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 and Claims Status
Claims 39-51 were pending. In the amendment as filed on 7/29/2025, applicants have amended claims 39, 45, and 49-50; cancelled claims 43; and added no new claims. Therefore, claims 39-42, and 44-51 are currently pending.
Response to Amendment
The amendments received 07/29/2025 have been entered. Claims 39-42, and 44-51 are pending. Applicant is notified that any outstanding rejection/objection as set forth in the Office Action mailed 04/2/2025 that is not expressly maintained herein has been withdrawn or rendered moot in view of applicant's amendments and/or remarks.
Specification
Applicant is reminded of the proper content of an abstract of the disclosure.
In chemical patent abstracts for compounds or compositions, the general nature of the compound or composition should be given as well as its use, e.g., “The compounds are of the class of alkyl benzene sulfonyl ureas, useful as oral anti-diabetics.” Exemplification of a species could be illustrative of members of the class. For processes, the type of reaction, reagents and process conditions should be stated, generally illustrated by a single example unless variations are necessary.
The abstract of the disclosure is objected to because: the general nature of the compound or composition is not provided. Exemplification of a species or genus would be sufficient to provide the general nature of the compound or composition. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
The specification is objected to because of the following minor informality: in the structure of compound 2, page 128, the -NH2 group is misaligned. Appropriate correction is required.
Claim Objections
Claim 39 and 42 are objected to because of the following informalities: the chemical structures have not been drawn by a process that gives them satisfactory reproduction characteristics, as the R variables are not clearly drawn. Every line, number, and letter must be durable, clean, black, sufficiently dense and dark, and uniformly thick and well-defined. In the limitation of R12, the term “C1-4alky-NR14R15” is missing the ‘l’ in alkyl, and should be rewritten as “C1-4alkyl-NR14R15”. In the limitation of R10, the claim currently reads “R10 is pyridyl is optionally substituted…” (emphasis added) and should read “R10 is pyridyl optionally substituted…”. In the limitation of R10, the dash in front of “-CF3” is unusually long and should appropriately be a dash and not an em dash. Additionally, claim 42 is objected to for the following informality: in the limitations of R11 and R10, a quaternary ammonium cation, “(NR16 4 +)” should be rewritten without extra spaces as “(NR164+)”. Appropriate correction is required.
Claim 44 is objected to because of the following informality: the claim ends with two periods, when there should only be one period. Appropriate correction is required.
Claim 48 is objected to because of the following informality: the linking conjunction “and” at the end of the claim should not be italicized. Appropriate correction is required.
Claim 49 is objected to because of the following informality: Applicant writes “…about 0.01 micrograms per kilogram body weight (mg/kg)”. Examiner notes that the units “(mg/kg)” is currently milligrams per kilogram despite the previous claim language specifying micrograms per kilogram, which would accurately be written as “(µg/kg)”. Appropriate correction is required.
Claim 51 is objected to because of the following informalities: the term “Enterobacteriaceae” should be italicized. Claim 51 is objected to for lack of clarity. For sake of clarity and consistency, claim 51 should read, “A method of treating a bacterial disease or a bacterial infection caused by Enterobacteriaceae in a subject in need thereof, comprising administering to said subject an effective amount of a composition comprising a compound of claim 39.” Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 39-42, and 44-51 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 39-42, and 44-51 are rejected as vague. Claims 39 and 42 recite, in the limitation of R12 and R10, “…and a quaternary ammonium cation (NR164+)”. Currently, the positive charge is on the R16 group, forming carbocations, while the claim limitation is attempting to claim ammonium ions.
Claim 39 is rejected as vague. The current claim recites “a method of treating a bacterial disease or bacterial infection comprising administering to a subject in need thereof a compound…having the general formula (V)” (emphasis added). Is Applicant administering any amount of compound (which could be suboptimal and have no therapeutic benefit), or a therapeutically effective amount? Examiner recommends adding a “therapeutically effective amount” into the claim language.
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Claim 48 is rejected as vague. The claim is drawn to the method of claim 39, wherein the infection is “caused by Enterobacteriaceae genera selected from the group consisting of…” and the remainder of the claim recites selections from the group Enterobacteriaceae genera. Enterobacteriaceae genera belongs to the taxonomical hierarchy of family of bacteria, but the “selections from the group consisting of” go on to list groups that do not belong under the family of Enterobacteriaceae genera. For instance, Arsenophonus belongs under the family Morganellaceae, Brenneria belongs to the family of Pectobacteriaceae, Buchnera belongs to the family of Erwiniaceae, etc.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 40 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 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. Claim 39 only specifies that R2 is NH2, which is the same definition of R2 in independent claim 40. 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.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Scope of Enablement
Claims 39-42, and 44-51 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 the treatment of bacterial diseases or infections caused by Gram-negative bacteria, does not reasonably provide enablement for the treatment and prevention of all bacterial diseases or infections. 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.
Such a utility cannot be deemed enabled. Pursuant to In re Wands, 858 F.2d 731,737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. Some experimentation is not fatal; the issue is whether the amount of experimentation is "undue"; see In re Vaeck, 20 USPQ2d 1438, 1444. The analysis is as follows:
Breadth of claims:
Scope of the compounds. The instant claims are drawn to a method of treating using a compound of formula (V), which encompasses thousands of compounds with an imidazole core..
Scope of the diseases covered. The instant claims are drawn to a method of treating a bacterial disease or infection caused by any bacteria. The treatment of any bacterial infection generally cannot possibly be considered enabled. The source of bacterial infection is diverse and there is a large number of bacterial infections. Bacteria are single-celled microorganisms known as prokaryotes. There are estimated to be at least one nonillion bacteria on Earth. A nonillion is a one followed by 30 zeros. Much of Earth's biomass is made up of bacteria. Bacteria take three main shapes:
Spherical: These are usually the simplest to treat and are known as cocci.
Rod-shaped: These are called bacilli.
Spiral: Coiled bacteria are known as spirilla. If the coil of a spirillus is particularly tight, they are known as spirochetes.
Bacteria can live in almost any kind of environment, from extreme heat to intense cold, and some can even survive in radioactive waste. There are trillions of strains of bacteria, and few of these cause diseases in humans. Some of them live inside the human body without causing harm, for example in the gut or airways. Some "good" bacteria attack "bad" bacteria and prevent them from causing sickness. However, some bacterial diseases are deadly. These include: cholera, diphtheria, dysentery, bubonic plague, pneumonia, tuberculosis, typhoid, typhus, etc. Some examples of bacterial infections are: bacterial meningitis, otitis media, pneumonia, tuberculosis, upper respiratory tract infection, gastritis, food poisoning, eye infections, sinusitis, urinary tract infections, skin infections, sexually transmitted diseases, etc. Bacterial infections can be treated with antibiotics, but some strains become resistant and can survive the treatment.
(B) The nature of the invention and predictability in the art:
The invention is directed toward a method of treating a bacterial disease or infection using a compound of formula (V). It is well established that "the scope of enablement varies inversely with the degree of unpredictability of the factors involved," and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
(C) Direction or guidance:
The guidance provided is very limited. The dosage range information is not found in the Specification. Thus, there is no specific direction or guidance regarding a regimen or dosage effective specifically for a method of treatment for a Gram-negative bacterial infection, let alone bacterial infections, in general.
Applicant does provide, in Example A on pages 175-180, MIC values for the instantly claimed compounds against various Gram-negative bacterial strains. Applicant does not, however, provide MIC values for the instantly claimed compounds against Gram-positive bacterial strains.
(D) State of the prior art:
The method of treating involves administering a compound of Formula (V) for the treatment of bacterial infections or bacterial diseases. So far as the examiner is aware, there is no universal drug for the treatment of all bacteria.
The term “treatment” is defined on pages 15-16 of the specification and said definition also embraces prevention.
It is presumed “prevention” of the claimed condition would require a method of identifying those individuals who will develop the claimed condition before they exhibit symptoms. The current state of the art is that that full scope of diseases claimed within instant claims is not preventable or curable.
There is no evidence in the prior art that the instant composition would be usable as a preventative method, particularly for preventing bacterial diseases or bacterial infections. “Preventing” connotes an absolute absence of a condition which cannot reasonably be achieved with regard to infections, with few exceptions (such as vaccines to prevent the development of pathogen-borne illnesses). In addition, there is no definitive method by which to determine whether a patient will develop a particular condition and, thus, be in need of preventive therapy. This is distinguished from preventing the relapse or recurrence of certain conditions, in which case an objective basis may exist to identify patients at risk of disease or infection, and could reasonably be construed as treatment. Prior to the initial onset or occurrence, however, even if a patient can be identified as having known risk factors for a condition, there is no certainty that the patient would in fact develop the condition. Further, the failure of a disease, infection, or condition to develop cannot reliably be attributed to the claimed active agent(s). The non-development of a condition such as bacterial diseases or bacterial infections may be due to other factors such as lifestyle. In this sense, in the context of preventing a disease, the level of unpredictability is extremely high.
(E) Working examples:
The invention is drawn to a method of treating bacterial diseases or bacterial infections, generally. There are eighteen bacterial strains used in these studies and they are found in the Specification on pages 177-180 (Table 1). Included in Table 1 is Staphylococcus aureus (SA), which is a Gram-positive bacteria. None of the instantly claimed compounds are able to inhibit SA, and have a value of D, indicating an MIC over 100 µM.
(F) Skill of those in the art:
Antibiotics are usually effective against either Gram-positive or Gram-negative bacteria. There are very few that have been able to treat both types of bacteria. These "super drugs" are usually kept for resistant strains because they are so valuable and hard to come by. Furthermore, there are no methods of compositions that can treat all infections (bacterial, viral, fungal) generally.
(G) The quantity of experimentation needed:
Owing especially to factors A, C, E and F, the amount of experimentation is expected to be high. MPEP 2164.01(a) states, "A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)." That conclusion is clearly justified here.
Claim Rejections - 35 USC § 103
The rejection of claims 39-42 and 44-51 under AIA 35 U.S.C. 103(a) as being unpatentable over Mcleod et al. (J. Bacteriol., January 12, 2015) is withdrawn based on the amendments.
The rejection of claims 39-42 and 44-51 under AIA 35 U.S.C. 103(a) as being unpatentable over Mcleod et al. (J. Bacteriol., January 12, 2015) in view of Richter et al. (Chem, Cell Press, July 13, 2017) is withdrawn based on the Applicant’s arguments.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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.
Claims 46-51 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 6, 9, 11-13, 16, 21, 22, of copending Application No. 18/588,163 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Reference claim 2 is drawn to a method of treating an infection or disease caused or exacerbated by Gram-negative bacteria of the order Enterobacterales, comprising administering to a subject an effective amount of compound (I). Compound (I) is a species that reads on the genus on instant claim 39, where instant R12 is COR13, R13 is C1alkyl, optionally substituted with one or more substituents selected from the group of C1alkyl and NR3R4, where R3 and R4 are methyl. Further, instant claim 46 is drawn to a method of treating an infection or disease caused by Enterobacteriaceae using a compound of instant claim 39.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 39-42 and 44-51 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11,345,694 (cited on IDS filed 12/20/2022). Although the claims at issue are not identical, they are not patentably distinct from each other because the methods of treating bacterial diseases or infections of instant independent claims 39 overlap in claimed matter with at least claim 1-10 of the issued U.S. patent.
In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014), the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See also Pfizer, Inc. v. Teva Pharm. USA, Inc., 518 F.3d 1353, 86 USPQ2d 1001 (Fed. Cir. 2008);Geneva Pharmaceuticals Inc. v. GlaxoSmithKline PLC, 349 F3d 1373, 1385-86, 68 USPQ2d 1865, 1875 (Fed. Cir. 2003).
Here, the same compounds of Formula (V) are recited in both the instant application and the patent. Although the issued patent does not claim a method of use, the disclosure of the patent (Abstract; col 1, lines 6-12, 17-59) recites “the present invention relates to compounds of general Formula (II), to compositions comprising these compounds and to method of treating Enterobacteriaceae bacterial diseases and infections using the compounds. The compounds find application in the treatment of infection with, and diseases caused by, Enterobacteriaceae.”
The ordinary artisan would recognize as obvious that determination of whether “a method of treating a bacterial disease or bacterial infection” using a compound of formula (V) is present in the instant claims, is implicit in the patented claim in view of Sun Pharmaceutical Industries, LTD. v. Eli Lilly and Company which states the following: “Similarly, in Pfizer, the earlier patent claimed several compounds and the specification disclosed their use in treating inflammation and inflammation-associated disorders. 518 F.3d at 1363 & n.9; see 5,563,165 (“’165 patent”), at [57], col.1 11.11-14, col.3 11.3-27. The later patent then claimed a method of using these compounds for treating inflammation, inflammation-associated disorders, and specific inflammation-associated disorders, including arthritis, pain, and fever. Pfizer, 518 F.3d at 1363 & n.9; see U.S. Patent No. 5,760,068 (“’068 patent”) col.97 1.49- col. 108 1.29. After rejecting the patentee’s objection to our consideration of the specification of the earlier patent, we determined that the later patent “merely claims a particular use described in the [earlier] patent of the claimed compositions of the [earlier] patent.” Pfizer, 518 F.3d at 1363 & n.8. As such, we concluded that the asserted claims of the later patent were not “patentably distinct” from the claims of the earlier patent, and thus the later patent was invalid for obviousness-type double patenting. Id. at 1368.
Closest Prior Art
The prior art made of record and not relied upon that is considered closest art to Applicant’s disclosure is found in:
Kim et al. (“Synthesis and Biological Evaluation of 4(5)-(6-Alkylpyridin-2-yl)imidazoles as Transforming Growth Factor-β Type 1 Receptor Kinase Inhibitors”, published June 7, 2007)(hereinafter, ‘Kim’).
The compound disclosed by Kim, Compound 16 in Scheme 2, on page 3144, only contains one methylene unit in the R7 heterocyclic ring, not two or three methylene units. Furthermore, Kim does not disclose their use as a treatment for bacterial infections or diseases.
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Dodic et al. (WO 2004/111046 A2, published December 23, 2004)(hereinafter, ‘Dodic’).
The compound disclosed by Dodic, Example 8 on page 32, contains a thiazole ring, not an imidazole ring.
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Furthermore, Dodic does not disclose their use as a treatment for bacterial infections or diseases.
Conclusion
No claims are allowed.
All claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LUKE ALAN BORALSKY whose telephone number is (571)272-9746. The examiner can normally be reached Monday - Friday 7:30 am - 5:00 am.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey H Murray can be reached at 571-272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/L.A.B./Examiner, Art Unit 1624
/SUSANNA MOORE/Primary Examiner, Art Unit 1624
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