DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. 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 cited rejections 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.
3. Response to Election/Restriction filed on 7/27/2026 is acknowledged.
4. Claim filed on 7/27/2026 is acknowledged.
5. Claims 13-16 have been cancelled.
6. New claims 24-33 have been added.
7. Claims 1-12 and 17-33 are pending in this application.
8. Claims 1-12 and 17 are withdrawn from consideration pursuant to 37 CFR 1.142(b), as being drawn to non-elected inventions, there being no allowable generic or linking claim.
9. Claims 18-33 are under examination.
Election/Restrictions
10. Applicant’s election without traverse of Group 3 (claims 18-33) and election without traverse of compound with the structure
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as species of compound of formula (I) or formula (II) or tautomeric or stereochemically isomeric forms thereof; E.coli as species of bacterial infection; and the treatment of bacterial infections of Gram-negative bacteria as species of effect of the treatment in the reply filed on 7/27/2026 is acknowledged. The requirement is made FINAL in this office action.
Group 3 is drawn to a method of treating an individual suffering from bacterial infection, the method comprising administering to the individual an effective amount of a compound of formula (I) or formula (II):
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, including tautomeric or stereochemically isomeric forms thereof, or an N-oxide thereof or a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable solvate thereof, and wherein formula (I) excludes laterocidine, relacidine A and relacidine B or a pharmaceutical composition comprising such compound and a pharmaceutically acceptable carrier or diluent. A search was conducted on the elected species; and compound with the structure
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as the elected species of compound of formula (I) or formula (II) or tautomeric or stereochemically isomeric forms thereof appears to be free of prior art. However, prior art was found for E.coli as the elected species of bacterial infection; and the treatment of bacterial infections of Gram-negative bacteria as the elected species of effect of the treatment. A search was extended to the genus in claims 18 and 21; and prior art was found. Claims 18-33 are examined on the merits in this office action.
Objections
11. The abstract is objected to for the following minor informality: The instant abstract recites various chemical groups. However, 0 in some of these recited chemical groups should be O. As an example, -C(0)0Rz recited in the abstract should be -C(O)ORz. Applicant is required to correct these errors.
12. The specification is objected to for the following minor informality: The specification recites various chemical formulae/structures throughout the specification. However, the quality of these chemical formulae/structures are very poor. Applicant is required to amend the specification to provide clear image of the recited chemical formulae/structures.
Please note: The specification has not been checked to the extent necessary to determine the presence of all possible error. Applicant's cooperation is required in correcting any errors of which applicant may become aware in the specification (see MPEP § 608.01).
13. The drawings are objected to for the following minor informality:
There is no brief description of the drawings in instant specification.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
14. Claims 18 and 21 are objected to for the following minor informality: Applicant is suggested to amend these claims as “…a compound of formula (I) or (II):
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, or
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, wherein: R1 represents…each Rz independently represents…; or a tautomeric or stereochemically isomer thereof, an N-oxide thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof; and wherein the compound of formula (I) excludes…”.
15. Claims 20 and 23 are objected to for the following minor informality: Applicant is suggested to amend these claims as “…wherein the Gram-negative bacteria is selected from the group consisting of…and Pseudomonas aeruginosa (P. aeruginosa)”.
Furthermore, claim 20 contains various acronyms “E. coli”, “K. pneumoniae”, “A. baumannii” and “P. aeruginosa”. An acronym in the first instance of claims should be expanded upon/spelled out with the acronym indicated in parentheses, for example, Pseudomonas aeruginosa (P. aeruginosa). The abbreviations can be used thereafter.
Rejections
Claim Rejections - 35 U.S.C. § 112 paragraph (d)
16. 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 35 U.S.C. 112 (pre-AIA ), fourth paragraph:
Subject to the [fifth paragraph of 35 U.S.C. 112 (pre-AIA )], 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.
17. Claims 19 and 22 are rejected under 35 U.S.C. 112(d) or 35 U.S.C. 112 (pre-AIA ), 4th paragraph, 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. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
18. Claim 19 depends on claim 18; and claim 22 depends on claim 21. The method recited in either instant claim 19 or 22 includes both treating and preventing bacterial infection. However, the method recited in instant claim 18 or 21 is a method of treating bacterial infection. Therefore, the scope of the method recited in instant claim 19 or 22 is broader than the scope of the method recited in instant claim 18 or 21. Thus, claim 19 or 22 is improper dependent form for failing to further limit the subject matter of claim 18 or 21.
Claim Rejections - 35 U.S.C. § 112 paragraph (a)
Written Description
19. The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
20. Claims 18-33 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient” (MPEP § 2163).
A claimed genus may be satisfied through sufficient description of a representative number of species or disclosure of relevant, identifying characteristics such as functional characteristics coupled with a known or disclosed correlation between function and structure (MPEP § 2163(3)a(II)). The number of species that describe the genus must be adequate to describe the entire genus; if there is substantial variability, a large number of species must be described.
The analysis for adequate written description considers (a) actual reduction to practice, (b) disclosure of drawings or structural chemical formulas, (c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties or functional characteristics when coupled with known or disclosed correlation with structure, and (d) representative number of samples.
In the instant case, claims 18-33 are drawn to a method of treating an individual suffering from bacterial infection, the method comprising administering to the individual an effective amount of a compound of formula (I) or formula (II):
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, including tautomeric or stereochemically isomeric forms thereof, or an N-oxide thereof or a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable solvate thereof, and wherein formula (I) excludes laterocidine, relacidine A and relacidine B or a pharmaceutical composition comprising such compound and a pharmaceutically acceptable carrier or diluent.
The genus of instant claimed compound of formula (I) or formula (II) or a tautomeric or stereochemically isomer thereof, an N-oxide thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof is extremely broad, including a huge number of linear peptides having at least 13 residues or their N-acylated macrolactams, macrolactones or lanthipeptides (X=NH, O, S) having a side-chain to C-terminus pentapeptide.
The instant specification discloses the compound of formula (I) as analog of laterocidine and relacidine; and the compound of formula (II) as linear analog of laterocidine and relacidine, wherein laterocidine and relacidine are antibacterial compounds against Gram-negative bacteria.
The issue at question is whether a person of ordinary skilled in the art would be able to determine what structural feature/amino acid sequence is required for the instant claimed compound of formula (I) or formula (II) or a tautomeric or stereochemically isomer thereof, an N-oxide thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof to have the functional characteristics of being an antibacterial compound.
(a) actual reduction to practice and (b) disclosure of drawings or structural chemical formulas:
In the instant case, the instant specification discloses the compound of formula (I) as analog of laterocidine and relacidine; and the compound of formula (II) as linear analog of laterocidine and relacidine, wherein laterocidine and relacidine are antibacterial compounds against Gram-negative bacteria.
The instant specification further discloses the stability of these compounds can be improved where X is NH, as opposed to being O in the natural product.
The instant specification also discloses limited examples of the instant claimed compound of formula (I) or formula (II) or a tautomeric or stereochemically isomer thereof, an N-oxide thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof. And laterocidamide, ent-laterocidine, 8 lipid analogs of laterocidine, 14 position 9 analogs of linear laterocidine, 13 alanine-substituted linear analogs of laterocidine, Dap9-relacidamide A, and 12 analogs of relacidine (without structure presented) are tested in the working example in instant specification for antibacterial effect against very limited number of Gram-negative bacteria.
Taken all these together, other than the limited examples, the instant specification fails to describe a general correlation between structure and function for the instant claimed compound of formula (I) or formula (II) or a tautomeric or stereochemically isomer thereof, an N-oxide thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof to have the functional characteristics of being an antibacterial compound.
(c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties or functional characteristics when coupled with known or disclosed correlation with structure:
As discussed above, in the instant case, based on the disclosure of instant specification, other than the limited examples, a person of ordinary skilled in the art would not be able to determine a general correlation between structure and function for the instant claimed compound of formula (I) or formula (II) or a tautomeric or stereochemically isomer thereof, an N-oxide thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof to have the functional characteristics of being an antibacterial compound.
With regards to the instant claimed compound of formula (I) or formula (II) or a tautomeric or stereochemically isomer thereof, an N-oxide thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof to have the functional characteristics of being an antibacterial compound, Cochrane et al (PNAS, 2016, 113, pages 11561-11566, filed with IDS) teach the tridecaptin analogs TriA1 and Oct-TriA1 with the structures
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as antibacterial compound against Gram-negative bacteria, for example, Abstract; and page 11562, Figure 1. The tridecaptin analogs TriA1 and Oct-TriA1 in Cochrane et al meet the limitations of the compound of instant formula (II). Maloy et al (US 5470950 A) teach peptide acetyl-KLLKKLKKLLKLL-NH2 (a compound of instant formula (II)) as an antibacterial compound against Gram-negative bacteria, for example, column 4, lines 55-58; column 10, X-(SEQ ID NO: 3)-NH2 in Table I; and columns 11-14, SEQ ID NO: 3.
However, Jangra et al (Scientific Reports, 2019, 9, pages 1-10, filed with IDS), throughout the literature, teach various variants of tridecaptin, wherein a minor change in the amino acid sequence of tridecaptin results in different activity against the tested Gram-negative bacteria, for example, Abstract; page 4,Table 1; and page 5, Table 2.
Furthermore, it is well known in the peptide/protein art that even single amino acid changes or differences in the amino acid sequence of a protein/peptide can have dramatic effects on the protein/peptide’s function and/or properties. As an example of the unpredictable effects of mutations on protein/peptide’s function and/or properties, Drumm et al (Annu. Rev. Pathol. Mech. Dis., 2012, 7, pages 267-282) teach cystic fibrosis is an autosomal recessive disorder caused by mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene, for example, page 268, Section “CYSTIC FIBROSIS”. Drumm et al further teach several mutations can cause cystic fibrosis, including two mutations G551D and G551S; and clinical consequences are quite different for these two changes, as the G551D variant has virtually no detectable activity, and consequently a classic, severe phenotype is associated; G551S, however, has reduced but clearly detectable function and is associated with a much milder presentation of CF, for example page 269, left column, the last paragraph. Drumm et al also teach that in the most common cystic fibrosis mutation ΔF508 (the absence of amino acid 508 of the normally 1,480-amino acid protein) gives rise to the cystic fibrosis phenotype, for example, page 268, right column, the 2nd paragraph. Thus, even the substitution or deletion of a single amino acid can have dramatic and unpredictable effects on the function of the protein/peptide. The unpredictability of the effect of amino acid substitution on the function and/or property of peptide/protein is further confirmed and discussed in Yampolsky et al (Genetics, 2005, 170, pages 1459-1472). Yampolsky et al teach even conservative substitution can significantly affect the function of the protein/peptide, for example, page 1465, Table 3. Although the disclosures of Drumm et al and Yampolsky et al are directed to proteins/peptides other than antibacterial compound/peptide, they illustrate the inherent unpredictability with respect to the function and/or property of a given protein/peptide after even minor changes to the primary amino acid sequence.
Therefore, based on the state of art, a person of ordinary skilled in the art would not be able to determine a general correlation between structure and function for the instant claimed compound of formula (I) or formula (II) or a tautomeric or stereochemically isomer thereof, an N-oxide thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof to have the functional characteristics of being an antibacterial compound.
(d) representative number of samples:
In the instant case, the genus of instant claimed compound of formula (I) or formula (II) or a tautomeric or stereochemically isomer thereof, an N-oxide thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof is extremely broad, including a huge number of linear peptides having at least 13 residues or their N-acylated macrolactams, macrolactones or lanthipeptides (X=NH, O, S) having a side-chain to C-terminus pentapeptide.
And, as discussed in (a) and (b) above, the instant specification discloses the compound of formula (I) as analog of laterocidine and relacidine; and the compound of formula (II) as linear analog of laterocidine and relacidine, wherein laterocidine and relacidine are antibacterial compounds against Gram-negative bacteria.
The instant specification further discloses the stability of these compounds can be improved where X is NH, as opposed to being O in the natural product.
The instant specification also discloses limited examples of the instant claimed compound of formula (I) or formula (II) or a tautomeric or stereochemically isomer thereof, an N-oxide thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof. And laterocidamide, ent-laterocidine, 8 lipid analogs of laterocidine, 14 position 9 analogs of linear laterocidine, 13 alanine-substituted linear analogs of laterocidine, Dap9-relacidamide A, and 12 analogs of relacidine (without structure presented) are tested in the working example in instant specification for antibacterial effect against very limited number of Gram-negative bacteria.
Considering the broadness of the genus of instant claimed compound of formula (I) or formula (II) or a tautomeric or stereochemically isomer thereof, an N-oxide thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, the instant specification fails to provide sufficient examples to describe the entire genus of compound of formula (I) or formula (II) or a tautomeric or stereochemically isomer thereof, an N-oxide thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof to have the functional characteristics of being an antibacterial agent claimed.
Taken all these together, considering the state of the art and the disclosure in instant specification, it is deemed that the instant specification fails to provide adequate written description for the claimed genus of compound of formula (I) or formula (II) or a tautomeric or stereochemically isomer thereof, an N-oxide thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof to have the functional characteristics of being an antibacterial agent claimed; and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Claim Rejections - 35 U.S.C. § 112 paragraph (a)
Scope of Enablement
21. The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
22. Claims 18-33 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification while being enabling for a method of treating Gram-negative bacterial infection in an individual in need thereof with the compounds tested being active in the specification, the tridecaptin analogs TriA1 and Oct-TriA1 in Cochrane et al (PNAS, 2016, 113, pages 11561-11566, filed with IDS), and the peptide acetyl-KLLKKLKKLLKLL-NH2 in Maloy et al (US 5470950 A), does not reasonably provide enablement for a method of treating ALL bacterial infection or preventing ANY bacterial infection with a compound of formula (I) or formula (II) or a tautomeric or stereochemically isomer thereof, an N-oxide thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof. The specification does not enable any person skilled in the art to which it pertains to make and/or use the invention commensurate in scope with the claims.
The factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Among these factors are: (1) the nature or the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. When the above factors are weighed, it is the Examiner’s position that one skilled in the art could not practice the invention without undue experimentation.
(1) The nature of the invention and (5) The breadth of the claims:
The instant claims 18-33 are drawn to a method of treating an individual suffering from bacterial infection, the method comprising administering to the individual an effective amount of a compound of formula (I) or formula (II):
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, including tautomeric or stereochemically isomeric forms thereof, or an N-oxide thereof or a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable solvate thereof, and wherein formula (I) excludes laterocidine, relacidine A and relacidine B or a pharmaceutical composition comprising such compound and a pharmaceutically acceptable carrier or diluent.
Please note: The rejection to instant claimed compound of formula (I) or formula (II) or a tautomeric or stereochemically isomer thereof, an N-oxide thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof as an antibacterial agent under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph (written description) has been set forth in Section 20 above.
The genus of instant claimed compound of formula (I) or formula (II) or a tautomeric or stereochemically isomer thereof, an N-oxide thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof is extremely broad, including a huge number of linear peptides having at least 13 residues or their N-acylated macrolactams, macrolactones or lanthipeptides (X=NH, O, S) having a side-chain to C-terminus pentapeptide. In the instant case, the instant specification discloses the compound of formula (I) as analog of laterocidine and relacidine; and the compound of formula (II) as linear analog of laterocidine and relacidine, wherein laterocidine and relacidine are antibacterial compounds against Gram-negative bacteria.
With regards to bacteria, the Bacteria A-Z document (2026, pages 1-17, from https://app.gideononline.com/az/pathogens/bacteria) teaches there are 2122 different bacteria (see for example, page 1). Both the Infectious Diseases-Bacteria document (from https://libguides.mskcc.org/infectiousdiseases/Bacteria, 2026, pages 1-6) and the Classification of Common Pathogenic Bacteria document (2026, pages 1-4, from https://www.merckmanuals.com/professional/multimedia/table/classification-of-common-pathogenic-bacteria) teach there are different types of bacteria, such as Gram-positive bacteria, Gram-negative bacteria and so on.
With regards to “prevent” recited in instant claims 19 and 22, the instant specification fails to define it.
The term “prevent” implies perfect blocking from getting any bacterial infection.
(2) The state of the prior art and (4) The predictability or unpredictability of the art:
With regarding to treat ALL bacterial infection or prevent ANY bacterial infection with the instant claimed compound of formula (I) or formula (II) or a tautomeric or stereochemically isomer thereof, an N-oxide thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, the art is unpredictable.
Cochrane et al (PNAS, 2016, 113, pages 11561-11566, filed with IDS) teach the tridecaptin analogs TriA1 and Oct-TriA1 with the structures
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as antibacterial compound against Gram-negative bacteria, for example, Abstract; and page 11562, Figure 1. The tridecaptin analogs TriA1 and Oct-TriA1 in Cochrane et al meet the limitations of the compound of instant formula (II). Maloy et al (US 5470950 A) teach peptide acetyl-KLLKKLKKLLKLL-NH2 (a compound of instant formula (II)) as an antibacterial compound against Gram-negative bacteria, for example, column 4, lines 55-58; column 10, X-(SEQ ID NO: 3)-NH2 in Table I; and columns 11-14, SEQ ID NO: 3. However, none of these references teaches treating Gram-positive bacterial infection with such compounds.
Furthermore, the Bacterial Infection document (2026, pages 1-6, from https://my.clevelandclinic.org/health/diseases/24189-bacterial-infection) teaches various routes to get a bacterial infections; and ways to reduce the risk of various types of bacterial infections, for example, pages 2-3, Section “Bacterial infection causes”; and page 5, Section “Prevention”. However, it does not teach how to completely block from getting any bacterial infection.
Taken all these together, considering the state of art, one of ordinary skilled in the art would understand and reasonably expect that it would not be able to treat ALL bacterial infection or prevent ANY bacterial infection with the instant claimed compound of formula (I) or formula (II) or a tautomeric or stereochemically isomer thereof, an N-oxide thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof.
(3) The relative skill of those in the art:
The related skill of those in the art is high.
(6) The amount of direction or guidance presented and (7) The presence or absence of working examples:
With regarding to using the instant claimed compound of formula (I) or formula (II) or a tautomeric or stereochemically isomer thereof, an N-oxide thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof for treating and/or preventing bacterial infection in an individual in need thereof, the instant specification discloses the compound of formula (I) as analog of laterocidine and relacidine; and the compound of formula (II) as linear analog of laterocidine and relacidine, wherein laterocidine and relacidine are antibacterial compounds against Gram-negative bacteria.
The instant specification further discloses the stability of these compounds can be improved where X is NH, as opposed to being O in the natural product.
The instant specification also discloses limited examples of the instant claimed compound of formula (I) or formula (II) or a tautomeric or stereochemically isomer thereof, an N-oxide thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof. And laterocidamide, ent-laterocidine, 8 lipid analogs of laterocidine, 14 position 9 analogs of linear laterocidine, 13 alanine-substituted linear analogs of laterocidine, Dap9-relacidamide A, and 12 analogs of relacidine (without structure presented) are tested in the working example in instant specification for antibacterial effect against very limited number of Gram-negative bacteria.
Furthermore, the instant specification fails to provide any guidance on how to prevent bacterial infection. There is no clear guidance as to how to determine the patient population. The bacterial infection can be treated once it is diagnosed; however, it cannot be prevented since the patient population is unknown.
Taken all these together, the instant specification does not enable any person skilled in the art to which it pertains to make and/or use the invention commensurate in scope with the claims. There is a lack of adequate guidance from the specification or prior art with regard to the actual method of using the instant claimed compound of formula (I) or formula (II) or a tautomeric or stereochemically isomer thereof, an N-oxide thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof for treating ALL type of bacterial infection and/or prevent ANY types of bacterial infection. Applicant's limited disclosure is noted but is not sufficient to justify claiming a method of using the instant claimed compound of formula (I) or formula (II) or a tautomeric or stereochemically isomer thereof, an N-oxide thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof as an antibacterial agent for treating ALL type of bacterial infection and/or prevent ANY types of bacterial infection.
(8) The quantity of experimentation necessary:
Considering the state of prior arts and the disclosure in instant specification, one of ordinary skill in the art would be burdened with undue experimentation to use the instant claimed compound of formula (I) or formula (II) or a tautomeric or stereochemically isomer thereof, an N-oxide thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof as an antibacterial agent for treating ALL type of bacterial infection and/or prevent ANY types of bacterial infection.
Claim Rejections - 35 U.S.C. § 102(a)(1)
23. 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.
24. Claims 18-25 and 29-32 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cochrane et al (PNAS, 2016, 113, pages 11561-11566, filed with IDS).
The instant claims 18-25 and 29-32 are drawn to a method of treating an individual suffering from bacterial infection, the method comprising administering to the individual an effective amount of a compound of formula (I) or formula (II):
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, including tautomeric or stereochemically isomeric forms thereof, or an N-oxide thereof or a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable solvate thereof, and wherein formula (I) excludes laterocidine, relacidine A and relacidine B or a pharmaceutical composition comprising such compound and a pharmaceutically acceptable carrier or diluent.
Cochrane et al, throughout the literature, teach the tridecaptin analogs TriA1 and Oct-TriA1 with the structures
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as antibacterial compound against Gram-negative bacteria, such as E. coli; and a pharmaceutical composition comprising TriA1 or Oct-TriA1 and a pharmaceutically acceptable carrier or diluent is effectively against E. coli infection in vitro, for example, Abstract; page 11562, Figures 1 and 2; page 11563, Figure 4; page 11565, Figure 8; and Section “Materials and Methods”. The tridecaptin analogs TriA1 and Oct-TriA1 in Cochrane et al meet the limitations of the compound of instant formula (II) recited in instant claims 18, 21, 24, 25 and 29-32 in that R1 is either
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144
media_image6.png
Greyscale
or
PNG
media_image7.png
96
146
media_image7.png
Greyscale
, R2a is
PNG
media_image8.png
40
50
media_image8.png
Greyscale
, R2b is
PNG
media_image9.png
76
40
media_image9.png
Greyscale
, R2c is H, R2d is
PNG
media_image10.png
40
42
media_image10.png
Greyscale
, R2e is
PNG
media_image11.png
108
92
media_image11.png
Greyscale
, R2f is
PNG
media_image12.png
52
78
media_image12.png
Greyscale
, R2g is
PNG
media_image13.png
54
132
media_image13.png
Greyscale
, R2h is
PNG
media_image14.png
58
122
media_image14.png
Greyscale
, R3 is
PNG
media_image15.png
132
98
media_image15.png
Greyscale
, R2i is
PNG
media_image16.png
116
124
media_image16.png
Greyscale
, R2j is
PNG
media_image8.png
40
50
media_image8.png
Greyscale
, R2k is
PNG
media_image17.png
86
78
media_image17.png
Greyscale
, R2l is
PNG
media_image18.png
66
50
media_image18.png
Greyscale
, X is O and Rz is H. And in the instant case, in view of the teachings of Cochrane et al as a whole, one of ordinary skilled in the art would at once envision a method of treating Gram-negative bacterial infection, such as E. coli infection, in an individual in need thereof, wherein the method comprises administering to the individual a therapeutically effective amount of TriA1 or Oct-TriA1 or a pharmaceutical composition comprising a therapeutically effective amount of such compound and a pharmaceutically acceptable carrier or diluent. It reads on E.coli as the elected species of bacterial infection; and the treatment of bacterial infections of Gram-negative bacteria as the elected species of effect of the treatment. And it meets the limitations of instant claims 18-25 and 29-32.
Since the reference teaches all the limitations of instant claims 18-25 and 29-32; the reference anticipates instant claims 18-25 and 29-32.
25. Claims 18-23, 26-28, 32 and 33 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Maloy et al (US 5470950 A).
The instant claims 18-23, 26-28, 32 and 33 are drawn to a method of treating an individual suffering from bacterial infection, the method comprising administering to the individual an effective amount of a compound of formula (I) or formula (II):
PNG
media_image2.png
520
718
media_image2.png
Greyscale
, including tautomeric or stereochemically isomeric forms thereof, or an N-oxide thereof or a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable solvate thereof, and wherein formula (I) excludes laterocidine, relacidine A and relacidine B or a pharmaceutical composition comprising such compound and a pharmaceutically acceptable carrier or diluent.
Maloy et al, throughout the patent, teach biologically active amphiphilic peptides as antibacterial agent; and a method of treating bacterial infection in an individual in need thereof, wherein the method comprises administering to the individual a pharmaceutical composition comprising a therapeutically effect amount of such peptide and a pharmaceutically acceptable carrier, and wherein the bacteria can be Gram-negative bacteria, such as E. coli, for example, Abstract; column 5, line 65 to column 6, line 1; column 6, lines 11-15 and 45-48; and column 10, Table I. One of such peptides in Maloy et al is acetyl-KLLKKLKKLLKLL-NH2, for example, column 4, lines 55-58; column 10, X-(SEQ ID NO: 3)-NH2 in Table I; and columns 11-14, SEQ ID NO: 3. The peptide acetyl-KLLKKLKKLLKLL-NH2 in in Maloy et al has the structure
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424
946
media_image19.png
Greyscale
, which meets the limitations of the compound of instant formula (II) recited in instant claims 18, 21, 26-28, 32 and 33 in that R1 is an acetyl group, R2a is
PNG
media_image20.png
86
122
media_image20.png
Greyscale
, R2b is
PNG
media_image21.png
76
72
media_image21.png
Greyscale
, R2c is
PNG
media_image21.png
76
72
media_image21.png
Greyscale
, R2d is
PNG
media_image20.png
86
122
media_image20.png
Greyscale
, R2e is
PNG
media_image20.png
86
122
media_image20.png
Greyscale
, R2f is
PNG
media_image21.png
76
72
media_image21.png
Greyscale
, R2g is
PNG
media_image20.png
86
122
media_image20.png
Greyscale
, R2h is
PNG
media_image20.png
86
122
media_image20.png
Greyscale
, R3 is
PNG
media_image21.png
76
72
media_image21.png
Greyscale
, R2i is
PNG
media_image21.png
76
72
media_image21.png
Greyscale
, R2j is
PNG
media_image20.png
86
122
media_image20.png
Greyscale
, R2k is
PNG
media_image21.png
76
72
media_image21.png
Greyscale
, R2l is
PNG
media_image21.png
76
72
media_image21.png
Greyscale
, X is NH and Rz is H. And in the instant case, in view of the teachings of Maloy et al as a whole, one of ordinary skilled in the art would at once envision a method of treating Gram-negative bacterial infection, such as E. coli infection, in an individual in need thereof, wherein the method comprises administering to the individual a therapeutically effective amount of peptide acetyl-KLLKKLKKLLKLL-NH2 or a pharmaceutical composition comprising a therapeutically effective amount of such peptide and a pharmaceutically acceptable carrier. It reads on E.coli as the elected species of bacterial infection; and the treatment of bacterial infections of Gram-negative bacteria as the elected species of effect of the treatment. And it meets the limitations of instant claims 18-23, 26-28, 32 and 33.
Furthermore, the MPEP states the following: A genus does not always anticipate a claim to a species within the genus. However, when the species is clearly named, the species claim is anticipated no matter how many other species are additionally named. See Ex parte A, 17 USPQ2d 1716 (Bd. Pat. App. & Inter. 1990) (see MPEP § 2131.02).
Since the reference teaches all the limitations of instant claims 18-23, 26-28, 32 and 33; the reference anticipates instant claims 18-23, 26-28, 32 and 33.
Conclusion
No claim is allowed.
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/LI N KOMATSU/Primary Examiner, Art Unit 1658
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