formulation ([0037]; claim 33). Borody also teaches delayed release compositions comprising a gastro-resistant coating designed to dissolve in the terminal of the ileum ([0035]; claim 31).
In light of these teachings, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer a known antibiotic peptide enterally to treat IBS, a condition known to be caused by bacterial overgrowth. Doing so amounts to no more than simple substitution of one known element for another (i.e., the known antibacterial peptide of Zhou for the antibacterial agents of Lin) to obtain predictable results (i.e., the reduction of SIBO in IBS). It would additionally be obvious to use a delayed release dosage form (such as a coated tablet or capsule) to allow delivery/targeting to a specific region of the intestine, such as the ileum.
Claims 1-7, 9-14, 16, and 19-25 are rejected under 35 U.S.C. 103 as being unpatentable over ZHOU, KIM, LIN, and KAWAI, and further in view of LIN II (US 2002/0039599; Pub. Apr. 4, 2002).
The teachings of Zhou, Kim, Lin, and Kawai are presented supra, and are incorporated herein. As noted above, Kawai teaches enteral administration. However, Lin II is further cited to emphasize the obviousness of enteral administration for treatment of IBS.
Lin II discloses methods of treating SIBO and related conditions including IBS (title; abstract; [0008], [0074]). Lin II teaches antibiotics including penicillin, tetracycline, and rifaximin as an antimicrobial that may be used in combination with other antibiotics to reduce bacterial overgrowth ([0193]). Probiotics may additionally be used ([0196]-[0197]). Lin II teaches the use of peptides in conjunction with other active agents ([0143], [0145]; claim 9). Lin II teaches oral or enteral delivery ([0143], [0162]). Lin II teaches solid dosage forms (e.g., tablets, capsules) that may be coated to delay disintegration and absorption in the gastrointestinal tract and provide sustained release ([0161]-[0163], [0182], [0184]; claims 17-18).
In light of these teachings, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer a known antibiotic peptide enterally to treat IBS, a condition known to be caused by bacterial overgrowth. Doing so amounts to no more than simple substitution of one known element for another (i.e., the known antibacterial peptide of Zhou for the antibacterial agents of Lin) to obtain predictable results (i.e., the reduction of SIBO in IBS). Lin II teaches both oral and enteral administration routes for the treatment of IBS. It would additionally be obvious to use a delayed release dosage form (such as a coated tablet or capsule) to allow sustained delivery/targeting to a specific region of the intestine, such as the ileum.
Response to Arguments
Applicants' arguments have been fully considered but are not persuasive. Applicants argue that the peptides of Zhou are intended to bind the tooth surface (response, pgs. 7-8).
As applicants admit, Zhou discloses the exact same peptide sequence instantly claimed (i.e., KKVVFWVKFK, instant SEQ ID NO: 1) as a broad spectrum antibacterial peptide. Lin discloses treatment of IBS and other disorders caused by small intestinal bacterial overgrowth (SIBO). Using a known antibacterial to treat a condition known to be caused by bacterial overgrowth is not inventive. See MPEP § 2144.07. The selection of a known material based on its suitability for its intended use is prima facie obvious.
It is acknowledged that Zhou focuses on binding the disclosed antibacterial peptide to tooth surfaces. However, this teaching does not negate the fact that the exact same peptide sequence instantly claimed is known in the prior art as a broad spectrum antibacterial peptide, separate from its tooth binding fragment. Artisans in the field of bioactive peptides understand that the active portions of peptides can be, and are routinely, repurposed to other applications. Zhou discloses the KKVVFWVKFK peptide fragment as having broad spectrum antibacterial activity in and of itself. In order to add the tooth surface binding activity, the disclosed antibacterial peptide is conjugated to a hydroxylapatite binding peptide fragment. There is no indication that tooth surface binding is required for antibacterial activity. Further, Zhou teaches that this antibacterial peptide is capable of being connected to a hydroxylapatite binding fragment. This teaching itself implies that the antibacterial peptide could be used in other antibacterial applications that do not require tooth surface binding.
Applicants argue that removing the hydroxyapatite-binding peptide fragment from Zhou would render it unsatisfactory for its intended purpose (response, p. 8).
The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). In this case, Zhou is cited for the disclosure that the same peptide instantly claimed is known as a broad-spectrum antibacterial agent. Knowing that the claimed peptide has broad-spectrum antibacterial activity, an artisan would find it obvious to use such a broad-spectrum antibacterial in applications in which reduction of bacterial growth is desired. IBS is one such condition since it is known to be caused by small intestinal bacterial overgrowth (SIBO). While the hydroxyapatite-binding peptide fragment may be required for long term treatment in the oral cavity, using the antibacterial peptide fragment without the tooth surface-binding peptide fragment as a treatment in the oral cavity is NOT what is suggested in the rejection. Rather, the references presented in the rejection are cited for the premise that using any known antibacterial peptide to treat a condition known to be caused by bacterial overgrowth is prima facie obvious.
Applicants argue that the peptides of Zhou would require a means to adhere to the gastric lining to be effective (response, p. 8).
There is no indication that binding to any type of surface (tooth or otherwise) is required for antibacterial activity. To the contrary, Zhou teaches that the KKVVFWVKFK peptide fragment itself has broad-spectrum antibacterial activity. A hydroxyapatite-binding peptide fragment is only used to improve residence time, and prevent dilution in the oral cavity. A requirement for gastric lining adherence for antibacterial activity is unsupported speculation on the part of applicants.
Applicants argue that oral care and IBS are not particularly linked. Applicants provide a declaration by one of the instant inventors in support of this argument (response, p. 9; Declaration, par. 14).
At par. 14, the declaration provides a statement by the declarant expressing disagreement, and an unsupported statement that “It is not recognized that oral care and irritable bowel syndrome are particularly linked”. These statements do not refute the fact that Kawai shows, in the same field of endeavor as Zhou and Lin (i.e., antibacterial treatments of the alimentary tract), artisans would have understood that antibacterial treatments are known to be useful for the treatment of either conditions of the oral cavity or the intestinal tract. Kawai establishes this fact by disclosing antibacterial compositions (including antimicrobial peptides) that are useful for the treatment of oral/periodontal conditions and IBS (title; abstract; [0063]-[0064], [0067], [0176]; claim 8). Because Kawai establishes antibacterial treatments can be useful for both oral care and the treatment of irritable bowel syndrome, it would not be a stretch for an artisan in this field to use the known antibacterial peptide of Zhou for the treatment of an intestinal condition like IBS that is caused by SIBO.
Further regarding the declaration of inventor Paricha, the declarant presents an opinion on the legal conclusion of obviousness (e.g., declaration, par. 5), which is not given weight in the analysis of the declaration. That applicants may have been the first to present data of the claimed peptide (e.g., declaration, par. 6) in IBS is not probative. Applicants are reminded that the instant rejection is made under USC § 103, obviousness, not anticipation. Further, the data presented in par. 6 of the declaration are 1) not commensurate in scope with the instant claims (which do not even recite amounts administered, to which the data are limited) and 2) do not set forth the statistical significance of the data points presented. Regarding pars. 7-8 of the declaration, enteral delivery of therapeutic agents in IBS is not inventive as evidenced by Kawai, Borody, and Lin II. Declaration pars. 9-14 simply point out the deficiencies of the individual references cited. In response to declarant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Regarding par. 14 of the declaration, declarant references par. [0044] of the instant specification, and states, “as discussed above and at [0044] of the published present application, our results show that an antimicrobial peptide can be degraded rapidly in the stomach and thus indicate that an oral care agent as proposed in the Office Action would not be suitable for treatment of irritable bowel syndrome”. This statement is perplexing because several of the instant claims (e.g., claims 3, 9, and 10) require oral delivery. Likewise, claims 1, 2, 5-7, 13, 14, 16, and 18-20 embrace oral administration, and none of these claims place any limitation on the stability or special formulation of the peptide to be delivered through the stomach. Applicant's statement in par. 14 of the declaration and par. [0044] of the specification appear to raise written description and/or enablement issues with at least claims 1-3, 5-7, 9, 10, 13, 14, 16, and 18-20.
Finally, it is noted that applicants place a considerable amount of emphasis on Zhou's use of a tooth surface-binding peptide fragment throughout the response. Zhou was cited as the primary (first) reference since it seemed the most relevant inasmuch as Zhou discloses the exact same peptide sequence instantly claimed (i.e., KKVVFWVKFK, instant SEQ ID NO: 1) as a broad spectrum antibacterial peptide. However, the rejection would be equally valid if Zhou was used as a secondary reference. For example, Lin could equally well be cited first (i.e., used as the “primary” reference) for its disclosure of the concept of treating IBS with antibacterial agents. Since Zhou clearly discloses applicants' claimed peptide sequence as a broad-spectrum antibiotic peptide, it would be prima facie obvious to use a known antibiotic (from Zhou's disclosure, even as a secondary reference) to treat a condition known to be treatable with antibiotics such as IBS caused by SIBO. It is further noted that changing the order of references in a § 103 rejection is not considered a new ground of rejection before the Patent Trial and Appeal Board.
Summary/Conclusion
Claims 1-7, 9-14, 16, and 18-25 are objected to; claims 1-7, 9-14, 16, and 18-25 are rejected; claims 8, 15, and 17 are cancelled.
Applicants' 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 extension fee 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 date of this final action.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kevin S Orwig whose telephone number is (571)270-5869. The examiner can normally be reached Mon.-Fri. 7AM-4PM (with alternate Fridays off). If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Patricia Engle can be reached Mon.-Fri. at (571)276660. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Kevin S Orwig/Primary Examiner, Art Unit 3991
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