DETAILED ACTION
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
Claims 1-3, 5-10, 12-15, 17, 18, 21, 24, 28, 29 and 33 are pending.
Claims 1, 2, 8, 9 and 33 are examined herein.
Claims 3, 5-7, 10, 12-15, 17, 18, 21, 24, 28 and 29 are withdrawn (see restriction/election below).
Priority
This application is filed 03/26/2024, and claims the benefit of domestic priority as below:
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Information Disclosure Statements
One IDS(s) received on 1/14/2025 has been considered unless marked with a strikethrough.
Election/Restrictions
Applicant elects Group I, claims 1-3, 5-10, 12-14 and 33, is drawn to an antimicrobial compounds and compositions, with traverse in the reply field on 07/01/2026 is acknowledged. Claims 15, 17, 18, 21, 24, and 28-29 (Group II) are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a method of treating/using a fungal infection or a biofilm produced from a fungal infection, there being no allowable generic or linking claim.
The applicants argue that the restriction is improper for the following reasons: 1) While some additional review may be necessary, the scope of the novelty analysis for all claims in Group II must be conducted just as rigorously as when examining only the claims of Group I, therefore, it would not impose an undue burden on the examiner. 2) If the restriction requirement is applied to the claims of Group I and Group II, it would result in an excessive burden, as the applicant would not only have to pay separate additional application fees for the examination of the non-elected claims but also bear the costs associated with prosecuting two applications and maintaining three patents.
Applicant’s argument has been considered, but is not persuasive. This application contains Group I and II, which are not so linked as to form a single general inventive concept under PCT Rule 13.1. Although, the claims in Group I and II may share the general objective of treating or preventing a fungal infection or biofilm associated with a fungal infection, that objective does not constitute a “special technical feature” within the meaning of PCT rule 13.2. The treatment or prevention of fungal infections and fungal biofilms in the present case is already known in the art, and therefore does not provide the technical contribution necessary to link the claims of Group I and II. Instead, the claims of Group I and II rely on different technical features, mechanisms, compositions, treatment methods, or claimed subject matter to achieve the stated objective. Those distinguishing features are not shared between the groups. (see PCT rules 13.1 and 13.2)
In addition, examination of inventions lacking unity may impose an undue search burden because unlinked technical relationship requires separate prior art searches, different search classification, distinct claim constructions, and separate analyses of novelty, invention step, written description support, enablement, and claim clarity.
Lastly, Applicant’s financial and administrative burden also does not overcome the lack of unity.
Accordingly, Groups I and II are not linked by a single general inventive concept under PCT Rule 13.1/13.2, and the restriction requirement is deemed proper and is made FINAL.
Applicant elects the one compound, 911-M12 (Fig 7) as the species, with traverse in the reply field on 07/01/2026 is acknowledged.
If the elected specie is not identified in the prior arts, the elected specie would be allowable if
an independent claim were drafted with that specie alone. (see MPEP 802.03)
The elected specie was not identified in the art. If Applicant drafted an independent claim drawn to only the elected specie that claim would be allowable. Examiner expanded his search to a new specie pursuant to MPEP 803.02. The expanded specie reads on claims 1, 2, 8, 9 and 33 in Group I. (see 35 USC 102 below and MPEP 818) Claims 3, 5-7, 10, and 12-14 are withdrawn as not reading on the expanded specie. It should be noted that the full scope of claims 3, 5-7, 10, and 12-14 have not yet been searched.
Accordingly, claims 1, 2, 8, 9 and 33 will be examined on their merits. With respect to the expanded species, the art is rejected under 35 USC 112(a), 35 USC 102 and 35 USC 103 below.
Claim interpretation
Claims are interpreted in accordance with the broadest reasonable interpretation (BRI) standard
consistent with the specification (See MPEP 2111).
Claims 1 and 8 define that recites “R10NR11R12R13 each R11, each R12, and each R13 are independently H or (C1 to C6)alkyl” that do not encompass a terminal primary amine. However, for purposes of examination and in view of the specification, the limitation “R10NR11R12R13” in claims 1 and 8 is interpreted as encompassing aminoalkyl substituents having a terminal primary amine, including Nlys, Nap and Nae.
Claim Rejections - 35 USC § 112, 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.
Claim 33 is 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.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by applicants. (see MPEP 2163.02)
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), to satisfy the written description requirement, an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention, and that the invention, in that context, is whatever is now claimed. (Emphasis added)
Further, the MPEP states that for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. (see MPEP 2161.01)
For instance, generic claim language in the original disclosure does not satisfy the written description requirement if it fails to support the scope of the genus claimed. Ariad, 598 F.3d at 1349-50, 94 USPQ2d at 1171 ("[A]n adequate written description of a claimed genus requires more than a generic statement of an invention’s boundaries.") (citing Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1405-06); Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002) (holding that generic claim language appearing in ipsis verbis in the original specification did not satisfy the written description requirement because it failed to support the scope of the genus claimed); Fiers v. Revel, 984 F.2d 1164, 1170, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993) (rejecting the argument that "only similar language in the specification or original claims is necessary to satisfy the written description requirement").
As set forth in the en banc decision in Ariad Pharmaceuticals Inc. v. Eli Lilly and Company, 94 USPQ2d 1161 (Fed. Cir. 2010) at 1171, the court stated as follows:
We held that a sufficient description of a genus instead requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can “visualize or recognize” the members of the genus. Id. At 1568-69. We explained that an adequate written description requires a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials. Id. At 1568 (quoting Fiers v. Revel, 984 F.2d 1164, 1171 [25 USPQ2d 1601] (Fed. Cir. 1993)). We have also held that functional claim language can meet the written description requirement when the art has established a correlation between structure and function. See Enzo, 323 F.3d at 964 (quoting 66 Fed. Reg. 1099 (Jan. 5, 2001)). But merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species.
With respect to claim 33, the claim recites that “the compound of claim 1 wherein a second minimum inhibitory concentration is no greater than a 200% of a first minimum inhibitory concentration, wherein the first minimum inhibitory concentration is evaluated without a serial gain of resistance assay against a microbe of interest, and the second minimum inhibitory concentration is evaluated after the serial gain of resistance assay against the microbe of interest.”
The specification provides a serial passage result for RGM9-11 against Candida albicans in Example 1 and Table 3. Specifically, the MIC od RMG9-11 against Candida albicans was 6.25 ug/mL both without serial passage and after serial passage in the presence of increasing sub-MIC concentration of PMG9-11 (table 3). However, claim 33 encompasses the structurally diverse genus of peptoid compounds recited in claim 1 when used against any “microbe of interest”. Thus, the claim is not limited to RMG9-11, to Candida albicans, or to the particular compound microbe combination tested in the specification. The specification provides no serial passage data showing that other structurally distinct compounds within the genus satisfy the claimed MIC limitation, and it provides no such data for other fungal or bacterial microbes encompassed by the phrase “a microbe of interest”.
Mojsoska et al. (Structure-activity relationship study of novel peptoids that mimic the structure of antimicrobial peptides, Antimicrobial Agents and Chemotherapy, 59(7), 4112-20, pub’d 05/04/2015) discloses that changes in peptoid structure, hydrophobicity, and amphipathicity can materially affect antimicrobial activity (introduction). In addition, Samuelsen et al. (Induced resistance to the antimicrobial peptide lactoferricin B in Staphylococcus aureus, FEBS Lett, 579(16), 3421-6, pub’d 05/31/2005) teaches resistance developed during serial passage may be among microbial strains (abstract). In view of Mojsoska and Samuelsen, the post passage MIC property recited in claim 33 is not predictable from the general peptoid structure or from the result obtained for a single compound microbe combination.
In view of such unpredictability taught by Mojsoska and Samuelsen, a person of ordinary skill in the art would not recognize that the inventors had possession the full scope of the compounds of claim 1 that satisfy the claimed post-passage MIC limitation against the full scope of microbes encompassed by claim 33 at the time of filing. The specification does not provide a representative number of structurally varied compounds satisfying the claimed MIC limitation, nor does it identify structural features that correlate with that function.
As set forth in the en banc decision in Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010), to satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention at the time of filing. Specifically, the specification must describe the claimed invention in a manner understandable to a person of ordinary skill in the art in a way that shows that the inventor actually invented the claimed invention at the time of filing. Id.; Ariad, 598 F.3d at 1351, 94 USPQ2d at 1172. (see MPEP 2161.01).
Accordingly, in view of the breadth of the claimed combinations, the breadth of the term “a microbe of interest”, the disclosure of serial passage results for only one compound-microbe combination, and the unpredictability of the relationship between peptoid structure, microbial strain, and acquired resistance, the specification does not reasonably convey to those skilled in the art that the inventors are in possession of the full scope of claimed combination therapies at the time of filing.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
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.
The rejections under this section are made when the scope of the claimed subject matter is not clear. (See MPEP 2173)
Claims 2 and 9 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.
Claims 2 and 9 recites the limitation "Nlys, Nap, and Nae" in the body of claims 2 and 9. There is insufficient antecedent basis for this limitation in the claim. Claims 1 and 8 recite “R10NR11R12R13 each R11, each R12, and each R13 are independently H or (C1 to C6)alkyl” that do not encompass R10NH2 for Nlys, Nap, and Nae. Dependent claims 2, and 9 do not add a further limitation to the subject matter of their independent claims 1 and 8.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 2, 8 and 9 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Barron et al. (US 2012/0295838 A1, pub'd 11/22/2012).
With respect to claims 1 and 2, Barron teaches the six residue peptoid C10-16mer having the structure dec-(Nlys-Nspe-Nspe)2-NH2 (Barron's Specification, pg. 7 table 2). This compound has a C10 linear alkyl terminal substituent, six N-substituted glycine residues comprising Nlys and Nspe side chains, and an amide C-terminal (Barron's Specification, pg. 7 table 2). Accordingly, the disclosed compound falls within the compound genus recited in claims 1 and 2.
With respect to claims 8 and 9, Barron teaches pharmaceutical compositions comprising one or more of the compound of its poly-N-substituted glycine compounds and a pharmaceutically acceptable carrier (paragraph [0013] and [0021]). Because Barron identifies C10-16mer as one of its poly-N-substituted glycine compounds, Barron’s disclosure of a pharmaceutical composition comprising such a compound and a pharmaceutically acceptable carrier reads on the composition recited in claim 8. Further, because the Nlys and Nspe residues of C10-16mer fall within the side chain alternatives recited in claim 9.
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(Instant Formula in claim 1)
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Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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.
This rejection is separate from and cumulative to the rejection under 35 USC 102. 35 USC 102 rejection relies on a specifically disclosed species within the claimed genus, whereas 35 USC 103 rejection relies on the prior art’s teachings concerning the predictable selection and substantiation of other known alternative peptoid residues.
Claim(s) 1, 2, 8, and 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Barron et al. (US 2012/0295838 A1, pub'd 11/22/2012), in view of Bicker (US2020/0188354 A1, pub'd 06/18/2020, IDS cited), and further in view of Chongsiriwatana et al. (Peptoids that mimic the structure, function, and mechanism of helical antimicrobial peptides, Proc. Natl. Acad. Sci. U. S. A., 105(8), 2794-9, pub'd 02/19/2008).
With respect to independent claim 1, the claim recites that a compound of the general formula, a protonated form thereof, a pharmaceutically acceptable salt thereof, or both, having a diversity of N-substituted residues.
Barron teaches that 1)antimicrobial poly-N-substituted glycine compounds (i.e., antimicrobial peptoids), having a six residue peptoid backbone and comprising combinations of cationic and hydrophobic side chains (paragraph [0039], [0075], and [0082]); 2) such six-mer peptoids show antimicrobial activity and arrangement of the side chain residues may be modified to alter their biological properties (paragraph [0039], and [0043]); and 3) the antimicrobial activity and selectivity of peptoids are affected by their cationicity, hydrophobicity, amphipathicity, and residue arrangement (table 2, paragraph [0046], and [0058]).
Barron fails to teach every alternative recited for R1-R6 or the claimed linear C13 alkyl terminal group.
Bicker teaches that 1) antimicrobial peptoids comprising a hydrophobic terminal group, including a linear tridecyl, or C13 alkyl group (abstract and ACE 5 compound); 2) the hydrophobic terminal group is a pharmacologically important structural feature affecting antimicrobial or antifungal potency and mammalian cell toxicity (paragraph [0069]); 3) an iterative structure activity optimization process in which the terminal hydrophobic group and individual aromatic, heterocyclic, hydrophobic, and cationic peptoid residues are varied, and resulting compounds are evaluated for minimum inhibitory concentration, mammalian cell toxicity, and selectivity ratio (paragraph[0042], [0068]-[0072], and Figure 1-7);
The combination teachings of Barron and Bicker fail to teach the specific relationship between the cationic and hydrophobic residues and the resulting antimicrobial potency, mammalian cell toxicity, and microbial selectivity.
Chongsiriwatana teaches that antimicrobial peptoid activity and selectivity depend on net cationic charge and hydrophobicity (introduction, Structure–Activity Studies, and discussion section). Chongsiriwatana explains that cationic residues promote association with negative charged microbial membranes, while aromatic and other hydrophobic residues facilitate membrane insertion and disruption (discussion section). Chongsiriwatana further teaches that hydrophobicity may increase nonspecific interaction with mammalian cell membranes and reduce selectivity (Ampetoid Selectivity Evaluated by Using Cultured Mammalian Cells, and discussion section). Accordingly, the identities, numbers, and positional arrangement of the cationic, aromatic, and hydrophobic residues are known result-effective variables for controlling antimicrobial potency, mammalian cell toxicity, and microbial selectivity.
It would have been obvious to a PHOSITA at the time of the invention to introduce the linear C13 alkyl terminal group proposed by Bicker into Barron’s antimicrobial six-mer peptoid and to modify the known cationic, aromatic, heterocyclic, and hydrophobic residues at positions R1 through R6 in accordance with the teachings regarding structure-activity relationships presented by Barron, Bicker, and Chongsiriwatana. A person of ordinary skill in the art would have been motivated to make such modifications to improve antimicrobial or antifungal efficacy, reduce mammalian cytotoxicity, and enhance selectivity by optimizing the existing effects associated with cationic, hydrophobic, and amphiphilic properties and residue distribution. Because peptoids are known to be modular oligomers assembled from selectable N-substituted glycine building block, the skilled artisan would have had a reasonable expectation that the claimed residue alternatives could be incorporated into Barron’s known six-mer backbone and that at least some of the resulting compounds would retain or improve antimicrobial activity and selectivity. For example, compound 911-M1 contains a hydrophobic N terminal C13 alkyl group and shows improved antifungal activity and selectivity compared with the compound RMG9-11. In addition, 911-M2 which contains an additional cationic N-substituted residue, shows reduce mammalian cytotoxicity, although its antifungal activity is somewhat reduced. Accordingly, the proposed combination would have been expected to provide the recognized advantages of improved potency, reduced toxicity, and enhanced microbial selectivity, and the variations are known result-effective variables for controlling antimicrobial potency, mammalian cell toxicity, and microbial selectivity. (see MPEP 2144.05)
The references is directed to the same field of endeavor and address related to the application. The Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham.
Examples of rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Consistently, applying KSR example rationale (D) in the independent claim 1, it would have been prima facie obvious to apply the structure activity relationships (SARs) of known peptoid optimization techniques taught by Bicker, and Chongsiriwatana to Barron’s known antimicrobial six-mer peptoid scaffold, yielding predictable improved antimicrobial or antifungal potency, reduced mammalian cell toxicity, and enhanced microbial selectivity. (see MPEP 2141)
With respect to claim 2, the claim 2 recites a narrower alternatives recited for N-substituted residues for R1-R6.
The combination teachings of Barron, Bicker, and Chongsiriwatana teach using such residue classes to provide positive charge, hydrophobicity, amphipathicity, membrane association, and membrane disruption. The rationale is the same as that for independent claim 1.
With respect to claims 8 and 9, the claim 8 recites a composition comprising a compound of the general formula, or a protonated form thereof, and the claim 9 recites a narrower alternatives recited for N-substituted residues for R1-R6.
Barron teaches pharmaceutical compositions comprising one or more of the compound of its poly-N-substituted glycine compounds and a pharmaceutically acceptable carrier (paragraph [0013] and [0021]). Because Barron identifies C10-16mer as one of its poly-N-substituted glycine compounds, Barron’s disclosure of a pharmaceutical composition comprising such a compound and a pharmaceutically acceptable carrier reads on the composition recited in claim 8. In addition, the combination teachings of Barron, Bicker, and Chongsiriwatana teach using such residue classes to provide positive charge, hydrophobicity, amphipathicity, membrane association, and membrane disruption. The rationale is the same as that for independent claim 1.
Claim(s) 33 is/are rejected under 35 U.S.C. 103 as being unpatentable over Barron et al. (US 2012/0295838 A1, pub'd 11/22/2012), Bicker (US2020/0188354 A1, pub'd 06/18/2020, IDS cited), and Chongsiriwatana et al. (Peptoids that mimic the structure, function, and mechanism of helical antimicrobial peptides, Proc. Natl. Acad. Sci. U. S. A., 105(8), 2794-9, pub'd 02/19/2008) as applied to claim 1 above, and further in view of Thappeta et al. (Combined Efficacy of an Antimicrobial Cationic Peptide Polymer with Conventional Antibiotics to Combat Multidrug-Resistant Pathogens, ACS Infect. Dis., 6(5), 1228-1237, pub'd 03/13/2020) .
With respect to claim 33, the claim 33 recites a second minimum inhibitory concentration is no greater than a 200% of a first minimum inhibitory concentration, wherein the first minimum inhibitory concentration is evaluated without a serial gain of resistance assay against a microbe of interest, and the second minimum inhibitory concentration is evaluated after the serial gain of resistance assay against the microbe of interest.
The combination teachings of Barron, Bicker, and Chongsiriwatana are discussed above.
The combination teachings fail to teach a peptoid for which the MIC measured after a serial gain of resistance assay is no greater than a 200% of a first minimum inhibitory concentration.
Thappeta teaches evaluating a synthetic cationic membrane active antimicrobial by serially passing microorganisms in sub-inhibitory concentrations (abstract). Thappeta further teaches after repeated passage, the tested organisms exhibited no more than a two-fold increase in MIC (CSM5-K5 Exposure Does Not Result in Antimicrobial Resistance, and Combination Treatment of CSM5-K5 with Conventional Antibiotics against MDR Clinical Isolates Restores Drug Sensitivity section). Thus, Thappeta discloses both the claimed type of resistance assay and the recognized advantage of selecting antimicrobial compounds that retain activity and have a reduced propensity to induce microbial resistance.
It would have been obvious to a PHOSITA at the time of the invention to apply the serial passage screening and selection technique taught by Thappeta to the antimicrobial six-mer peptoids rendered obvious by Barron, Bicker, and Chongsiriwatana, and select compounds exhibiting no more than a two-fold increase in MIC, in order to obtain the advantage of sustained antimicrobial efficacy after repeated microbial exposure and a reduced of resistance development. Given that the serial passage MIC test is a well-known method for evaluating the development of resistance and that Thappeta demonstrated that synthetic cationic membrane-active antimicrobial agents could maintain substantially unchanged MIC values after repeated passages, a person skilled in the art would have had a reasonable expectation of successfully identifying such compounds.
Conclusion
Claims 1, 2, 8, 9 and 33 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEONG JONG KIM whose telephone number is (571)272-6918. The examiner can normally be reached 7:00am-3:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton A. Brooks can be reached at 571-270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SEONG JONG KIM/ Examiner, Art Unit 1621
/CLINTON A BROOKS/ Supervisory Patent Examiner, Art Unit 1621
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