DETAILED ACTION
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 .
Application Status
2. Applicants’ amendment and response, submitted March 3, 2026, has been reviewed by the examiner and entered of record in the file. Claim 1 is amended. Claim 13 is canceled. Claims 36 and 37 are newly added.
3. Claims 18-34, drawn to Groups II and III, were previously withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
4. Claims 1, 17, 36 and 37 are under examination and are the subject of this office action.
Specification
5. Applicant’s submission of the replacement abstract, filed March 3, 2026, is sufficient to overcome the previous objection of the abstract.
Response to Amendment
6. The Declaration under 37 CFR 1.132 filed March 3, 2026 by Muneo Shoji, is insufficient to overcome the rejection of claims 1, 13 and 17 based upon obviousness-type double patenting as set forth in the last Office action because: Applicant’s instant claims presently embrace a pharmaceutical composition comprising the combination of any compound from the full scope of the genus of compounds of General Formula [1] in combination with a b-lactamase inhibitor selected from SBT, TAZ, CVA, AVI, NAC, ZID, and VAB, for treating any gram-negative bacteria.
However, the claim amendments of March 3, 2026 are not commensurate in scope with the unexpectedly beneficial results shown in Test Examples 6 and 9 of the Specification. The claimed genus of compounds of General Formula [1] and the genus of b-lactamase inhibitors are not limited to the superior antibacterial effects and criticality demonstrated in Test Examples 6 and 9 of the Specification: Test Example 6 demonstrates the antibacterial activity of the combinations of just five compound species of General Formula [1] with each of the recited b-lactamase inhibitors: i.e., each of Compound A, Compound B, Compound C, Compound D, and Compound E, in combination with each of the seven b-lactamase inhibitors sulbactam (SBT), tazobactam (TAZ), clavulanic acid (CVA), avibactam (AVI), nacubactam (NAC), zidebactam (ZID), and vaborbactam (VAB), at a concentration of 4 ug/mL, against strains of just two types of gram-negative bacteria, E. coli and K. pneumoniae, see Tables 43-47 (pages 236-242). Test Example 9 demonstrates the antibacterial activity of the combinations of just two compound species of General Formula [1] with each of the above-named b-lactamase inhibitors: each of Compound F and Compound G in combination with each of the seven b-lactamase inhibitors SBT, TAZ, CVA, AVI, NAC, ZID, and VAB, at a concentration of 4 ug/mL, against strains of just two types of gram-negative bacteria, E. coli and K. pneumoniae, see Tables 51 and 52 (pages 244-245).
22.
Previous Double Patenting Rejections
7. 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).
8. 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).
9. 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.
10. The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
11. Claims 1 and 17 remain rejected, and claims 36 and 37 are newly rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of copending U.S. Application No. 17/063,110, now U.S. Pat. No. 12,286,440 B2, in view of Bush et al., Cold Spring Harb Perspect Med (2016).
12. This rejection has been modified as necessitated by Applicant’s amendment to the claims.
Claim 1, as amended, recites a pharmaceutical composition comprising a penam compound of General Formula [1] or a salt thereof:
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, wherein:
R1 and R3 are each hydrogen; R2 is phenyl optionally substituted by one or more substituents selected from hydroxy or halogen; X1 is a C1-6 alkylene group or a divalent cyclic hydrocarbon group; A is 2-aminothiazol-4-yl group optionally substituted by halogen; Q is a divalent piperazine or pyrrolidine which may be substituted with oxo groups; Y1, Y2 and X3 are each a bond; X2 is -NR4b- wherein R4b is hydrogen; and Y3 is –C(=O)-C(=O)-; in combination with:
one or more b-lactamase inhibitor(s) selected from avibactam, nacubactam, zidebactam, vaborbactam, sulbactam, tazobactam, and clavulanic acid;
for use in treating infections caused by Gram-negative bacteria (claim 17).
Claim 36 is drawn to claim 1 and limits the compound of General Formula [1] or a salt thereof to Compound A, B, C, D or E or a salt thereof:
Compound A: (3R,5R,6R)-6-((Z)-2-(2-aminothiazol-4-yl)-2-(((2-carboxypropan-2- yl)oxy)imino)acetamido)-3 -(3 -(2-(2-chloro-3,4-dihydroxyphenyl)-2-oxoacetamido)-2- oxoimidazolidin-1-yl)-7-oxo-4-thia-1-azabicyclo[3.2.0]-heptane-3-carboxylic acid (claim 37);
Compound B: (3R,5R,6R)-6-((Z)-2-(2-aminothiazol-4-yl)-2-((1- carboxycyclobutoxy)imino)acetamido)-3 -(3 -(2-(2-chloro-3,4-dihydroxyphenyl)-2- oxoacetamido)-2-oxoimidazolidin-1-yl)-7-oxo-4-thia-1-azabicyclo[3.2.0]-heptane-3-carboxylic acid;
Compound C: (3R,5R,6R)-6-((Z)-2-(2-aminothiazol-4-yl)-2-(((2-carboxypropan- 2-yl)oxy)imino)acetamido)-3 -(4-(2-(2-chloro-3,4-dihydroxyphenyl)-2-oxoacetamido)-2,3- dioxopiperazin-1-yl)-7-oxo-4-thia-1-azabicyclo[3.2.0]-heptane-3-carboxylic acid;
Compound D: (3R,5R,6R)-6-((Z)-2-(2-amino-5-chlorothiazol-4-yl)-2-(((2- carboxypropan-2-yl)oxy)imino)acetamido)-3 -(3 -(2-(2-chloro-3,4-dihydroxyphenyl)-2- oxoacetamido)-2-oxoimidazolidin-1-yl)-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-3-carboxylic acid; or
Compound E: (3R,5R,6R)-6-((Z)-2-(2-aminothiazol-4-yl)-2-((1- carboxycyclopropoxy)imino)acetamido)-3 -(3 -(2-(2-chloro-3,4-dihydroxyphenyl)-2- oxoacetamido)-2-oxoimidazolidin-1-yl)-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-3-carboxylic acid.
13. The claims of U.S. Pat. No. 12,286,440 B2 are as follows:
Claim 1. A compound represented by General Formula [1] or a salt thereof:
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.
Claim 2. The compound or a salt thereof according to claim 1, wherein R2 represents an aryl group which may be substituted.
Claim 3. The compound or a salt thereof according to claim 1, wherein A represents a monocyclic heterocyclic group which may be substituted.
Claim 4. The compound or a salt thereof according to claim 1, wherein X1 represents a C1-6 alkylene group which may be substituted or a divalent cyclic hydrocarbon group which may be substituted.
Claim 5. The compound or a salt thereof according to claim 1, wherein Q represents a divalent heterocyclic group which may be substituted.
Claim 6. The compound or a salt thereof according to claim 1, wherein Y1 represents a C1-6 alkylene group which may be substituted, a group represented by Formula —N═CH—CH═N—, a group represented by Formula —N═CH—CH2—, a group represented by Formula —N═CHC(═O)—, a group represented by Formula —NHC(═O)—, a group represented by Formula —NHC(═O)CH2—, a group represented by Formula —NHC(═O)NH—, a group represented by Formula —NHC(═O)NH—O—, a group represented by Formula —NHC(═O)C(═O)NH—, a group represented by Formula —NHCH.sub.2C(═O)—, or a bond.
Claim 7. The compound or a salt thereof according to claim 1, wherein X2 represents a group represented by General Formula —NR4a— (where R4a represents a hydrogen atom or a carbamoyl group), a group represented by General Formula —N*R5aR6a— (where R5a and R6a in combination represent a C2-6 alkylene group which may be substituted), a group represented by General Formula —NR7a—C(═O)—NR8a— (where R7a and R8a each represent a hydrogen atom), a divalent cyclic amino group which may be substituted, a divalent heterocyclic group which may be substituted, or a bond.
Claim 8. The compound or a salt thereof according to claim 1, wherein Y2 represents a C1-6 alkylene group which may be substituted or a bond.
Claim 9. The compound or a salt thereof according to claim 1, wherein X3 represents a group represented by General Formula —NR9a— (where R9a represents a hydrogen atom) or a bond.
Claim 10. The compound or a salt thereof according to claim 1, wherein R3 represents a hydrogen atom.
Claim 11. The compound or a salt thereof according to claim 1, wherein R1 represents a hydrogen atom.
Claim 12. The compound or a salt thereof according to claim 1, wherein R2 represents a phenyl group which may be substituted; A represents a monocyclic nitrogen and sulfur-containing heterocyclic group which may be substituted; Q represents a divalent monocyclic heterocyclic group which may be substituted; Y1 represents a group represented by Formula —NHC(═O)—, a group represented by Formula —NHC(═O)C(═O)NH—, or a bond; X2 represents a group represented by General Formula —N4b— (where R4b represents a hydrogen atom) or a bond; Y2 represents a C1-3 alkylene group or a bond; and Y3 represents a group represented by Formula —C(═O)— or a group represented by Formula —C(═O)—C(═O)—.
Claim 13. The compound or a salt thereof according to claim 1, wherein the compound is a compound selected from:
(3R,5R,6R)-6-((Z)-2-(2-aminothiazol-4-yl)-2-((1-carboxycyclobutoxy)imino)-acetamido)-3-(3-(2-(2-chloro-3,4-dihydroxyphenyl)-2-oxoacetamido)-2-oxoimidazolidin-1-yl)-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-3-carboxylate;
(3R,5R,6R)-6-((Z)-2-(2-aminothiazol-4-yl)-2-(((2-carboxypropan-2-yl)oxy)imino)-acetamido)-3-(3-(2-(2-chloro-3,4-dihydroxyphenyl)-2-oxoacetamido)-2-oxoimidazolidin-1-yl)-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-3-carboxylate;
(3R,5R,6R)-6-((Z)-2-(2-amino-5-chlorothiazol-4-yl)-2-(((2-carboxypropan-2-yl)oxy)imino)acetamido)-3-(3-(2-(2-chloro-3,4-dihydroxyphenyl)-2-oxoacetamido)-2-oxoimidazolidin-1-yl)-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-3-carboxylate; (3R,5R,6R)-6-((Z)-2-(2-aminothiazol-4-yl)-2-(((2-carboxypropan-2-yl)oxy)imino)acetamido)-3-((S)-3-(2-(2-chloro-3,4-dihydroxyphenyl)-2-oxoacetamido)-2-oxopyrrolidin-1-yl)-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-3-carboxylate; (3R,5R,6R)-6-((Z)-2-(2-aminothiazol-4-yl)-2-(((2-carboxypropan-2-yl)oxy)imino)-acetamido)-3-((R)-3-(2-(2-chloro-3,4-dihydroxyphenyl)-2-oxoacetamido)-2-oxopyrrolidin-1-yl)-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-3-carboxylate;
(3R,5R,6R)-6-((Z)-2-(2-aminothiazol-4-yl)-2-(((2-carboxypropan-2-yl)oxy)imino)acetamido)-3-(4-(2-(2-chloro-3,4-dihydroxyphenyl)-2-oxoacetatamido)-2,3-dioxopiperazin-1-yl)-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-3-carboxylate; and (3R,5R,6R)-6-((Z)-2-(2-amino-5-chlorothiazol-4-yl)-2-(((2-carboxypropan-2-yl)oxy)imino)acetamido)-3-(3-(2-(2-(2-(2-chloro-3,4-dihydroxyphenyl)-2-oxoacetyl)hydradienyl)-2-oxoacetamido)-2-oxoimidazolidin-1-yl)-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-3-carboxylate.
Claim 14. A pharmaceutical composition comprising: the compound or a salt thereof according to claim 1.
14. As such, U.S. Pat. No. 12,286,440 B2 recites a pharmaceutical composition comprising a genus of penam compounds having antibacterial activity that fully embrace Applicant’s instant genus of General Formula (1), wherein in patented Claim 13, the first compound species recited is the same as Applicant’s instantly recited Compound B, the second compound species recited is the same as instant Compound A, the third compound species recited is the same as instant Compound D, and the fourth compound species recited is the same as Applicant’s instant Compound C.
15. U.S. Pat. No. 12,286,440 B2 is silent to an additional b-lactamase inhibitor.
16. Yet, Bush et al. teach the advantages of combining b-lactamase inhibitors with penam antibiotics, namely, counteracting resistance to b-lactams:
“The most prevalent and most damaging resistance mechanisms among Gram-negative pathogens are represented by the b-lactamases (Babic et al. 2006; Livermore 2012), both chromosomally encoded enzymes that may be produced at high levels and transferable enzymes that travel on mobile elements among species (Bush 2013). When these targeted mechanisms are combined with decreased uptake or increased efflux of the b-lactam, high-level resistance becomes a major clinical problem (see Bonomo 2016). Perhaps the most encouraging prospect in counteracting resistance is the emergence of new classes of b-lactamase inhibitors that will provide protection for some of the most valuable antibiotics in clinical practice,”
(Page 17, right column, last paragraph).
Bush et al. go on to specifically name b-lactamase inhibitors including clavulanic acid, sulbactam, tazobactam, avibactam, etc. (see page 15 under “b-Lactamase Inhibitors” and see Table 6, page 16).
17. Thus, one of skill in the art at the time of filing would have been motivated to combine a penam of General Formula [1] recited in U.S. Pat. No. 12,286,440, wherein the compounds specifically recited in Claim 13 are the same as Applicant’s instantly Compounds A, B, C and D, with a b-lactamase inhibitor specifically named by Bush et al., to circumvent resistance to b-lactam (i.e., penam) antibiotics, therefore achieving an additive effect for treating bacterial infections.
Response to Arguments
18. Applicant traverses the previous double patenting rejection, arguing that the reasons why the present pharmaceutical composition is not merely an obvious
variant of any pharmaceutical composition claimed in the '440 patent, either alone or in view of Bush et al, are explained in the Declaration Under 37 C.F.R. § 1.132 of Muneo Shoji.
Mr. Shoji notes that the genus of compounds of Formula [1] in claim 1 is “a tiny subset of the compounds included in the scope of Formula [1] of claim 1 of the '440 patent,” wherein claim 36 recites five compounds of Formula [1], each of which was employed in the working Examples (namely, Compounds A, B, C, D and E), and the claims are limited to a small set of seven b-lactamase inhibitory compounds employed in the working Examples, namely, avibactam (AVI), nacubactam (NAC), zidebactam (ZID), vaborbactam (VAB), sulbactam (SBT), tazobactam (TAZ), and clavulanic acid (CVA). (Declaration at page 2). Mr. Shoji's opinion is that the combination of a specific compound of General Formula [1] or a salt thereof with one or more of the seven specific b-lactamase inhibitory compounds recited in claim 1 is non-obvious over the '440 patent's claims in view of Bush et al., (Declaration at 3). Mr Shoji alleges that '440 patent's claim 14 recites "A pharmaceutical composition comprising: the
compound or a salt thereof according to claim 1", but does not disclose any other element of the composition.
Regarding the Bush et al. reference, Mr. Shoji states, despite the "thousands of new penicillin derivatives and related [drugs]" developed over the past 100 years, and the promise of b-lactamase inhibitors, development of which is said to have started in the mid-1970's, as a practical matter, the actual combinations which are or have been used are quite specific. (Declaration at pages 3-4). Bush et al. state that "Following a hiatus of approximately two decades, a unique class of non-(b-lactam b-lactamase inhibitors emerged... ." They state that avibactam, the first of these, "has been approved for therapeutic use in combination with ceftazidime, and is under development for ceftaroline-avibactam or aztreonam-avibactam combinations."
Applicant argues that the specific nature of the particular combinations employed shows that while benefits of employing specific b-lactamase inhibitors in certain combinations with specific b-lactams have been recognized, the art is unpredictable and a person of ordinary skill would not have been motivated based on Bush to employ the specific compounds of Formula [1] of present claim 1 with the specific b-lactamase inhibitors recited in the claim, let alone with a reasonable expectation of success in achieving an additive effect for treating bacterial infections by combining the specific Formula [1] compounds and specific (b-lactamase inhibitors recited in claim 1. (Declaration at pages 4-5).
Thus, Mr. Shoji states that even if Bush et al did provide such motivation, a person of ordinary skill in the art would not have a reasonable expectation of success in achieving an additive effect for treating bacterial infections by combining the specific Formula [1] compounds and specific b-lactamase inhibitors recited in claim 1. Id. Mr. Shoji states this is particularly the case since the compounds of General Formula [1] of the present application do not have a penicillanic acid skeleton like Bush et al's compounds, but belong to a different class of compounds having a 2-carboxypenam skeleton. Id. Mr. Shoji alleges that the present pharmaceutical composition provides
superior results which would not have been expected from the '440 patent's claims or from Bush et al. Id. at 5-9. Test Examples 6 to 9 illustrate the superior results obtained with the pharmaceutical composition of the invention. Test Example 6 evaluated antibacterial activity exhibited where Test Compounds A to E recited in claim 36 and the seven 3-lactamase inhibitors recited in claim 1 were used in combination (results are shown in Tables 43 to 47). Mr. Shoji states that they are remarkable, showing higher antibacterial activity where Compounds A, B, C, D, and E and specific inhibitors were used in combination. Declaration at 6. Test Example 7 evaluated antibacterial activity where a plurality of 3-lactamase inhibitors (SBT and AVI) and Test Compounds A and B were used in combination. The results are reported in Tables 48 and 49, and again they were excellent. See id. Test Example 8 evaluated antibacterial activity for a variety of compounds (those of Examples 143 and 147) in the same manner as Test Example 1. The results are shown in Table 50. Finally, Test Example 9 evaluated antibacterial activity in the same manner as Test Example 6, but using Test Compound F. The results are shown in Table 51. Mr. Shoji summarizes the bacterial strains A to F employed in the Test Examples as follows:
Strain A: Escherichia coli TK-1747 strain producing CTX-M-15.
Strain B: Klebsiella pneumoniae Y-1020 strain producing KPC-3 and SHV-12. Strain C: Klebsiella pneumoniae Y-1133 strain producing NDM-1, OXA-48, and CTX- M-15.
Strain D: Escherichia coli TK-3113 strain producing IMP-8.
Strain E: Escherichia coli TK-1765 strain producing CMY-2.
Strain F: Klebsiella pneumoniae Y-1069 strain producing OXA-48 and CTX-M- 15.
Mr. Shoji argues that the compounds of General Formula [1] of the present invention are “rare compounds which exhibit effective MIC values as a single agent even against highly resistant bacteria for which conventional b-lactam antibiotics are ineffective.” (Declaration at page 7). Mr. Shoji argues that when used in combination with the specific b-lactamase inhibitors recited in the present claims, they demonstrate unexpectedly superior results, reducing the MIC by a factor of 2 to over 266. See id., citing the results of Test Example 6 (Tables 43 to 47). Mr. Shoji states that the data in Test Examples 6 to 9 are representative of the full scope of the pharmaceutical composition as presently claimed. Declaration at 7-8.1 Each of the seven b-lactamase inhibitors was employed in Test Examples.
With regard to the other compounds of General Formula [1], Mr. Shoji states that the test data are also representative of the full scope of claim 1. (Declaration at page 8 ). In this regard, he notes, the genus of Formula [1] compounds in claim 1 is quite small, i.e., Mr. Shoji states there is only a handful of compounds in the "genus" of claim 1. In his opinion, persons skilled in the art would recognize the Test Compounds A to F and the compounds of Examples 143 and 147 employed in Test Examples 6 to 9 as being representative of this small set of compounds in the context of the present invention. Id.
Mr. Shoji states that the evidence of superior results shown in Text Examples 6 to 9 further supports the non-obviousness of the present claims over the claims the '440 patent in view of Bush et al. Nothing in the '440 patent's claims suggest that employing the specific compounds of Formula [1] recited here, in combination with one or more of the specific b-lactamase inhibitors recited in claim 1, would result in the dramatically higher antibacterial activity seen here. Declaration at 8. And while Bush et al provides an overview of b-lactams and inhibitors, it also illustrates the unpredictability of the art, and does not suggest that a pharmaceutical composition employing the specific compounds of Formula [1] in combination with the specific b-lactamase inhibitors recited in the claims, would provide dramatically higher antibacterial activity. Id. at 8-9.
19. Applicant's arguments have been fully considered but they are not persuasive. Regarding Applicant’s allegation that the amended claims are “now limited to the scope of combinations where desirable effects were actually demonstrated,” the claim amendments of March 3, 2026 are still not commensurate in scope with the unexpectedly beneficial results shown in Test Examples 6 and 9. The claimed genus of compounds of General Formula [1] and the genus of b-lactamase inhibitors are not limited to the superior antibacterial effects and criticality demonstrated in Test Examples 6 and 9 of the Specification.
20. Test Example 6 demonstrates the antibacterial activity of the combinations of just five compound species of General Formula [1] with each of the recited b-lactamase inhibitors: i.e., each of Compound A, Compound B, Compound C, Compound D, and Compound E, in combination with each of the seven b-lactamase inhibitors sulbactam (SBT), tazobactam (TAZ), clavulanic acid (CVA), avibactam (AVI), nacubactam (NAC), zidebactam (ZID), and vaborbactam (VAB), at a concentration of 4 ug/mL, against strains of just two types of gram-negative bacteria, E. coli and K. pneumoniae, see Tables 43-47 (pages 236-242).
21. Test Example 9 demonstrates the antibacterial activity of the combinations of just two compound species of General Formula [1] with each of the above-named b-lactamase inhibitors: each of Compound F and Compound G in combination with each of the seven b-lactamase inhibitors SBT, TAZ, CVA, AVI, NAC, ZID, and VAB, at a concentration of 4 ug/mL, against strains of just two types of gram-negative bacteria, E. coli and K. pneumoniae, see Tables 51 and 52 (pages 244-245).
22. Applicant’s instant claims presently embrace the combination of any compound from the full scope of the genus of compounds of General Formula [1] in combination with a b-lactamase inhibitor selected from SBT, TAZ, CVA, AVI, NAC, ZID, and VAB.
Regarding the “quite small” size of Applicant’s instantly recited genus, and the subgenus of five compounds recited in new claim 36 (Compounds A-E) and claim 37 (Compound A), it is noted that claim 13 of U.S. 12,286,440 B2 specifically recites Applicant’s instant Compounds A, B, C, and D within the seven compounds listed. Thus, considering that claim 13 of U.S. 12,286,440 B2 recites only seven specific compounds, the skilled artisan would have immediately envisaged selecting Applicant’s Compound A, B, C, or D for use in combination with a b-lactamase inhibitor, with a reasonable expectation of success.
23. As such, the instant claims are not limited to the scope of combinations of which “desirable effects were actually demonstrated” in the Specification and thus are not sufficiently distinguished from the combination of penam compounds recited by U.S. Pat. No. 12,286,440 in view of Bush et al. One skilled in the art would have been guided by the combined teachings of the prior art to select a penam compound from Claim 13 of U.S. 12,286,440 B2 to combine with a b-lactamase inhibitor as specifically guided by Bush et al., in order to obtain an improved antibacterial composition for the treatment of E. coli and K. pneumoniae infections, with a reasonable expectation of success.
24. Claims 1, 13 and 17 were previously rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Pat. No. 12,286,440 B2, in view of Jiao et al., Antimicrobial Agents and Chemotherapy (2019).
25. In view of Applicant’s amendment to claim 1 to delete the limitation of the antibacterial agent (as well as the genus of antibacterial agents), the previous nonstatutory double patenting rejection is withdrawn.
Conclusion
26. Claims 1, 17-34, 36 and 37 are present in the application. Claims 18-34 are withdrawn. Claims 1, 17, 36 and 37 are rejected. No claim is currently allowable.
27. THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Correspondence
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/JANET L COPPINS/Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628
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