DETAILED ACTION
Formal Matters
Claim 1-20 are pending.
Claims 5, 7, 10, 12, and 14 are withdrawn as reading on non-elected species.
Claims 1-4, 6, 8-9, 11, 13 and 15-20 are under examination.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application is a CIP of 17/157,118 filed on 1/25/2021, which is a divisional of 15/887,469 filed on 2/2/2018, which claims priority from US provisional applications 62/524,866 filed on 06/26/2017, 62/483,032 filed on 04/07/2017 and 62/453,701 filed on 2/2/2017.
Description Issue in Priority Documents
The following continuation-in-part (CIP) application supports the items of its claims as of its filing on 9/28/2023, however, not all the subject matter is supported by the priority documents filed prior to this date. The range endpoints supported for bicarbonate included from 0 to 200 mM via figures including figures 24 and 25 as well as values listed in the disclosure of priority documents within this range (15/887,469 filed on 2/2/2018). Applicant also has broader support in priority documents for any amounts and effective amounts of bicarbonate, but not for other specific values over 200 mM, for 1.75 wt% or for 8.4 wt%. There is no priority document support for endpoints such as 900 mM, 1.75wt% and 8.4 wt% in priority documents prior to the CIP filing. This is also an issue for the subgenre of semi-synthetic or synthetic antibiotics and semi-synthetic and synthetic compounds found in applicant’s claims. Thus, for claims with these claimed ranges and agents containing matter only supported by the filing on 9/28/2023, they will be examined considering the filing date of 9/28/2023. A further explanation is offered in the rejection under USC 102 over intervening prior art below.
Information Disclosure Statements
The IDS from 10/20/2023, 11/15/2023, 11/16/2023 and 9/27/2024 have been considered by the examiner.
Election/Restrictions
Applicant’s election without traverse of species A) azithromycin and B) Staphylococcus in the reply filed on 2/23/2026 is noted by the examiner. Claims 1-4, 6, 8-9, 11, 13 and 15-20 read on the elected species. The election is treated as without traverse as the applicant does not make a traversal regarding the election requirement.
Claims 5, 7, 10, 12, and 14 are withdrawn without traverse as reading on non-elected species.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-4, 6, 13, and 15-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to natural products without significantly more. The claim(s) recite(s) antibiotics and bicarbonate where macrolide antibiotics include a number of natural compounds including erythromycin and spiramycin (natural macrolides). Natural antibiotics can also include many other naturally occurring compounds of various forms that can kill bacteria as part of an organisms defense mechanism. In regards to non-physiological concentration/amount, this term is unclear to what physiology it applies to, but it may refer to “about 25 mM” which is the physiological concentration of bicarbonate in human blood. Thus, any other concentration above or below “about 25 mM” would constitute non-physiological concentrations for the claim. Pharmaceutical carriers, diluents and excipients include natural compounds like water, sugars, salts and various other natural compounds. Bicarbonate salts exist in nature. There are natural buffering systems in cells that include bicarbonate in microbes, animals and plants where amounts vary based on natural substance being buffered or conditions of the subject. The composition of the claims do not have to have a specialized, non-natural form that would have markedly different characteristics from the natural compounds. The claims do not indicate whether the bicarbonate and antibiotic is present in a manner that provides significantly more than the activities provided in nature (e.g. natural buffering and pH adjusting abilities of bicarbonate and natural antibiotic activity of naturally occurring macrolide or antibiotic compounds, natural antibacterial actions of bicarbonate). In regards to contacting bacteria with bacterium, as bicarbonate and natural antibiotic compounds exist naturally in proximity in natural systems, the ability of antibiotics or bicarbonate to inhibit bacterial growth is inherent to the antibiotic compound and/or bicarbonate on their own as these compounds are present in organisms and environments where bacteria would be present since bacteria are ubiquitous. Farha et al (ACS Infectious Diseases, 2018, volume 4, pages 382-390) teaches that antimicrobial properties of sodium bicarbonate have been known for years and that “bicarbonate is a selective dissipater of the pH gradient of the proton motive force across the cytoplasmic membrane of both Gram-negative and Gram-positive bacteria” (abstract of Farha). Farha also teaches “Although the immune response and the buffering system have distinct functions in the body, we posit there is interplay between these, as the antimicrobial properties of several components of innate immunity were enhanced by a physiological concentration of bicarbonate” (abstract of Farha and pages 382-383, also figure 4 and page 387). Thus, the interactions of bicarbonate with natural antibiotic compounds naturally have these capabilities for natural immunity against bacteria that can invade an organism. Even as claims 1 and 17 provide for non-physiological concentrations of bicarbonate, this does not clearly dictate in what sense physiological is (in blood, in plants, in microbial cells) or provide for a particular concentration. The main interaction is between the bicarbonate and natural antibiotic which may be one that occurs in nature and in varying amounts. In regards to kit, this just amounts to packaging/containing compounds of nature, which does not change the structure of the products of nature. Claim 17 provides for first bicarbonate composition and second antibiotic composition with an option of either the first composition comprising a non-physiological concentration of bicarbonate; or the second composition comprises a synthetic or semi-synthetic comprises a synthetic or semi-synthetic compound (does not indicate the compound has to be the antibiotic). Even if the option with semi-synthetic or synthetic compound is chosen, as this may be any compound including those that are inert excipients, this would not change the structure of the potentially natural antibiotic or the bicarbonate which is in the separate first composition. Different administered forms amounts to compositions being separated where bicarbonate and other agents can be compartmentalized in cells or bodies. In claim 13, a composition of claim 1 may be used. Therefore, the claimed compositions and kit provide for naturally occurring compounds without markedly different characteristics and the method occurs naturally where natural bicarbonate and natural antibiotics are present in natural organisms as natural bacterial defense mechanisms. Since bicarbonate and natural antibiotic compounds are known to interact naturally for the effect of being antibacterial, the effect provided by the natural combination and contact with bacterium also occurs naturally.
Claim Rejections - 35 USC § 112(a) – Scope of Enablement (Synthetic/Semi-synthetic and Analogs)
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.
Claims 6, 8, 9, 11, 13, and 15-20 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 particular subgenre (macrolide, aminoglycoside, polymyxin, tetracycline, cephalosporin, quinolone, fluoroquinolone) and species of compounds (e.g. amikacin, azithromycin, oxacillin) noted in claim 3 or species in claim 6, where some might happen to be synthetic and some are semi-synthetic, does not reasonably provide enablement for all such synthetic or semisynthetic compounds/antibiotics or analogs of such compounds (see claims 6, 8, 17, for example). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims. Semi-synthetic or synthetic antibiotics or compounds seek to define the antibiotics or compounds by some type of semi-synthetic or synthetic mechanism by which they are made. “Analogs” seeks to provide additional compounds that are analogs of the ones listed, but the specification or claim does not provide what would constitute an analog other than providing few example species for some compounds.
Breadth of the Claims
The claims encompass a broad genus of synthetic and semi-synthetic antibiotics or compounds as well as analogs of some compounds, but does not provide a meaningful structural limitation to what would constitute such compounds (i.e. what structure or structures are provided by synthetic, semi-synthetic or analog in regards to an antibiotic or compound). As synthetic, semi-synthetic or analog can provide a vast number of compounds of various structures and functions (e.g. different addition groups, various types of isomerism, inclusion in polymers, biosteres, etc.) with each having potentially different and not-yet-known activities, the enablement is not commensurate in scope with the relatively fewer number of compound species or classes/subgenre that are provided and have these functions.
The chemical and pharmaceutical arts are unpredictable in regards to structure-function relationships.
The prior art might provide methods for synthesizing species or classes of antibiotics or compounds as well as for synthesizing particular analogs of antibiotics, but it does not provide for all the ways of synthesizing or modifying the broad and diverse compounds that would be covered by these recitations. Stojkovic et al (Antibiotics, 2023, volume 12, pages 1-25) is a review on making new synthetic and semi-synthetic antibacterials that target virulence factors (abstract). Stojkovic teaches there are several challenges in making such synthetic or semi-synthetic compounds for combatting antibacterial resistance (section 9 of Stojkovic). Challenges include identification of new compounds that have antibacterial action and targeting virulence factors and also optimizing the efficacy and safety (section 9). Stojkovic also recognizes a need to understand the mechanisms of such compounds. Stojkovic teaches “However, given the complexity
of bacterial pathogenesis and the evolution of resistance mechanisms, the development
of novel antibacterials remains a challenging task.” (section 10 conclusions). Thus, the art recognizes making new compounds for antibiotic effects has challenges related to both identifying the new compounds and optimizing their efficacy and safety. The art also recognizes a complexity in bacterial pathogenesis which also makes this a challenge.
A person of skill in the art would be an organic chemist or pharmacologist.
The antibiotic art is highly unpredictable in regards to efficacy, stability and toxicity of compounds. Enablement would involve not just changing synthetic or modification processes, but also testing to ensure desired efficacy, toxicological profiles or other features. Even seemingly small structural changes can lead to big differences.
Applicant does not provide synthetic pathways for diverse scaffolds, conditions required for modifications and all the structure-activity relationships that would be offered under these broad terms. Applicant provides species, classes or subgenre that are known to work, but does not provide a roadmap on how to make all of the compounds that would be covered by these claims reciting terms such as synthetic, semi-synthetic and analog. For example, a synthetic or semi-synthetic antibiotic or macrolide antibiotic, although being different from a natural antibiotic or natural macrolide antibiotic does not provide for structures or the structure-function relationship for each of the compounds provided by new synthetic processes. Mention of an analog also does not provide the type of analog structure and its structure-function relationship.
Applicant does not provide synthetic procedures to make various antibiotics and testing thereof or making and testing a diverse type of analogs of listed compounds that would offer enablement for these recitations. Applicant does provide for species of particular antibiotics as well as classes, where those would be enabled by the art. However, note that terms like synthetic, semi-synthetic and analog imply some type of modification or addition to structure without actually dictating that structure which also does not allow one to determine all the structural/functional relationships that might result.
As one of skill in the art would need to make and test each compound that can be considered a synthetic, semisynthetic or analog version of an antibiotic or compound, there would be a large amount of experimentation required to develop the new processes as well as testing to ensure efficacy and desired properties of the many diverse compounds that could be produced under these recitations. Thus, there would be undue experimentation on one of skill in the art to make and use synthetic antibiotics, semi-synthetic antibiotics or analogs of any of the listed compounds or classes.
Conclusion:
Although applicant is enabled for species of compounds and classes of antibiotics listed (e.g. azithromycin, macrolide antibiotics), applicant is not enabled for all synthetic, semi-synthetic or analogs as there is not enough information provided in the art or the specification to allow one of skill in the art to make and test the numerous, diverse compounds that could be made by numerous, different processes of synthesis/modification. Applicant may remove recitations of synthetic, semi-synthetic and analogs from the claims. Applicant may instead use Markush groups of species of compounds in the specification (e.g. azithromycin) that are known to be synthetic, semi-synthetic or analogs.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 3-4 , 6, 8, 9, 11, 13, 15-20 are 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 pre-AIA the applicant regards as the invention.
Claims 1 and 17 are vague and indefinite for the recitation of “non-physiological concentration of the bicarbonate” as “physiological” can refer to a number of various organisms each having different physiological levels of bicarbonate. Thus, it is unclear what amount “non-physiological concentration” is referring to in the claim as physiological amounts can vary significantly. The specification in paragraph 144 indicates that in some embodiments, the dosage or amount of the bicarbonate provides a non-physiological concentration of bicarbonate, for example, the bicarbonate dosage or amount is greater than 25 mM, e.g. greater than 25 mM, about greater than 30 mM of bicarbonate, which is merely exemplary of what applicant might consider non-physiological without providing for a particular amount or defining what non-physiological refers to specifically. The definitions of the specification do not define non-physiological. For the purpose of compact prosecution, prior art teachings of an amount of bicarbonate that is not 25 mM will be considered as “non-physiological concentrations”. Applicant may amend the claim to put in particular ranges as supported by the originally filed application and/or priority documents.
Claims 3-4 , 6, 19 and 20 are rejected as being dependent on an indefinite claim without fixing the issue.
Claims 8 and 17 are indefinite for the recitations of synthetic or semi-synthetic in regards to antibiotic or compound as they do not provide for a particular structure or structures provided to the antibiotic or compound, but rather claim by generic use of “synthetic” or “semi-synthetic”. Since there may be numerous, diverse ways to synthesize antibiotic or compounds with different groups or modifications, it is unclear what the metes and bounds of synthetic or semi-synthetic will provide to the claims. For the purpose of compact prosecution, if the examiner finds an antibiotic (claim 8) or compound (claim 17) that is considered synthetic or semi-synthetic then it will read on the limitation.
Claims 9, 13, 15-16, and 18-20 are rejected as being dependent on indefinite claims without correcting the issue of indefiniteness.
Claims 6 and 11 are indefinite for the recitation of “analogs” thereof in these claims with different macrolide antibiotic species. The specification does not provide a particular definition to analog nor provide a basis for what structure analog will be considered for when considering the limitation. Analogs may cover a large variety of different compounds based on the before mentioned compounds with different structures and functional consequence based on numerous changes/modifications that might be made to such compounds. Therefore, it is unclear what metes and bounds “analog thereof” provides to these claims. For the purpose of compact prosecution, if the prior art provided a compound that would be a possible analog (functional and/or structural) of one of the listed compounds, it will read on applicant’s claim.
Claim 20 is indefinite as the claim provides the antibiotic composition comprises an aminoglycoside, a polymyxin, or a macrolide where claim 17, on which it depends, provides the second composition (antibiotic composition) comprises a synthetic or semi-synthetic compound where the compound is not necessarily provided to be the antibiotic portion of this composition. Thus, it is unclear if applicant means claim 20 to limit the “synthetic or semi-synthetic compound” or if this is meant to be an additional agent present in the second antibiotic composition. For the purpose of compact prosecution, the examiner will consider claim 20 as an additional component in the second composition.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 2, 8-9, 11, 13, and 15-20 and in part claim 1 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Brown US 20210145854A1 (published more than one year from supported filing date of 9/28/2023).
Claims 2 and 8 contain ranges that extend to a determined endpoint of 900 mM that is not provided by the priority documents. Priority documents only provide for a maximum of 200 mM as an endpoint by way of figures 24 and 25. Therefore, the consideration of the range from above 200 mM to 900 mM bicarbonate which was added in this CIP application is considered with the filing date of the CIP, which is 9/28/2023.
Claim 18 provides for “about 1.75 wt% to about 8.4 wt%” for bicarbonate, which would translate to about 208 mM to about 1000 mM bicarbonate. Again, the maximum supported endpoint is 200 mM for bicarbonate in priority documents. Note that a genus does not necessarily give description for a subgenus or species. See MPEP 2163 (II, A, 3, (a) and (b)).
In addition, there is no mention of antibiotic as being in the subgenre of semi-synthetic or synthetic or compounds as being synthetic or semi-synthetic in regards to claims 8 and 17. Although azithromycin or dirithromycin may be species within semi-synthetic antibiotics/compounds and ciprofloxacin and besifloxacin may be species of synthetic antibiotics/compounds, they do not give full description in priority documents for such subgenre, which can include many, diverse compounds. Note that naming some species does not give ownership over a genus unless the listed species are representative of the entire genus.
Therefore, claims 2, 8 and 18 with their dependent claims will be considered for prior art as containing ranges with a new endpoint that was not disclosed in previous priority documents.
Brown teaches compositions with bicarbonate and antimicrobial agent (abstract) and teaches “the bicarbonate is present in a composition (a) at a concentration of about 1 millimoles/L to about 900 millimoles/L of the composition; or (b) in an amount of about 0.01 wt % to about 8.4 wt % of the composition; and the antimicrobial agent is present in a composition” (paragraphs 8-12). Brown teaches azithromycin with bicarbonate (paragraph 403). Brown teaches “In some embodiments, the composition comprises bicarbonate at a concentration of about 175 mM to about 225 mM, about 200 mM to about 300 mM, about 300 mM to about 400 mM, about 400 mM to about 500 mM, about 500 mM to about 600 mM, about 600 mM to about 700 mM, about 700 mM to about 800 mM or about 800 mM to about 900 mM.” (paragraph 175). Table 1 and example 5 teaches staphylococcus aureus as does figure 6A (also see paragraph 343). Paragraphs 343-344 notes the antibacterial activity of sodium bicarbonate on Staphylococcus aureus. Paragraph 392 provides for azithromycin and bicarbonate treating Staphylococcus aureus. Brown teaches quinolones and fluoroquinolones (paragraphs 116-117 and table 3) as well as other macrolides like dirithromcyin (table 3 and example 8) as compounds that can be combined with bicarbonate in its disclosure.
Therefore, Brown teaches the limitations of applicant’s claims including concentrations of bicarbonate from above 200 mM to 900 mM, 300 mM to 400 mM, 800mM to 900 mM and others; and other particular antibiotic compounds that would be semi-synthetic or synthetic. With this said applicant, may regain support of the necessary priority documents to overcome this rejection by amending the claims to remove limitations (endpoints or subgenus terms) not supported by the priority documents while including limitations supported by the priority documents instead.
Claim(s) 1-4, 13, 16-17, 19 and 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gutierrez-Huante et al (Letters in Applied Microbiology, 2015, volume 60, pages 440-446, in applicant IDS).
The following prior art is applied as it anticipates many of the claims when not considering azithromycin specifically or whether the antibiotic has to be semi-synthetic or synthetic.
Gutierrez-Huante teaches “growth of enteropathogenic Escherichia coli E2348/69 was inhibited by bicarbonate in a dose-dependent manner, showing approximately 5% growth reduction at 5 mmol/L while kanamycin (naturally occurring) at 3-12 ug/ml inhibited growth by15%, yet when kanamycin and bicarbonate were combined at these concentrations, inhibition increased to 80%” (abstract). Gutierrez-Huante teaches the effect also occurs with gentamycin (also natural) at 5mmol/L, 10 mmol/L, 20 mmol/L, 40 mmol/L and 80 mmol/L (page 442 and figure 3). Material and methods provide for bicarbonate solutions and then adding to medium with or without antibiotic (page 444). Thus, there are two administrated forms (the solution of bicarbonate and the medium with antibiotic before the bicarbonate is added). Gentamycin and kanamycin are aminoglycoside antibiotics. Page 444 indicates “For culturing we used either a liquid Bactopeptone medium, also known as AKI medium (Iwa naga and Yamamoto 1985), composed of Bactopeptone (DIFCO or Becton Dickinson, BD) 15%, Yeast Extract (BD) 04% and NaCl 05%, or LB broth composed of Tryptone (DIFCO)”, which can be construed as semi-synthetic materials.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-4, 6, 8-9, 11, 13, 15-17, 19 and 20 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over CN102283799 (2013; in applicant IDS) and Promega, Buffers for Biochemical Reactions, copyright 2004-2012, pages 15-1 to 15-5, in applicant IDS).
CN ‘799 teaches gel-type azithromycin eye drops having azithromycin, gel matrix, isotonicity adjusting agents, preservatives, antioxidants, and buffering agents (abstract). CN ‘799 teaches buffering agents including bicarbonate buffer (paragraph 17). CN ‘799 provides for 10-30% of the buffer (paragraph 18). The pH of the composition is from 6 to 6.5 (paragraph 18). CN ‘799 provides for gel matrix including carbomers (polyacrylic acid); hydroxypropyl methyl cellulose and methyl cellulose (paragraph 11). Note that bicarbonate in CN ‘799 is bicarbonate buffer, and thus, is part of a buffer with other components such as water. CN ‘799 provides for 0.5 to 5% of azithromycin in the formulation. CN’799 teaches “Susceptible population and cause bacterial conjunctivitis by following microorganism: CDC corynebacterium G*, hemophilus influenza, staphylococcus aureus, streptococcus mitis group, streptococcus pneumoniae etc.” (English translation). CN’799 teaches treating bacterial conjunctivitis (abstract). Thus, the drops will contact the bacteria in the eye.
CN ‘799 does not teach buffer concentrations of the instant claims.
Promega provides that a bicarbonate-carbonate buffer of 0.1 M bicarbonate is made with 0.1 M (100 mM) sodium bicarbonate. When such a buffer is utilized in the compositions of ‘799, then there will be 10 to 30 mM bicarbonate in the eye drops, which is about 0.061% to 0.183% by weight. 0.183% is about 0.20 wt%.
Thus, one of ordinary skill in the art at the time of instant filing would have provided an eye drop composition of azithromycin and bicarbonate buffer along with other carriers and excipients provided by ‘799 and utilized known bicarbonate buffers having sodium bicarbonate of Promega that will provide for bicarbonate concentrations of the instant claims when combined by the teachings of ‘799. As CN ‘799 with teachings of Promega would allow for 10 to 30 mM bicarbonate, it provides for non-physiological amounts and an overlapping point with the range of claim 2. In regards to kit, CN ‘799 teaches a formulation with azithromycin and buffer and Promega teaches a buffer formulation. Thus, the items could be available separately and combined to make the final composition. Each separate composition could be considered a separable administrable form as this is toward the intended use of the kit components.
Claims 1-4, 6, 8-9, 11, 13, 17-20 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Kaushik et al (NPJ Biofilms and Microbiomes, May 25, 2016, volume 2, pages 1-12, in applicant IDS) and Tsai et al (Inflamm Res, 2009, volume 58, pages 491-501).
Kaushik teaches the aminoglycoside tobramycin can be used with bicarbonate to synergize to kill planktonic Pseudomonas aeruginosa (title and abstract). Kaushik teaches 5 mmol bicarbonate with 0.25 ug/ml tobramycin or 1 ug/ml tobramycin (page 3, second column and figure 3). Kaushik teaches a need to increase efficacy of existing antibiotics (abstract). Kaushik teaches “In addition to dosage, a reduction in the duration of tobramycin therapy would also help reduce toxic side effects and antibiotic selection pressure” (page 3, first column). I figure 1, concentrations of bicarbonate are used up to 160 mM. Kaushik teaches sodium bicarbonate (page 9) and stock solutions of tobramycin and sodium bicarbonate (page 9, antibiotics).
Kaushik does not teach azithromycin as an antibiotic as it used tobramycin in its studies, but it does motivate increasing efficacy of existing antibiotics.
Tsai teaches administration of azithromycin to cystic fibrosis mouse models and that “AZM administration was associated with significant reductions in bacterial load, decreased lung inflammation and increased levels of IFN-γ.” (abstract). Tsai teaches chronic infection with P. aeruginosa (abstract).
Thus, one of ordinary skill in the art before the time of filing would have used azithromycin (an antibiotic used for killing P aeruginosa) in combination with sodium bicarbonate as Kaushik recognizes a synergistic effect when sodium bicarbonate is combined with an antibiotic against Pseudomonas aeruginosa. Therefore, there is a reasonable expectation of success in obtaining synergistic or increased killing of these bacteria when azithromycin is used as the antibiotic along with addition of sodium bicarbonate in concentrations including those outside the physiological range found in blood. Kaushik also recognizes keeping the solutions of the antibiotic and sodium bicarbonate separate in its methods. In regards to kits, Kaushik provides for stock solutions of the antibiotic and bicarbonate, and thus, sees them as being separable compositions that can be combined before use. Kaushik’s teachings provide values including 160 mM and also note that bicarbonate synergizes with the antibiotic to enhance antibacterial effectiveness, which motivates one of ordinary skill in the art to increase levels as needed for the desired antibacterial effectiveness (MPEP 2144.05). Thus, one of ordinary skill in the art would adjust amounts of bicarbonate by routine optimization to enhance antibacterial effects of the composition.
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 1-4, 6, 8-9, 11, 13, 15-17 and 19-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 5, 6, 11, and 12 of U.S. Patent No. 10940163. Although the claims at issue are not identical, they are not patentably distinct from each other because the claim set provides for using bicarbonate in overlapping amounts along with azithromycin (a semisynthetic antibiotic) along with the ability to kill Staphylococcus bacteria. As the claims of ‘163 teaches the components, this would allow for formulations of each of these ingredients for later combination or administration as in the form of a kit.
Claims 1-4, 6, 8-9, 11, 13, 15-17 and 19-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4, 5, 6-11, 15-16, 20-22, and 27-28 of U.S. Patent No. 11779595. Although the claims at issue are not identical, they are not patentably distinct from each other because the claim set provides for using bicarbonate in overlapping amounts along with azithromycin (a semisynthetic antibiotic) along with the ability to kill Staphylococcus bacteria.
Claims 1-4, 6, 8-9, 11, 13, 15, and 17-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 6-8, and 10-16 of U.S. Patent No. 11400106. Although the claims at issue are not identical, they are not patentably distinct from each other because the claim set provides for using bicarbonate in overlapping amounts along with azithromycin (a semisynthetic antibiotic) along with the claim providing killing of bacteria and azithromycin is an antibiotic that can kill gram positive bacteria.
Claims 1-4, 6, 8-9, 11, 13, and 15-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 7-8, and 10-18 of copending application 18/236,164. Although the claims at issue are not identical, they are not patentably distinct from each other because the claim set provides for using bicarbonate in overlapping amounts along with azithromycin (a semisynthetic antibiotic) along with the ability to kill Staphylococcus bacteria. ‘164 provides for kits with multiple compositions for administration.
This is a provisional double patenting rejection as the claims have not yet been patented.
Conclusion
No claims are allowed.
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/MARK V STEVENS/
Examiner, Art Unit 1613
Prosecution Insights