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
Pursuant to a preliminary amendment filed November 25, 2025, claims 1-14 are currently pending in the instant application.
Response to Election/Restriction
Applicant's election with traverse of Group I, claims 1-9, directed to a method of screening an inhibitor; and Applicant’s election of Species as follows:
Species (A): selecting a substance is performed by using one or more x-ray crystallography, cryogenic electron microscopy and NMR spectroscopy (claim 3); and
Species (B): an in vivo antibiotic resistance assay, or a minimal inhibitory concentration (MIC assay) measurement (claim 9), in the reply filed November 25, 2025 is acknowledged.
Response to Traversals:
The traversal of is on the grounds that: (a) Group I and Group III are closely related, therefore, there is no undue burden in examining both Group I and Group III claims (Applicant Remarks, pg. 5, fifth full paragraph)
Regarding (a), as indicated in the Requirement for Restriction-Election mailed 10-01-2025, the claims are directed to three (3) distinct inventions, wherein the process and/or products recited in the instant claims have been shown to be distinct or unrelated. As an initial matter, Applicant has elected Group I, process claims 1-9. Group III is directed to an antibacterial composition comprising the inhibitor of Group II and an MLSB antibiotic, such that the invention of Group III does not read on the process claims recited in Group I (e.g., a method for screening for an inhibitor that induces resistance to MLSB antibiotics). The invention of Group III is not related to the invention of Group I. Searching and/or examining the unrelated limitations including their mutually exclusive characteristics, places a serious examination and search burden on the Examiner. Thus, the requirement for election/restrictions is maintained.
Claims 10-14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on October 22, 2025.
Claims 2 and 4 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species, there being no allowable generic or linking claim.
Therefore, claims 1, 3 and 5-9 are under consideration to which the following grounds of rejection are applicable.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on October 19, 2012 is not in compliance with the provisions of 37 C.F.R. § 1.98(a)(2), which requires a legible copy of each U.S. and foreign patent; each publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed.
The following reference has not been considered by the examiner, as indicated on Form PTO 1449.
Foreign Reference 1: KR 1020010090992, of IDS filed on July 15, 2022 has not been considered because and English translation of the document has not been provided.
All other documents in said Information Disclosure Statement were considered as noted by the Examiner initials in the copy attached hereto.
Priority
The present application filed July 15, 2022, claims the benefit of Republic of Korea Application KR10-2021-0093127, filed July 15, 2021.
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in the Republic of Korea on July 15, 2021. It is noted, however, that applicant has not filed a certified copy of the Republic of Korea Patent Application No. KR10-2021-0093127 application as required by 37 CFR 1.55.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Claim Objections/Rejections
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(B) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 3 and 5-9 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 applicant regards as the invention.
Claim 1 is indefinite for the recitation of the term “a shortest motif X adjacent thereto, S-Q-N-F” such as recited in claim 1, line 4 because it is unclear whether “S-Q-N-F” is the shortest motif X adjacent to the NTER; whether the term indicates that there is a shortest motif X that is adjacent to the motif “S-Q-N-F” (where S-Q-N-F is not the shortest motif X); or whether the term refers to something else and, thus, the metes and bounds of the claim cannot be determined.
Claims 1 and 7 are indefinite for the recitation of the terms “X” and “S-Q-N-F” such as recited in claim 1, line 4 because X, S, Q, N and/or F are not defined in the claim, such that it is unclear whether each of the letters (or the combination of two or more letters) corresponds to one or more amino acids (e.g., serine, asparagine, etc.), to a specific atom or functional group (e.g., sulfur, nitrogen, etc.); or whether the terms refer to something else and, thus, the metes and bounds of the claim cannot be determined.
Claim 1 is indefinite for the recitation of the term “the shortest motif X adjacent thereto” such as recited in claim 1, lines 7-8. There is insufficient antecedent basis for the term “the shortest motif X adjacent thereto” in the claim because claim 1, line 4 recites the term “a shortest motif X adjacent thereto, S-Q-N-F.”
Claim 1 is indefinite for the recitation of the term “the substrate” such as recited in claim 1, line 8. There is insufficient antecedent basis in the claim for the term “the substrate” in the claim because claim 1, line 6 recites the term “an RNA substrate.”
Claim 1 is indefinite for the recitation of the term “the ligand in the Erm protein” such as recited in claim 1, line 8. There is insufficient antecedent basis for the term “the ligand in the Erm protein” in the claim because claim 1, line 6 recites the term “a ligand,” where no ligand is recited to be in the Erm protein.
Claim 1 is indefinite for the recitation of the term “the motif X” such as recited in claim 1, line 9. There is insufficient antecedent basis for the term “the motif X” in the claim because claim 1, line 4 recites the term “a shortest motif X adjacent thereto, S-Q-N-F.”
Claims 1 and 9 are indefinite for the recitation of the term “the methylation activity” such as recited in claim 1, line 10. There is insufficient antecedent basis for the term “the methylation activity” in the claim.
Claim 6 is indefinite for the recitation of the term “a distance” such as recited in claim 6, line 2 because claim 6 depends from instant claim 1, wherein claim 1 does not recite that there is a distance between the Erm protein and the RNA substrate and/or ligand. Moreover, it is unclear whether the “conformational change” is indicated by the presence of any distance between the Erm protein and the RNA substrate and/or ligand; or whether it is based on a change in the distance between the Erm protein and the RNA substrate and/or ligand and, thus, the metes and bounds of the claim cannot be determined.
Claim 7 is indefinite for the recitation of the term “the shortest motif X, S-Q-N-F” such as recited in claim 7, line 2. There is insufficient antecedent basis for the term “the shortest motif X, S-Q-N-F” in the claim because claim 1, line 4 recites the term “a shortest motif X adjacent thereto, S-Q-N-F.”
Claim 7 is indefinite for the recitation of the terms “the nitrogen;” “the carbamoyl group;” “the phenyl group;” “the side chain hydroxyl group;” “the 6th nitrogen;” and “the adenine” such as recited in claim 7, lines 2-6. There is insufficient antecedent basis for the terms in the claim. Moreover, claim 7 depends from claims 1 and 6, wherein claims 1 and 6 do not recite the presence of a nitrogen, a carbamoyl group, a phenyl group, a side chain hydroxyl group, a 6th nitrogen, and/or an adenine and, thus, the metes and bounds of the claim cannot be determined.
Claim 7 is indefinite for the recitation of the term “a methylation target” such as recited in claim 7, line 6 because claim 7 depends from claim 1 and 6, wherein claims 1 and 6 do not recite a methylation target, and it is unclear if any of the preceding terms is a “methylation target” and, thus, the metes and bounds of the claim cannot be determined.
Claim 9 is indefinite for the recitation of the term “the candidate substance identified to lead to inhibition or elimination of the methylation activity” such as recited in claim 9, lines 1-2 because claim 9 depends from claim 1, wherein claim 1 does not recite that a candidate substance “is identified to lead to inhibition or elimination of the methylation activity.” Instant claim 1 recites ‘selecting a candidate substance’ and, thus, the metes and bounds of the claim cannot be determined.
Claims 3, 5 and 8 are indefinite insofar as they ultimately depend from instant claim 1.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 6, 7 and 9 are rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 6 recites (in part): “wherein the conformational change is change in a length of the NTER of the Erm protein or a distance between the Erm protein and the RNA substrate and/or ligand” in lines 1-3 because claim 6 depends from instant claim 1, wherein claim 1 does not recite that there is a distance between the Erm protein and the RNA substrate and/or ligand. Thus, claim 6 is an improper dependent claim for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 7 recites (in part): “wherein the candidate substance causes a conformational change in the shortest motif X, S-Q-N-F by changing the distance between the nitrogen of the carbamoyl group in Q and an oxygen of a hydroxyl group in S…in the adenine, a methylation target” in lines 1-6 because claim 7 depends from instant claims 1 and 6, wherein claims 1 and 6 do not recite the presence of a nitrogen, a carbamoyl group, a phenyl group, a side chain hydroxyl group, a sixth nitrogen, an adenine and/or a methylation target. Thus, claim 7 is an improper dependent claim for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 9 recites (in part): “further comprising applying the candidate substance identified to lead to inhibition or elimination of the methylation activity” in lines 1-2 because claim 9 depends from claim 1, wherein claim 1 recites “to select a candidate substance,” such that no candidate substance is recited to be “identified to lead to inhibition or elimination of the methylation activity”. Thus, claim 9 is an improper dependent claim for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
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 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.
Claims 1, 3 and 5-9 are rejected under 35 U.S.C. 102(a1)/102(a2) as being anticipated by Lee et al. (hereinafter “Lee”) (Antibiotics, 2021, 10(264), 1-17).
Regarding claim 1, Lee teaches that it has long been considered that because MLSB antibiotics have quite different chemical structures but share a common resistance mechanism, the exocyclic N6-methylation of a specific adenine residue (A2058 in 23S rRNA, Escherichia coli coordinate), they are categorized into one superfamily of antibiotics, such that this target site modification is carried out by a family of enzymes named erythromycin ribosome methylation (Erm); and it has long been considered that the specific inhibitors to the members of the Erm family could help overcome antibiotic resistance to attain the proper therapeutic goals, wherein the development of inhibitors includes screening and detecting compounds possessing a potential inhibitory activity using nuclear magnetic resonance (NMR)-based screening and chemical synthesis based on that, could lead to novel compounds that bind to the S-adenosyl-L-methionine (SAM) binding sites of ErmC’ and ErmB, which demonstrated that the resistance could be overcome using them; as well as, the virtual screening of compounds based on the structure of Erm protein and their characterization by in vitro potency, and proposals to design the inhibitors based on the minimal substrate features have been reported (interpreted as designing a substance; overcoming resistance; screening for inducers or inhibitors of MLSB; binds an RNA substrate; induces a conformational change; selecting a compound; using NMR; ErmC’; and substate is 23S rRNA, claims 1, 3, 5 and 8) (pg. 1, first partial paragraph, lines 8-13; and pg. 2, first partial paragraph, lines 1-10). Lee teaches that alignment of the NTER and the shortest motif X of erythromycin ribosome methylation (Erm) proteins indicates that the NTER encompasses the N-terminal end up to the shortest motif X is represented by GQNF, wherein the shortest motif X in ErmC proteins are represented by SQNF; and there is a wide range of variation in the length of the NTER among Erm proteins (interpreted as Erm proteins; and conformation change in a region of NTER and/or the shortest motif X; and SQNF, claim 1) (pg. 4. Figure 1, lines 1-4).
Regarding claims 3 and 5, Lee teaches that it has long been considered that the specific inhibitors to the members of the Erm family could help overcome antibiotic resistance to attain the proper therapeutic goals, wherein the development of inhibitors includes screening and detecting compounds possessing a potential inhibitory activity using nuclear magnetic resonance (NMR)-based screening and chemical synthesis based on that, could lead to novel compounds that bind to the S-adenosyl-L-methionine (SAM) binding sites of ErmC’ and ErmB, which demonstrated that the resistance could be overcome using them (interpreted as selecting a compound using NMR, claims 3 and 5) (pg. 2, first partial paragraph, lines 3-7).
Regarding claim 6, Lee teaches that this conformational change of protein could be accompanied with that of RNA substrate because the previous complex structure based on the amino acid mutagenesis study and restriction of protein conformation could not predict the interaction between SQNF in ErmC’ and RNA and their distance was too far to make contact, where there is much variation in length and identities of amino acids constituting this region (NTER), such that this region or part of it could contribute to the shifting of substrate specificity from that of KsgA to Erm’s, such that the Erm protein might assume a distinct local structure with bound substrate RNA in this region and provide the target site to develop the unique inhibitors for enhanced selectivity and with high potency (interpreted as changing the length of the NTER or a distance between the Erm protein and the RNA substrate, claim 6) (pg. 12, last partial paragraph through pg. 13, first partial paragraph).
Regarding claims 7 and 8, Lee teaches that Figure 7 illustrates conformational change of S–Q–F residues in ErmC’ structures with binding to different cofactors: (a) after being docked by the target adenine, the distance between nitrogen of the carbamoyl group of Q10 and oxygen of the hydroxyl group of S9 is shortened as seen in (c) and (d) in Figure 6, and in (c) in this Figure 7, wherein conformations of S–Q–F with the SAM-bound structure are modestly different from those of SAH, with S9 being quite distinct (interpreted as conformation change; and distance between the nitrogen of the carbamoyl group in Q and oxygen of a hydroxyl group in S; and ErmC’, claims 7 and 8) (pg. 11, Figure 7, lines 1-2 and 7-10). Lee teaches that materials include His6-tagged Erm proteins and the sequence domain V of 23S rRNA (interpreted as 23S rRNA, domain V substrate, claim 8) (pg. 13, Section 4.1, first full paragraph, lines 1-3).
Regarding claim 9, Lee teaches an in vivo antibiotic susceptibility assay for ErmS and its mutant proteins (interpreted as applying the candidate substance to an antibiotic resistance assay, claim 9) (pg. 14, first full paragraph)
Lee meets all the limitations of the claims and, therefore, anticipates the claimed invention.
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 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 may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived 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 1, 3 and 5-9 are rejected under 35 U.S.C. 103 as being unpatentable over Maravic et al. (hereinafter “Maravic”) (Nucleic Acids Research, 2003, 31(16), 4941-4949) in view of Foik et. al. (hereinafter “Foik”) (European Journal of Medicinal Chemistry, 2018, 146, 60-67) as evidenced by Lee et al. (hereinafter “Lee”) (Antibiotics, 2021, 10(264), 1-17).
Regarding claim 1, Maravic teaches that the Erm family of adenine-N6 methyl-transferases (MTases) is responsible for the development of resistance to macrolide-lincosamide-streptogramin B antibiotics through the methylation of 23S ribosomal RNA; and based on the mutagenesis data, a preliminary three-dimensional model of ErmC’ complexed with the minimal substrate was constructed, such that the identification of the RNA-binding site of ErmC’ can be useful for structure-based design of novel drugs that do not necessarily bind to the cofactor binding site common to many S-adenosyl-L-methionine-dependent MTases, but specifically block the substrate-binding site of MTases from the Erm family (interpreted as ErmC’; antibiotic resistance; substrate is 23S RNA; and designing a substance to inhibit resistance, claims 1 and 8) (Abstract, lines 1-5 and 23-32), wherein the shortest motif X at the NTER of ErmC comprises SQNF as evidenced by Lee (pg. 4, Figure 1). Maravic teaches that the compounds, which inhibit Erm MTases can sensitize MLS-resistant bacteria to macrolide antibiotics, as demonstrated both in vivo and in vitro for ErmC’ inhibitors, wherein Erm inhibitors used in combination with a broad-spectrum macrolide antibiotic could be potentially useful for the treatment of infections caused by MLS resistant pathogens, such that using the NMR-based screen and parallel synthesis, new lead compounds have been generated that: (i) bind to the AdoMet-binding site on the ErmAM and ErmC’ MTases and can reverse Erm-mediated MLS antibiotic resistance; and/or (ii) combating drug resistance by inhibiting the A2058 methylation by developing drugs that block the unique RNA-binding site of the Erm MTases (interpreted as screening compounds including drugs; inducing a conformational change; selecting a compound; and selecting using NMR, claims 1, 3 and 5) (pg. 2, col 1, second full paragraph). Maravic teaches that four side chains of the cleft, localized in the N-terminal domain, are essential for the MTase activity (interpreted as inherent modification of NTER, claims 1, 6 and 7) (pg. 8, col 2, first full paragraph, lines 3-5).
Regarding claims 3 and 5, Maravic teaches that the compounds, which inhibit Erm MTases can sensitize MLS-resistant bacteria to macrolide antibiotics, as demonstrated both in vivo and in vitro for ErmC’ inhibitors, wherein Erm inhibitors used in combination with a broad-spectrum macrolide antibiotic could be potentially useful for the treatment of infections caused by MLS resistant pathogens, such that using the NMR-based screen and parallel synthesis, new lead compounds have been generated (interpreted as selecting compound using NMR, claims 3 and 5) (pg. 2, col 1; second full paragraph, lines 1-10).
Regarding claims 6 and 7, Maravic teaches that four side chains of the cleft, localized in the N-terminal domain, are essential for the MTase activity; and that visual analysis of the ErmAM and ErmC’ structures reveals that the RNA-binding region of the N-terminal domain is stabilized by hydrophobic interactions with the C-terminal domain (interpreted as inherently changing the conformation in a length of NTER of the Erm protein; or a distance between the Erm protein and the RNA substrate, claims 1, 6 and 7) (pg. 8, col 2, first full paragraph, lines 3-5).
Regarding claim 8, Maravic teaches modeling of ErmC’-RNA interactions by modelling the substrate RNA including residues 2073-2090 and 2638-2651 of B. subtilis 23S rRNA (interpreted as a substrate comprising 23S rRNA, domain V or a fragment thereof (pg. 4, col 2, last partial paragraph).
Regarding claim 9, Maravic teaches a determination of erythromycin minimal inhibitory concentrations (MICs) (interpreted as applying the candidate substance to an MIC measurement, claim 9) (pg. 2, col 2, last full paragraph).
Maravic does not specifically exemplify that the conformational change is a change in length of the NTER, the distance between the Erm protein, the RNA substrate, and/or the distance between different chemical bonds (claims 6 and 7, both in part).
Regarding claims 6 (in part) and 7 (in part), Foik teaches a molecular docking approach followed by biochemical screening was applied to search for inhibitors targeting both cofactor and substrate binding pockets of ErmC’ methyltransferase, such that based on the results of the molecular docking-based virtual screening of the clean-leads subset of the ZINC database, 29 compounds were chosen for experimental verification including inhibitor 28 (ZINC code 32747906), with an IC50 of 100 mM, decreased the minimal inhibitory concentration of erythromycin in the Escherichia coli strain overexpressing ErmC' (interpreted as assaying for MIC), wherein docking analysis of inhibitor 28 to the ErmC’ structure and the competitive ligand binding assay revealed a non-competitive model of inhibition, such that inhibitor 28 served as a template for similarity-based virtual screening, which resulted in the identification of two derivatives 3s (ZINC code 62022572) and 4s (ZINC code 49032257) with an IC50 of 116 mM and 110 mM, respectively (interpreted as contacting a substance with an Erm protein and an RNA substrate; and candidate compounds that inherently cause a conformational change in the NTER or in the shortest motif X, SQNF including length or distance between atoms or RNA substrate, claims 1, 6 and 7) (Abstract). Foik teaches that potential lead compounds should selectively bind to the ErmC' to block its rRNA methylation activity, wherein the potency of the chosen compounds in the inhibition of ErmC' was determined at a concentration range of 125-500 mM, such that 23 compounds inhibited the in vitro activity of ErmC' (Table 1) (pg. 62, col 2, second full paragraph). Foik teaches that the biological effect of all the compounds was assessed by determining the erythromycin Minimum Inhibitory Concentration (MIC) values with the addition of the compound to E. coli DH5a cells expressing recombinant ErmC', where the compound's inhibitory activity in vivo is measured by its ability to prevent bacterial growth in the presence of erythromycin (interpreted as MIC and inhibition of methylation activity to an antibiotic resistance assay, claim 9) (pg. 62, col 2, last partial paragraph). Foik teaches that based on ligand docking into the target site, the probable chemical bonds between the inhibitors 28, 3s and 4s and the amino acid residues of ErmC’ were determined (Figure S1), wherein all three inhibitors interact with the same nine amino acids, e.g., Gln10, Asn 11, Phe12, Gly38, Gly40, Asn101, Ile102, Pro103, Tyr104; and the last four amino acids are included in the 100-GNIPY sequence found in motif IV (interpreted as an inherent distance between the Erm protein and the RNA substrate; and inherently causing a conformational change in the NTER, including in the shortest motif X, SQNF; and changing distances or lengths, claims 6 and 7) (pg. 65, col 1, last partial paragraph). Foik teach that both compound 3s and compound 4s improve the binding affinity of ErmC’ to rRNA, wherein a decrease of the ErmC’ affinity to rRNA might be the result of conformational changes in the RNA binding site; and compound 28 suggests that extending the compounds into the methionine part of the cofactor-binding pocket can increase the inhibitor's potency without the loss of its selectivity, such that in comparison to inhibitor 28, other previously reported noncompetitive inhibitors of ErmC’-BTB05276, RF00667 and PD00556 interact exclusively with the target adenine-binding pocket, where such binding can cause conformational changes in the protein structure, especially in the rRNA-binding site, and thus decrease the ErmC' affinity to RNA (KD = 8.26 ± 1.41 for BTB05276) (interpreted as a distance between the Erm protein and the RNA substrate; and encompassing a conformational change in the shortest motif X, SQNF including changes in atom/bond distances, claims 6 and 7) (pg. 65, col 2, first full paragraph). The Examiner notes that MPEP 2112.01(II) states that "products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.
“It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Moreover, it is prima facie obvious to combine prior art elements according to known methods to yield predictable results; the court held that, "…a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1395 (2007); Sakraida v. AG Pro, Inc., 425 U.S. 273, 282, 189 USPQ 449, 453 (1976); Anderson’s-Black Rock, Inc. v. Pavement Salvage Co., 396 U.S. 57, 62-63, 163 USPQ 673, 675 (1969); Great Atlantic & P. Tea Co. v. Supermarket Equipment Corp., 340 U.S. 147, 152, 87 USPQ 303, 306 (1950)”. Therefore, in view of the benefits of using a molecular docking approach followed by biochemical screening as exemplified by Foik, 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 modify the method of using an NMR-based screen and parallel synthesis for developing new lead compounds that bind ErmC’ MTases as disclosed by Maravic, to include virtual screening approaches including docking analyses followed by biochemical screening and selection as taught by Foik with a reasonable expectation of success in identifying and characterizing small molecule inhibitors of rRNA ErmC’ methyltransferase that can serve as adjuvants of macrolides; in selecting novel compounds that inhibit rRNA ErmC’ methyltransferase, block methyltransferase catalytic activity, and/or block resistance to macrolides, licosamides, and streptogramin B antibiotics; and/or in improving molecular docking models of ErmC’-RNA complex interactions including improvements in modeling ligand binding sites of ErmC’ to overcome bacterial resistance mechanisms.
Thus, in view of the foregoing, the claimed invention, as a whole, would have been obvious to one of ordinary skill in the art at the time the invention was made. Therefore, the claims are properly
rejected under 35 USC §103(a) as obvious over the art.
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 1, 3 and 5-9 are rejected on the ground of nonstatutory double patenting as being unpatentable over:
Claims 1-8 of U.S. Patent No. 12,037,642– a method for screening an antibiotic resistance expression inhibitor, comprising the steps of: contacting a double-stranded RNA molecule or a variant thereof with an Erm protein and a candidate substance, wherein the double-stranded RNA molecule or variant thereof is a substrate for methylation by the Erm protein, and the antibiotic is a macrolide-lincosamide-streptogramin B (MLSB) class antibiotic; and identifying whether the candidate substance inhibits the methylation by the Erm protein, wherein if the candidate substance inhibits the methylation, the candidate substance is selected as an antibiotic resistance expression inhibitor which inhibits expression of antibiotic resistance by inhibiting methylation by the Erm protein, thereby rendering microorganism expressing Erm protein sensitive to antibiotics, wherein the double-stranded RNA molecule or variant thereof is a double-stranded RNA molecule wherein the variant comprises one of the following mutations in the double-stranded RNA molecule, etc. (claim 1).
Although the claims at issue are not identical, they are not patentably distinct from each other because: the instant claims, and the claims of U.S. Patent No. 12037642 teach a method for screening an inhibitor of antibiotic resistance comprising contacting a substance with an Erm protein or complex of an Erm protein and an RNA substrate and/or ligand to select a candidate substance that induced and conformational change in a region containing the NTER and/or a site that binds to the substrate or the ligand in the Erm protein or the complex; and identifying whether the conformational change leads to inhibition or elimination of the methylation activity of the Erm protein.
Conclusion
Claims 1, 3 and 5-9 are rejected.
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/AMY M BUNKER/Primary Examiner, Art Unit 1684