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 .
Response to Amendment
2. Applicant’s amendment and response, submitted April 2, 2026, has been reviewed by the examiner and entered of record in the file. Claim 1 is canceled. Claims 2-11, 14, 17, 19 and 20 are amended.
3. Claims 2-20 are under examination and are the subject of this office action.
Information Disclosure Statement
4. The information disclosure statement (IDS) submitted on April 2, 2026 is in compliance with the provisions of 37 CFR 1.97 and has been considered by the examiner. Please refer to the signed copy of Applicant’s PTO-1449 form, attached herewith.
Previous Claim Rejections - 35 USC § 112(a)
5. Claims 2, 3 and 5-20 remain 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 potentiating the activity of aztreonam (Table 1) tigemonam (Table 2), biapenem (Table 3), and meropenem (Table 4) for inhibiting the growth of certain bacterial strains overexpressing class A, class B, class C, and/or class D b-lactamases, in particular Acinetobacter baumannii, Enterobacter cloacae and Klebsiella pneumoniae, comprising administering a compound species selected from Compound 1-Compound 17, was not considered enabled for a method of treating the full scope of bacterial infections embraced by the claims, comprising administering all of the other compound species presently encompassed by Formula (I) and Formula (II). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
This rejection has been modified as necessitated by Applicant’s amendment to the claims.
6. The standard for determining whether the Specification meets the enablement requirement was cast in the Supreme Court decision of Mineral Separation v. Hyde, 242 U.S. 261 (1916) which postured the question: is the experimentation needed to practice the invention undue or unreasonable? As recognized by the court in In re Wands, 858 F.2d 731 (Fed. Cir. 1988), that is still the standard to be applied, determined by consideration of the Wands factors (MPEP 2164.01(A)); namely, nature of the invention, breadth of the claims, guidance of the specification, the existence of working examples, state of the art, predictability of the art and the amount of experimentation necessary. All of the Wands factors have been considered, with the most relevant factors discussed below
7. Nature of the Invention: As stated in MPEP 2164.05(a), “[t]he initial inquiry” for determining whether the Specification is enabling “is into the nature of the invention, i.e., the subject matter to which the claimed invention pertains.”
In the instant case, the claimed invention pertains to a method of treating a bacterial infection caused by a bacteria selected from Acinetobacter baumannii, Enterobacter cloacae and Klebsiella pneumoniae, comprising administering to a subject in need thereof, one or more boronic acid compound(s) according to the structure of Formula (I), the structure of Formula (II), or a pharmaceutically acceptable salt thereof, which are alleged by the Specification to have -lactamase inhibitory activity.
8. The State of the Prior Art and the Relative Skill of those in the Art: As stated in MPEP 2164.05(a), “[t]he state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains” and, as stated in MPEP 2164.05(b), “[t]he relative skill of those in the art refers to the skill of those in the art in relation to the subject matter to which the claimed invention pertains at the time the application was filed.”
9. As discussed above, the instantly claimed invention pertains to method of treating a bacterial infection caused by a bacteria selected from Acinetobacter baumannii, Enterobacter cloacae and Klebsiella pneumoniae, comprising administering to a subject in need thereof, one or more compound(s) of Formula (I) or Formula (II), which are alleged by the Specification to have -lactamase inhibitory activity. At the time the instant application was filed, it would have been known by those of ordinary skill in the art that - due in large part to the strict requirement of complementarity between a compound and its corresponding binding site on a target receptor or enzyme - compounds, in the vast majority of cases, demonstrate a remarkably high correlation between their structure, specificity and ability to produce a pharmacological effect. At the same time, it would have also been generally assumed that two compounds with similar chemical properties would exhibit similar biological effects. Thus, given a series of compounds that are shown to exert an activity of interest (or given a target of interest), the ordinarily skilled artisan would have expected that a limited genus of related compounds (e.g., compounds exhibiting near equal molecular shapes and volumes, approximately the same distribution of electrons, and similar physical properties such as hydrophobicity, etc.) would interact with the given target to elicit a related biological response.
10. The state of the art regarding treatment of a bacterial infection caused by a bacterial organism selected from the group consisting of Acinetobacter baumannii, Enterobacter cloacae and Klebsiella pneumoniae, is that “bacterial infection,” without limitation, embraces an extremely wide spectrum of infections caused by bacterial growth wherein Acinetobacter baumannii infections manifest as urinary, wound and respiratory tract infections, nosocomial pneumonia, sepsis, soft tissue infections and meningitis. Due to its frequent insensitivity to common antibiotics, Acinetobacter baumannii has developed into a "problem germ” and is currently known as one of the most dangerous bacteria. Enterobacter cloacae infections manifest as bloodstream infections (bacteremia or sepsis), respiratory infections, pneumonia, urinary tract infections, wound infections and meningitis. Klebsiella pneumoniae bacteria are found in the upper respiratory tract and the digestive tract, and are common pathogens for bacterial sepsis, pneumonia and infections of the urinary tract or soft tissues. Klebsiella pneumoniae are highly resistant to antibiotics and are the cause of postoperative wound and blood flow infections in patients in hospitals (see webpage printouts of Acinetobacter baumannii: symptoms | transferability | prevention |, Enterobacter cloacae: symptoms | transmission | treatment | L&R Prevent and Protect, and Klebsiella pneumoniae: symptoms | transmission | treatment | L&R Prevent and Protect). Most bacterial infections are treated by administering an antibiotic, however the bacterial pathogens discussed above (and recited by the claims) are problematic and unpredictable to treat, as they are highly resistant to treatment with known antibiotics. Most antibiotics are designed to have clinically useful activity against a few types of bacteria by targeting specific pathways (see Singh et al. 2017, Table 1 at page 65). While some antibiotics have a broader spectrum of activity than others, their activity is still limited to certain bacterial strains and no single antibiotic or b-lactamase inhibitor is effective against all types and kinds of bacterial infections in a subject, i.e., no antibiotic exists that kills or inhibits the growth of all harmful bacteria in a host, regardless of site of infection without affecting beneficial gut microbes (gut flora) or causing undue toxicity to the host (Singh et al., abstract).
11. Accordingly, at the time the invention was made, the relative skill of those in the art tasked with identifying compounds exerting an activity of interest would have been high, as the ordinarily skilled artisan would have had, at minimum, a Ph.D. and experience with screening techniques including computer assisted virtual screening techniques such as ligand-based and structure-based design methods.
12. The Level of Predictability in the Art: Once a compound has been identified by ligand based and/or structure-based drug design methods as potentially binding to the target molecule, it must be evaluated. However, as discussed by Anderson (Chem and Biol 10:787-797, 2003), “it is important to consider that the ranking assigned by the scoring function is not always indicative of a true binding constant, since the model of the target:ligand interaction is inherently an approximation. Usually, several molecules which scored well during the docking run are evaluated in further tests since even the top scoring molecule could fail in vitro assays… Finally, leads are brought into the wet lab for biochemical evaluation” (Page 794, Column 1). By that point, as noted by Thiel (Nature Biotechnol 2:513-519, 2004), “libraries are small and hit rates are on the order of one in ten” (Page 517, Column 2). This low level of predictability is not surprising considering that even minor structural changes can, and frequently will, drastically alter or eradicate a parent compound’s ability to modulate the activity of a specific receptor or enzyme. Indeed, modifying even a single atom in a compound can dramatically change the compound’s overall structure and - even though complementarity in one portion of the compound might be improved by the chemical revision - the overall binding or activity might be severely compromised. This is certainly true in the case of -lactamase inhibitors which, as disclosed by Drawz and Bonomo (Clin Microbiol Rev 2010, cited on Applicant’s IDS of May 15, 2024), demonstrate significantly altered activity following minor modifications, i.e.:
“The efficacy of the mechanism-based inhibitors can vary within and between the classes of-lactamases (Table 2). For class A, SHV-1 is more resistant to inactivation by sulbactam than TEM-1 but more susceptible to inactivation by clavulanate (328). Comparative studies of TEM-and SHV-derived enzymes, including ESBLs, found that the IC50s for clavulanate were 60- and 580- fold lower than those for sulbactam against TEM-1 and SHV-1, respectively (328). In our opinion, the explanations for these differences in inactivation chemistry are likely subtle, yet highly important, differences in the enzyme active sites,”
(page 169, right column, last paragraph).
13. And, the treatment of bacterial infections with antibiotics has become less predictable with the development of bacterial resistance, resulting in limited treatment options:
“Antibiotics… have a relatively short useful lifespan due to acquired resistance [6]. So a specific ideal antibiotic will always be transitory and will have to be replaced by newer ones when older ones become ineffective. Drug discovery teams almost always want to develop an ideal antibiotic but invariably hit a variety of roadblocks, mostly scientific, which they cannot overcome, resulting in development of imperfect but generally safe antibiotic.… Resistance mechanisms can include modification of the target to alter drug-binding, production of alternate mechanisms to perform the function of the target, inactivation of the drug, reduction of drug entry and expression of efflux pumps to eliminate drugs from inside bacterial cells [8]. In certain cases bacteria are not only resistant to one class of antibiotics but to several classes simultaneously, significantly limiting treatment options.”
(Singh et al., page 64, left column, third and fourth paragraphs).
14. The Amount of Direction Provided by the Inventor / Existence of Working Examples: The amount of direction provided by the Applicant is considered to be determined by the Specification and the working examples. In the instant case, the Specification discloses the -lactamase inhibitory activity of just 17 compound species encompassed by Formula (Ic), wherein said Compounds 1-17 potentiate the activity of aztreonam (Table 1), tigemonam (Table 2), biapenem (Table 3), and meropenem (Table 4), for inhibiting the growth of certain bacterial strains overexpressing class A, class B, class C, and/or class D b-lactamases in vitro, (see Examples 17-20, pages 79-83). The specification fails to teach the antibacterial activity of any compound species of any compound species of Formula (IIc). The Specification demonstrates the in vitro activity of Compounds 1-17 against the bacterial organisms Enterobacter cloacae and Klebsiella pneumoniae (Examples 17 and 18) and Acinetobacter baumannii (Example 20), but fails to demonstrate therapeutic efficacy of any other compound(s) of Formula (Ic) or (IIc) for the treatment of said bacterial infection(s) in a subject in need thereof.
15. Scope or Breadth of the Claims: As stated in MPEP 2164.01(c), “[w]hen a compound or composition claim is limited by a particular use, enablement of that claim should be evaluated based on that limitation.” Thus, as stated in MPEP 2164.08, “[t]he focus of the examination inquiry is whether everything within the scope of the claim is enabled” (emphasis added). The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation’.” In re Wright, 999 F.2d 1557 (Fed. Cir. 1993) (emphasis added).
16. At the same time, however, it is also recognized that not everything necessary to practice the invention need be disclosed. Accordingly, for purposes of enablement, the relevant concern is whether the scope of enablement provided to one skilled in the art by the disclosure is commensurate in scope with the protection sought by the claims. Thus, while “a patent application is entitled to claim his invention generically” it is necessary that “he provide a disclosure sufficient to enable one skilled in the art to carry out the invention commensurate with the scope of his claims". Amgen, Inc, v. Chugai Pharmaceutical Co., Ltd. (Fed. Cir. 1991). As noted by the court in In re Fisher, 427 F.2d 833 (CCPA 1970), the scope of enablement must bear a “reasonable correlation” to the scope of the claims. See also Ak Steel Corp. v. Sollac, 344 F.3d 1234 (Fed. Cir. 2003) and In re Moore, 439 F.2d 1232 (CCPA 1971). As stated in MPEP 2164.08, resolution of this concern requires two stages of inquiry: “[t]he first is to determine how broad the claim is with respect to the disclosure. The entire claim must be considered. The second inquiry is to determine if one skilled in the art is enabled to make and use the entire scope of the claim without undue experimentation”.
17. As to the first inquiry, as discussed above, the claims are drawn to a method of treating a bacterial infection comprising administering to a subject in need thereof one or more compounds of Formula (Ic) and/or Formula (IIc), which are alleged by the Specification to act as -lactamase inhibitors. Considering that Formulae (Ic) and (IIc) combined encompass thousands of compound species, the claims are broad with substantial variance. Yet, as discussed above, the instant Specification discloses the bactericidal activity of only 17 compound species encompassed by Formula (Ic) as recited by the claims, and fails to disclose any compound species of Formula (IIc).
18. As such, the claims are broad with respect to the disclosure. The second inquiry is discussed in detail below.
19. Amount of Experimentation Necessary: In view of all of the foregoing, at the time the invention was made, it would have required undue experimentation to practice the entire scope of the invention as claimed. As discussed above, the claims are drawn to a method of treating any types of bacterial infection caused by Acinetobacter baumannii, Enterobacter cloacae, and Klebsiella pneumoniae, without limitation, comprising administering to a subject in need thereof one or more compounds of Formula (Ic) and/or Formula (IIc). Since identifying any compound which is capable of modulating the activity of a specific receptor, ion channel, or enzyme is extremely complex, the nature of the instant invention considered to be one of extreme complexity. In the instant case, this complexity is exacerbated by the broadness of Formulae (Ic) and (IIc) with respect to the disclosure, because said Formulae each encompass hundreds of compound species, and potentially thousands of compound species, whereas the instant Specification demonstrates only 17 such compound species of Formula (Ic) exerting antibacterial activity, and fails to disclose the activity of any compound(s) of Formula (IIc). Although the relative skill of those in the art to which the invention pertains is high, the state of the art and unpredictability within the art is such that even the most talented artisan (armed with screening techniques including computer assisted virtual screening techniques such as ligand-based and structure-based design methods) could not reasonably predict which of the hundreds or thousands of compounds encompassed by Formulae (Ic) and (IIc) would exert the alleged activity for treating the full scope of bacterial infections embraced by the claims, based on the limited disclosure of 17 active compounds.
Given the unpredictability of -lactamase inhibitors discussed by Drawz and Bonomo, it is highly unpredictable whether any compound species within the subgenus of compounds of Formula (Ic) identified by rational drug design based on the instant disclosure would be usable for the types and kinds if bacterial infections embraced by the claims. Whether compounds other than 1-17 of Formula (Ic), let alone compounds of Formula (IIc) would be effective against the full scope of bacterial infections embraced the claims is even less predictable. As such, the only way to ascertain which of the hundreds and potentially thousands, of claimed compounds encompassed by Formula (Ic) and Formula (IIc) are usable based on the limited disclosure would require undue experimentation.
20. While Applicant’s amendatory changes limit the bacterial infections to be treated to infections caused by Acinetobacter baumannii, Enterobacter cloacae and Klebsiella pneumoniae, the scope of compounds to be administered comprising a compound of Formula (Ic) or Formula (IIc) is not commensurate in scope with the unexpected results demonstrate in the Specification.
Response to Arguments
21. Applicant states that claim 1 has been canceled and claim 2 has been amended to be in independent form and more closely correlates with the exemplified compounds. Applicant asserts that the application as filed details the preparation of all 17 compounds of claim 4, wherein the options presented for each variable in claim 2 are exemplified by at least one of the compounds of claim 4. Each of the options for the G position corresponds to at least one of the exemplified compounds. Applicant argues that because the preparation of each compound has been described in the application, Applicant submits that it would not require a person of ordinary skill in the art undue experimentation to practice the entire scope of the invention as claimed.
Regarding the Examiner’s assertion that the specification does not teach any compounds of Formula (II) (now (IIc)), Applicant alleges that although the exemplified compounds are drawn as the cyclic Formula I-type structure, as described in paragraph [0041], these compounds may convert to or exist in equilibrium with the acyclic forms depending on the medium. Claim 2 is intended to cover both the cyclic and acyclic forms of these compounds that may exist simultaneously.
Applicant states that claim 2 has been limited to the treatment of bacterial infections selected from Acinetobacter baumannii, Enterobacter cloacae, and Klebsiella pneumoniae. Applicant alleges that in addition to enabling Acinetobacter baumannii, at least Examples 17 and 18 in the specification provide in vitro data demonstrating the potentiating activity of the recited compounds for inhibiting the growth of Enterobacter cloacae and Klebsiella pneumoniae in the presence of a compound selected from Compound 1 - Compound 17.
22. Applicant's arguments have been fully considered but they are not persuasive. While Applicant’s amendatory changes limit the bacterial infections to infections caused by Acinetobacter baumannii, Enterobacter cloacae or Klebsiella pneumoniae, the scope of infections to be treated still embraces at least respiratory infections including pneumonia, blood infections, soft tissue and wound infections, urinary tract infections, and meningitis, and the scope of compounds to be administered still embraces any compound(s) of Formula (Ic) and/or Formula (IIc). Applicant has demonstrated possession of compounds 1-17, as well as their ability to potentiate aztreonam, tigemonam and meropenem against strains of Acinetobacter baumannii, Enterobacter cloacae or Klebsiella pneumoniae (i.e., the compound species recited in claim 4). However, according to MPEP 716.02(d), the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." The previous claim amendments of April 2, 2026 don’t capture Applicant’s alleged unexpected results of the administration of a compound selected from compounds 1-17 against a bacterial infection caused by Acinetobacter baumannii, Enterobacter cloacae or Klebsiella pneumoniae. Thus the examiner recommends inserting criticality from Examples 17-20 into the claims.
Previous Claim Rejections - 35 USC § 112(b)
23. Claim 14 was previously rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite regarding the parenthetical recitations in lines 2-7.
24. In view of Applicant’s amendments to delete the compounds listed in said parentheticals, the indefiniteness rejection has been overcome and is withdrawn.
Previous Claim Rejections - 35 USC § 103
25. Claims 1, 2, 4 and 11-20 were previously rejected under 35 U.S.C. 103 as being unpatentable over Reddy et al., WO 2016/149393 A1 (published September 22, 2016).
26. In view of the declaration previously submitted under § 1.132 by Dr. Scott Hecker ("Hecker Declaration I" dated September 26, 2022) in parent Application No. 17/048,052, which compares Compound 12 of the instant application with the position isomer compound of Reddy, wherein the data show that, of the 26 different strain/antibiotic combinations tested, Applicant’s Compound 12 exhibited a higher activity than the compound disclosed in Reddy in ten of the strain/antibiotic combinations, Applicant’s arguments are persuasive.
The previous obviousness rejection is withdrawn.
Previous Double Patenting Rejections
27. Claims 2-20 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 21-23 of U.S. Patent No. 9,132,140 B2.
This rejection has been modified as necessitated by Applicant’s amendment to the claims.
Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claim 2 is directed to a method of treating a bacterial infection, comprising administering to a subject in need thereof a compound of Formula (Ic) or Formula (IIc),
PNG
media_image1.png
133
408
media_image1.png
Greyscale
or a pharmaceutically acceptable salt thereof, more specifically wherein the subject is a mammal that is a human (claims 17 and 18). Claims 3-10 are drawn to claim 2, and further limit the compound species of Formula (Ic) or Formula (IIc). Claim 11 is drawn to the method of claim 2, further comprising administering an additional medicament (wherein the additional medicament is selected from the group consisting of an antibacterial agent, an antifungal agent, an antiviral agent, an anti-inflammatory agent, and an anti-allergic agent (claim 12), more specifically, a b-lactam antibacterial agent (claim 13)). Claim 14 is drawn to claim 13, wherein the β-lactam antibacterial agent is selected from the group consisting of Amoxicillin, Ampicillin, Epicillin, Carbenicillin, Ticarcillin, Temocillin, Azlocillin, Piperacillin, Mezlocillin, Mecillinam, Sulbenicillin, Benzylpenicillin, Clometocillin, Benzathine benzylpenicillin, Procaine benzylpenicillin, Azidocillin, Penamecillin, Phenoxymethylpenicillin, Propicillin, Benzathine phenoxymethyl-enicillin, Pheneticillin, Cloxacillin, Oxacillin, Meticillin, Nafcillin, Faropenem, Tomopenem, Razupenem, Cefazolin, Cefacetrile, Cefadroxil, Cefalexin, Cefaloglycin, Cefalonium, Cefaloridine, Cefalotin, Cefapirin, Cefatrizine, Cefazedone, Cefazaflur, Cefradine, Cefroxadine, Ceftezole, Cefaclor, Cefamandole, Cefminox, Cefonicid, Ceforanide, Cefotiam, Cefprozil, Cefbuperazone, Cefuroxime, Cefuzonam, Cefoxitin, Cefotetan, Cefmetazole, Loracarbef, Cefixime, Ceftriaxone, Cefcapene, Cefdaloxime, Cefdinir, Cefditoren, Cefetamet, Cefmenoxime, Cefodizime, Cefoperazone, Cefotaxime, Cefpimizole, Cefpiramide, Cefpodoxime, Cefsulodin, Cefteram, Ceftibuten, Ceftiolene, Ceftizoxime, Flomoxef, Latamoxef, Cefepime, Cefozopran, Cefpirome, Cefquinome, Ceftobiprole, Ceftaroline, CXA- 101, RWJ-54428, MC-04,546, ME1036, Ceftiofur, Cefquinome, Cefovecin, RWJ-442831, RWJ-333441, and RWJ-333442.
Claim 15 is drawn to claim 13, wherein the β-lactam antibacterial agent is selected from the group consisting of Ceftazidime, Biapenem, Doripenem, Ertapenem, Imipenem, Meropenem, Tebipenem, Tebipenem pivoxil, Apapenem, and Panipenem or selected from the group consisting of Aztreonam, Tigemonam, BAL30072, SYN 2416, and Carumonam (claim 16)).
Claim 19 is drawn to claim 2, and further limits the bacterial infection to be treated to Acinetobacter baumannii. Claim 20 is drawn to claim 2, and further limits the bacterial infection to be treated to Enterobacter cloacae, or Klebsiella pneumoniae.
28. Claim 21 of U.S. 9,132,140 B2 recites a method of treating a bacterial infection, comprising administering a boronic acid derivative of Formula (I-1) or Formula (I-2) (recited in Claim 1):
PNG
media_image2.png
198
349
media_image2.png
Greyscale
PNG
media_image3.png
136
236
media_image3.png
Greyscale
wherein “n”=0; and the other variables are as defined in the claims, which are positional isomers of Applicant’s recited species of claims 2-10. Claim 22 is drawn to Claim 21 and recites co-administering the pharmaceutical composition with an additional medicament wherein the additional medicament is selected from an antibacterial agent, an antifungal agent, an antiviral agent, an anti-inflammatory agent, or an antiallergic agent. Claim 23 is drawn to Claim 21 and recites wherein the additional medicament is a b-lactam antibacterial agent, and wherein the b-lactam antibacterial agent is selected from Ceftazidime, Biapenem, Doripenem, Ertapenem, Imipenem, Meropenem, Panipenem, Aztreonam, Tigemonam, BAL30072, SYN 2416, or Carumonam.
29. Thus, the genus of compounds recited in U.S. 9,132,140 B2 of Formula (I-I) fully embraces and only differs from Applicant’s instant genus of Formula (Ic) as positional isomers, i.e., the “Y-(CR8R9)n-G” substituent is in the ortho position relative to the -OH moiety , wherein Applicant’s “-CH2-G” substituent is in the meta position relative to the -OH moiety. The genus of compounds recited in U.S. 9,132,140 B2 of Formula (I-2) fully embraces the genus that is instantly recited by Applicant in Formula (IIc) but differs in the placement of the “G” substituent on the ethyl group, i.e., the “Y-(CR8R9)n-G” substituent is in the “2” position relative to the ring , wherein Applicant’s “-CH2-G” substituent is in the “1” position relative to the ring.
30. Yet, compounds that are position isomers (compounds having the same radicals in physically different positions on the same nucleus) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious).
31. Therefore one skilled in the art would be motivated to treat the instantly recited bacterial infections comprising administering the instantly recited positional isomers of the boronic acid derivatives previously recited in U.S. 9,132,140 B2, and would have had reasonable expectation of success that the similar compounds would have similar pharmacokinetic properties, oral availability, antimicrobial potency, and/or duration of effect, etc.
32. And, "[a]n obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) (discussed in more detail below) and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990). See MPEP § 2144 for an extensive review of the case law pertaining to obviousness based on close structural similarity of chemical compounds.
33. Regarding the comprehensive of the genus recited, a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989). See also Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005)(reference disclosing optional inclusion of a particular component teaches compositions that both do and do not contain that component); Celeritas Technologies Ltd. v. Rockwell International Corp., 150 F.3d 1354, 1361, 47 USPQ2d 1516, 1522-23 (Fed. Cir. 1998) (The court held that the prior art anticipated the claims even though it taught away from the claimed invention. "The fact that a modem with a single carrier data signal is shown to be less than optimal does not vitiate the fact that it is disclosed."). Furthermore, "[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).
34. Claim 23 of U.S. 9,132,140 B2 recites the same group of additional medicaments that are recited by Applicant in instant claim 12. And, the subgenus of additional medicaments (specifically b-lactam antibacterial agents) recited by Applicant in instant claims 15 and 16 are embraced by the genus recited in claim 23 of U.S. 9,132,140 B2.
35. Thus, one skilled in the art would have been motivated to treat a bacterial infection in a subject in need thereof comprising administering a compound of Formula (I-1) or Formula (I-2), which is/are positional isomer(s) of the genus of previously patented boronic acid derivatives of U.S. 9,132,140 B2, and would have had a reasonable expectation of success.
As such, claims 1-20 are prima facie obvious over Claims 21-23 of U.S. 9,132,140 B2.
36. Claims 2-20 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 27-37 of U.S. Patent No. 9,241,947 B2.
This rejection has been modified as necessitated by Applicant’s amendment to the claims.
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant claims are described in detail, above.
37. Claim 27 of U.S. 9,241,947 B2 recites a method of treating a bacterial infection in a mammal that is a human (claims 34 and 35) comprising administering a boronic acid derivatives of Formula (I) (recited in Claim 1):
PNG
media_image4.png
153
289
media_image4.png
Greyscale
,
having the same core structure that is instantly recited by Applicant, wherein “n”=0; and the other variables are as defined in the claims, which are positional isomers of Applicant’s recited genus of compounds recited in instant claims 2-10. Claim 28 is drawn to Claim 27 and recites co-administering the pharmaceutical composition with an additional medicament, wherein the additional medicament is selected from an antibacterial agent, an antifungal agent, an antiviral agent, an anti-inflammatory agent, or an antiallergic agent (claim 29). Claim 30 is drawn to Claim 29 and recites wherein the additional medicament is a b-lactam antibacterial agent, (more specifically wherein the b-lactam antibacterial agent is selected from Ceftazidime, Biapenem, Doripenem, Ertapenem, Imipenem, Meropenem, or Panipenem (Claim 32), or selected from Aztreonam, Tigemonam, BAL30072, SYN 2416, or Carumonam (Claim 33)). Claim 31 is drawn to claim 30, wherein the β-lactam antibacterial agent wherein the β-lactam antibacterial agent is selected from the group consisting of Amoxicillin, Ampicillin (Pivampicillin, Hetacillin, Bacampicillin, Metampicillin, Talampicillin), Epicillin, Carbenicillin (Carindacillin), Ticarcillin, Temocillin, Azlocillin, Piperacillin, Mezlocillin, Mecillinam (Pivmecillinam), Sulbenicillin, Benzylpenicillin (G), Clometocillin, Benzathine benzylpenicillin, Procaine benzylpenicillin, Azidocillin, Penamecillin, Phenoxymethylpenicillin (V), Propicillin, Benzathine phenoxymethylpenicillin, Pheneticillin, Cloxacillin (Dicloxacillin, Flucloxacillin), Oxacillin, Meticillin, Nafcillin, Faropenem, Tomopenem, Razupenem, Cefazolin, Cefacetrile, Cefadroxil, Cefalexin, Cefaloglycin, Cefalonium, Cefaloridine, Cefalotin, Cefapirin, Cefatrizine, Cefazedone, Cefazaflur, Cefradine, Cefroxadine, Ceftezole, Cefaclor, Cefamandole, Cefminox, Cefonicid, Ceforanide, Cefotiam, Cefprozil, Cefbuperazone, Cefuroxime, Cefuzonam, Cefoxitin, Cefotetan, Cefmetazole, Loracarbef, Cefixime, Ceftriaxone, Cefcapene, Cefdaloxime, Cefdinir, Cefditoren, Cefetamet, Cefmenoxime, Cefodizime, Cefoperazone, Cefotaxime, Cefpimizole, Cefpiramide, Cefpodoxime, Cefsulodin, Cefteram, Ceftibuten, Ceftiolene, Ceftizoxime, Flomoxef, Latamoxef, Cefepime, Cefozopran, Cefpirome, Cefquinome, Ceftobiprole, Ceftaroline, CXA- 101, RWJ-54428, MC-04,546, ME1036, Ceftiofur, Cefquinome, Cefovecin, RWJ-442831, RWJ-333441, and RWJ-333442.
Claim 36 is drawn to claim 27, and further limits the bacterial infection to be treated to Pseudomonas acidovorans, Pseudomonas alcaligenes, Pseudomonas putida, Burkholderia cepacia, Aeromonas hydrophilia, Francisella tularensis, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Providencia alcalifaciens, Providencia rettgeri, Providencia stuartii, Acinetobacter baumannii, Bordetella pertussis, Bordetella para pertussis, Bordetella bronchiseptica, Haemophilus ducreyi, Pasteurella multocida, Pasteurella haemolytica, Branhamella catarrhalis, Borrelia burgdorferi, Kingella, Gardnerella vaginalis, Bacteroides distasonis, Bacteroides 3452A homology group, Clostridium difficile, Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium leprae, Corynebacterium diphtheriae, Corynebacterium ulcerans, Streptococcus pneumoniae, Streptococcus agalactiae, Streptococcus pyogenes, Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Staphylococcus intermedius, Staphylococcus hyicus subsp. hyicus, Staphylococcus haemolyticus, Staphylococcus hominis, and Staphylococcus saccharolyticus. Claim 37 is drawn to claim 27, and further limits the bacterial infection to be treated to Pseudomonas aeruginosa, Pseudomonas fluorescens, Stenotrophomonas maltophilia, Escherichia coli, Citrobacter freundii, Salmonella typhimurium, Salmonella typhi, Salmonella paratyphi, Salmonella enteritidis, Shigella dysenteriae, Shigella flexneri, Shigella sonnei, Enterobacter cloacae, Enterobacter aerogenes, Klebsiella pneumoniae, Klebsiella oxytoca, Serratia marcescens, Acinetobacter calcoaceticus, Acinetobacter haemolyticus, Yersinia enterocolitica, Yersinia pestis, Yersinia pseudotuberculosis, Yersinia intermedia, Haemophilus influenzae, Haemophilus parainfluenzae, Haemophilus haemolyticus, Haemophilus parahaemolyticus, Helicobacter pylori, Campylobacter fetus, Campylobacter jejuni, Campylobacter coli, Vibrio cholerae, Vibrio parahaemolyticus, Legionella pneumophila, Listeria monocytogenes, Neisseria gonorrhoeae, Neisseria meningitidis, Moraxella, Bacteroides fragilis, Bacteroides vulgatus, Bacteroides ovalus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides eggerthii, and Bacteroides splanchnicus.
38. The genus of compounds of formula I recited in U.S. 9,241,197 B2 differ from Applicant’s recited genus of Formula (Ic) as positional isomers, i.e. the “Y-(CH2)n-G” substituent is in the ortho position relative to the -OH moiety on the boron-containing ring, wherein Applicant’s “-CH2-G” substituent is in the meta position relative to the -OH moiety on the boron-containing ring.
39. Yet, compounds that are position isomers (compounds having the same radicals in physically different positions on the same nucleus) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious). Therefore one skilled in the art would be motivated to treat a bacterial infection comprising administering the instantly recited positional isomers of the boronic acid derivatives previously recited in U.S. 9,241,197 B2, and would reasonably expect that the similar compounds would have similar pharmacokinetic properties, oral availability, antimicrobial potency, and/or duration of effect, etc.
40. And, "[a]n obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) (discussed in more detail below) and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990). See MPEP § 2144 for an extensive review of the case law pertaining to obviousness based on close structural similarity of chemical compounds.
41. Regarding the comprehensive of the genus recited, a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989). See also Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005)(reference disclosing optional inclusion of a particular component teaches compositions that both do and do not contain that component); Celeritas Technologies Ltd. v. Rockwell International Corp., 150 F.3d 1354, 1361, 47 USPQ2d 1516, 1522-23 (Fed. Cir. 1998) (The court held that the prior art anticipated the claims even though it taught away from the claimed invention. "The fact that a modem with a single carrier data signal is shown to be less than optimal does not vitiate the fact that it is disclosed."). Furthermore, "[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).
42. Claim 28 recites co-administering with an additional medicament (which embraces instant claim 11). Claims 29-30 of U.S. 9,241,947 B2 recite the same types of additional medicaments that are recited by Applicant in instant claims 12-13. And, the subgenus of additional medicaments (specifically b-lactam antibacterial agents) recited by Applicant in instant claims 15 and 16 are embraced by the genus recited in Claims 31-33 of U.S. 9,241,947 B2. Claims 36 and 37 of U.S. 9,241,947 B2 recite the same bacterial infections to be treated that are instantly recited in claims 19 and 20.
43. Thus, one skilled in the art would have been motivated to treat a bacterial infection in a subject in need thereof comprising administering a compound of instant Formula (Ic), which is a positional isomer of the genus of previously patented boronic acid derivatives of U.S. 9,241,947 B2, and would have had a reasonable expectation of success.
44. Thus, one skilled in the art would have been motivated to treat a bacterial infection in a subject in need thereof comprising administering a compound that is a positional isomer of the known genus of previously patented boronic acid derivatives, and would have had a reasonable expectation of success.
As such, claims 2-20 are prima facie obvious over claims 27-37 of U.S. 9,241,947 B2.
45. Claims 2-20 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 41-43 of U.S. Patent No. 10,206,937 B2.
This rejection has been modified as necessitated by Applicant’s amendment to the claims.
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant claims are described in detail, above.
46. Claim 41 of U.S. 10,206,937 B2 recites a method of treating a bacterial infection comprising administering a boronic acid derivatives of Formula (I-1):
PNG
media_image2.png
198
349
media_image2.png
Greyscale
,
PNG
media_image3.png
136
236
media_image3.png
Greyscale
having the same core structure that is instantly recited by Applicant, wherein “n”=0; and the other variables are as defined in the claims, which are positional isomers of Applicant’s recited genus including the compounds of claims 2-10. Claim 42 is drawn to Claim 41 and recites co-administering the pharmaceutical composition with an additional medicament wherein the additional medicament is selected from an antibacterial agent, an antifungal agent, an antiviral agent, an anti-inflammatory agent, or an antiallergic agent. Claim 43 is drawn to Claim 41 and recites wherein the additional medicament is a b-lactam antibacterial agent, and wherein the b-lactam antibacterial agent is selected from Ceftazidime, Biapenem, Doripenem, Ertapenem, Imipenem, Meropenem, Panipenem, Aztreonam, Tigemonam, BAL30072, SYN 2416, or Carumonam.
47. Thus, the genus of compounds recited in U.S. 10,206,937 B2 of Formula (I-I) fully embraces and only differs from Applicant’s instant genus of Formula (Ic) as positional isomers, i.e. the “Y-(CR8R9)n-G” substituent is in the ortho position relative to the -OH moiety , wherein Applicant’s “-CH2-G” substituent is in the meta position relative to the -OH moiety. The genus of compounds recited in U.S 10,206,937 B2 of Formula (I-2) fully embraces the genus that is instantly recited by Applicant in Formula (IIc) but differs in the placement of the “G” substituent on the ethyl group, i.e., the “Y-(CR8R9)n-G” substituent is in the “2” position relative to the ring , wherein Applicant’s “-CH2-G” substituent is in the “1” position relative to the ring.
48. Yet, compounds that are position isomers (compounds having the same radicals in physically different positions on the same nucleus) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious).
49. Therefore one skilled in the art would be motivated to treat the instantly recited bacterial infections comprising administering an instant compound of Formula (Ic) or Formula (IIc), which are positional isomers of the known boronic acid derivatives previously recited in U.S. 10,206,937 B2, and would have had reasonable expectation of success that the similar compounds would have similar pharmacokinetic properties, oral availability, antimicrobial potency, and/or duration of effect, etc.
50. And, "[a]n obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) (discussed in more detail below) and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990). See MPEP § 2144 for an extensive review of the case law pertaining to obviousness based on close structural similarity of chemical compounds.
51. Regarding the comprehensive of the genus recited, a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989). See also Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005)(reference disclosing optional inclusion of a particular component teaches compositions that both do and do not contain that component); Celeritas Technologies Ltd. v. Rockwell International Corp., 150 F.3d 1354, 1361, 47 USPQ2d 1516, 1522-23 (Fed. Cir. 1998) (The court held that the prior art anticipated the claims even though it taught away from the claimed invention. "The fact that a modem with a single carrier data signal is shown to be less than optimal does not vitiate the fact that it is disclosed."). Furthermore, "[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).
52. Claim 42 of U.S. 10,206,937 B2 recites the same group of additional medicaments that are recited by Applicant in instant claim 12. And, the subgenus of additional medicaments (specifically b-lactam antibacterial agents) recited by Applicant in instant claims 15 and 16 are embraced by the genus recited in claim 43 of U.S. 10,206,937 B2.
53. Thus, one skilled in the art would have been motivated to treat a bacterial infection in a subject in need thereof comprising administering a compound of Formula (I) or Formula (II), which are positional isomers of the known genus of previously patented boronic acid derivatives of U.S. 10,206,937 B2, and would have had a reasonable expectation of success.
As such, claims 1-20 are prima facie obvious over Claims 41-43 of U.S. 10,206,937 B2.
Response to Arguments
54. Applicant traverses the previous double patenting rejection of claims 2-20 over the claims of U.S. Patent No. 9,132,140, and over the claims of U.S. Patent No. 9,241,947, and over the claims of U.S. Patent No. 10,206,937. Applicant argues that one skilled in the art, based on the claims of U.S. Patent No. 9,132,140, U.S. Patent No. 9,241,947, or U.S. Patent No. 10,206,937, would not have had a reasonable expectation that moving a hydroxyethyl substituent from the position alpha to the boron atom to the beta position would result in a compound that would have any biological activity, let alone antimicrobial activity. Applicant contends that despite this lack of expectation, the claimed compounds bearing a substituent at the beta position have an improved beta lactamase inhibitor profile in comparison with the alpha compound disclosed by Reddy. 55. Applicant references the declarations submitted under § 1.132 by Dr. Scott Hecker ("Hecker Declaration I" dated September 26, 2022, and "Hecker Declaration II" dated March 23, 2023) in parent Application No. 17/048,052. Hecker Declaration I compares the compound in Reddy with Compound 12 in the instant application, wherein the data show that, of the 26 different strain/antibiotic combinations tested, Applicant’s Compound 12 exhibited a higher activity than the compound disclosed in Reddy in ten of the strain/antibiotic combinations. Applicant alleges that the instantly claimed compounds have a surprisingly improved overall profile compared to the alpha isomer for treating a patient having a bacterial infection.
55. Hecker Declaration II compares the Reddy compound with several additional instantly claimed compounds (Compounds 1, 3-8, and 11), wherein the results show that these compounds are also superior to the Reddy compound. Applicant alleges that of the 14 different strain/antibiotic combinations tested, each of the instantly claimed compounds exhibited a higher activity than the Reddy compound in at least 12 of the strain/antibiotic combinations. Furthermore, instant Compounds 3-8 and 11 exhibited higher activity in all 14 strain/antibiotic combinations.
In addition, compounds from the present application were compared with a compound ("Compound A"), which differs from Compounds 1, 3-8, and 11 only in the position of the hydroxymethyl or methoxymethyl substituent on the benzoxaborinine ring. This comparison showed that of the 14 different strain/antibiotic combinations tested, each of the compounds from the present application exhibited a higher activity than Compound A in at least 12 of the-10-strain/antibiotic combinations, and that Compounds 3-8 and 11 exhibited higher activity in all 14 strain/antibiotic combinations.
Applicant argues that the results demonstrate that the unexpectedly improved properties compared to the compound in Reddy (and compared to the compounds claimed in U.S. Patent No. 9,132,140, U.S. Patent No. 9,241,947, or U.S. Patent No. 10,206,937) can be generalized to other compounds of the present application that are substituted at the position beta to the boron atom.
56. Applicant's arguments have been fully considered but they are not persuasive. It is well settled that a showing of unexpected results is generally sufficient to overcome a prima facie case of obviousness. In re Albrecht, 514 F.2d 1389 (CCPA 1975). In the instant case, Applicant has appropriately compared compound 12 of the claimed invention with that of the closest prior art (the compound in Reddy et al.) in Hecker Declaration I, and has appropriately compared compounds 1, 3-8 and 11 of the claimed invention with that of the closest prior art (the compound in Reddy et al.) in Hecker Declaration II, and provided factual evidence which establishes unexpected results of the claimed invention. However, although the evidence establishes unexpected results, Applicant is reminded that “the objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support” (In re Clemens, 622 F.2d 1029 (CCPA 1980)). Thus, in In re Peterson, 315 F.3d 1325 (Fed. Cir. 2003), factual evidence demonstrating a greater than expected result from the addition of 2% of an ingredient did not evidence unexpected results for the entire claimed range of about 1-3% of the ingredient. Rather, the nonobviousness of a broader range or genus can only be established by evidence based on unexpected results of a narrower range or genus when one of ordinary skill in the art would be able to determine a trend in the exemplified data allowing said artisan to reasonably extend the probative value thereof. In re Kollman, 595 F.2d 48 (CCPA 1979).
In the instant case, the claims are not drafted commensurate in scope with the unexpected results to overcome the prima facie case of obviousness, because Hecker Declarations I and II compare the activity of Applicant’s instantly claimed compounds 1, 3-8, 11 and 12 with the position isomer taught by Reddy et al. and with Compound A. However, neither of the Hecker Declarations compare the activity of any compounds according to instant Formula (IIc) with their corresponding position isomers recited in U.S. Patent No. 9,132,140, U.S. Patent No. 9,241,947, or U.S. Patent No. 10,206,937.
Accordingly, the double patenting rejections are maintained.
Conclusion
57. Claims 2-20 are present in the application. Claims 2-20 are rejected. No claim is presently allowable.
58. 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.
59. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JANET L COPPINS whose telephone number is (571)272-0680. The examiner can normally be reached Monday-Friday 8:30AM-5PM EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy Clark can be reached on 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JANET L COPPINS/Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628
Prosecution Insights