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 .
Priority
The instant application, filed 02/28/2022, is a national stage entry of PCT/US20/48519, filed 08/28/2020, which claims priority to U.S. provisional application number 62/849,577, filed 08/30/2019.
Information Disclosure Statement
The Information Disclosure Statement filed on 05/25/2022 and 06/27/2025 are acknowledged and found to be in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are considered.
Restriction/Election
Applicant’s election with traverse of Group I in the reply filed on 06/27/2025 is acknowledged. Furthermore, the elections of the following species are acknowledged:
The sodium salt of deoxycholic acid
The form of a liquid composition
The second antibiotic agent of meropenem
The drug resistance against meropenem
The diagnosed infection of bacterial pneumonia
The mode of intranasal administration
The nebulizer for delivery of a jet nebulizer
With respect to the traversal of the restriction, the arguments are found not persuasive for the following reasons. Applicant sites the lack of “an undue search burden” in their traversal. This argument does not apply to lack of unity, which has been demonstrated for the instant case. The mere fact that the shared technical feature is known within the art demonstrates a lack of unity, and thus, warrants restriction.
Therefore, the requirement is still deemed proper and is therefore made FINAL.
In accordance with the MPEP § 803.02, if upon examination of the elected species, no prior art is found that would anticipate or render obvious the instant invention based on the elected species, the search of the Markush-type claim will be extended. If prior art is then found that anticipates or renders obvious the non-elected species, the Markush-type claim will be rejected. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be reexamined. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. In the event prior art is found during reexamination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final.
As per MPEP § 803.02, the Examiner will determine whether the entire scope of the claims is patentable. Applicants' elected species do not make a contribution over the prior art of record. It is been determined that the entire scope of the claims is not patentable.
Status of Claims
Claims 1-20 are pending in the instant application. Claims 12-20 are withdrawn from further consideration pursuant to 37 CFR § 1.142(b), as being drawn to a non-elected invention and species. Therefore, claims 1-11 read on an elected invention and species and are therefore under consideration in the instant application, and being examined on the merits as such.
Drawings
The drawings filed on 02/28/2022 are objected to under 37 CFR § 1.84(p)(5) because they include the following reference characters not mentioned in the description:
Figure 2: Neither GA47281Ery+Cm+Mer, GA4419Ery+Cm+Mer, GA17227Tet+Ery, TIGR4, nor D39 are described in the specification, nor in any figure key in the drawings. There is no way for any person of ordinary skill in the art to understand the results displayed in the figures without clarification of these the symbols and abbreviations used. According to 37 CFR § 1.84(p)(5), “reference characters not mentioned in the description shall not appear in the drawings.”
Corrected drawing sheets in compliance with 37 CFR § 1.121(d), or amendment to the specification to add the reference character(s) in the description in compliance with 37 CFR § 1.121(b) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR § 1.121(d).
Because of the lack of contextual information provided within the specification to interpret the drawings, or in alternative, a key describing the pertinent data to demonstrate enablement of method of the invention, the drawings are not of sufficient quality to permit examination. The drawings do not permit examination because they cannot be adequately interpreted by a person of ordinary skill in the art, as essential abbreviations describing the data have not been provided anywhere within the application.
Accordingly, replacement drawing sheets in compliance with 37 § CFR 1.121(d) are required in reply to this Office action. The replacement sheet(s) should be labeled “Replacement Sheet” in the page header (as per 37 CFR § 1.84(c)) so as not to obstruct any portion of the drawing figures. If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. Applicant is given a shortened statutory period of TWO (2) MONTHS to submit new drawings in compliance with 37 CFR § 1.81. Extensions of time may be obtained under the provisions of 37 CFR § 1.136(a) but in no case can any extension carry the date for reply to this letter beyond the maximum period of SIX MONTHS set by statute (35 U.S.C. 133). Failure to timely submit replacement drawing sheets will result in ABANDONMENT of the application.
Specification
The disclosure is objected to under 37 CFR § 1.74, for failing to provide a required detailed description of the drawings. According to MPEP § 608.01 (g),
A detailed description of the invention and drawings follows the general statement of invention and brief description of the drawings. This detailed description, required by 37 CFR § 1.71, MPEP §§ 608.01, 2161, and 2162, must be in such particularity as to enable any person skilled in the pertinent art or science to make and use the invention without involving extensive experimentation and must clearly convey enough information about the invention to show that applicant invented the subject matter that is claimed.
Presently, there is no detailed description of the drawings within the specification. An explanation of the figures and the results that they provide is missing from the specification, making the specification incomplete. The specification fails to demonstrate results of the exemplifications of the invention, alluded to in the brief description of the drawings. An amendment to the specification must provide explanation of the various abbreviations used in the drawings, as well as a detailed description of the drawings to be placed in the detailed description section of the specification. These materials, upon submission, will be reviewed for new matter.
Appropriate correction is required.
Claim Interpretation
The instant claims are subject to the following interpretation:
Claim 6 recites the limitation “the method of claim 1, wherein the second antibiotic agent is...”. However, the independent claim 1 does not comprise a second antibiotic agent. For the purposes of compact prosecution, claim 6 is interpreted to be dependent on claim 5, which recites “a second antibiotic agent.”
Claim Rejection - 35 U.S.C. § 112
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.
Claim 6 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 6 recites the limitation “the method of claim 1, wherein the second antibiotic agent is…” There is insufficient antecedent basis for this limitation in the claim, because the independent claim 1 does not comprise a second antibiotic agent. In order to overcome the rejection, the claim may be amended to depend on claim 5.
Claim Rejections - 35 U.S.C. § 103
The following is a quotation of pre-AIA 35 U.S.C. § 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-5 are rejected under 35 U.S.C. § 103 as being unpatentable over Gal-Mor and Rahav (WO 2017149536 A1, published September 8, 2017) in view of Pozzi et al (J Clin Microbiol, Vol 27 Iss 2, pg. 370-3722, published February 1989), hereinafter Pozzi.
The instant claims are drawn to methods of treating or preventing Streptococcus pneumoniae infections by administering an effective amounts of sodium deoxycholate.
Gal-Mor and Rahav disclose methods of increasing susceptibility of bacteria to antibiotic treatment (Abstract) by contacting bacteria with an effective amount of bile acid or bile salt (claim 1). Gal-Mor and Rahav disclose that suitable bile acids/salts (page 11, likes 23 and 24) include deoxycholic acid (page 11, line 5), and more specifically deoxycholate (line 11, lines 26 and 27). Gal-Mor and Rahav teaches wherein the bile salt includes a sodium cation (Na+) (page 11, lines 13 and 14). The invention is discloses as being effective in treating Streptococcus (page 15, line 30). According to one embodiment, the bile acid or bile salt comprises deoxycholic acid at a concentration of 0.01-10 % w/v and according to a specific embodiment, the concentration of deoxycholic acid in the composition is at least about 0.01 %, 0.1 %, 1 %, 2%, 4 %, 6 %, 8 % or 10 % w/v (page 28, lines 15-18). The disclosure further details the combination of the bile acid salt with an antibiotic (page 28, lines 19-26). Formulations of the disclosure by Gal-Mor and Rahav may be liquids and sprays (page 31, lines 22-24). The disclosure further details wherein the bacteria are resistant to antibiotics (claim 10). The disclosure teaches a method of inhibiting bacterial growth, the method comprising contacting bacteria with an effective amount of a bile acid or a bile salt (claim 3). The disclosure further details increasing susceptibility of bacteria to antibiotic treatment by contacting the bacteria with an effective amount of a bile acid or a bile salt (claim 5). Finally, the disclosure details the application of the composition to drinking water (claim 37).
Although Gal-Mor and Rahav teach the genus of Streptococcus as a specific bacterial genus to be treated with the composition, they do not teach the use of the composition in a method of treating or preventing infections of the instantly claimed species of Streptococcus pneumoniae.
The deficiencies of Gal-Mor and Rahav are remedied by Pozzi, which teaches the use of sodium deoxycholate in inducing autolysis in a range of 287 clinical isolates of Streptococcus pneumoniae from different geographical sources (Abstract). The autolysis is mediated by N-acetylmuramoyl-L-alanine amidase (page 370), found to be unique to Streptococcus pneumoniae in comparison to other species (Abstract, pages 370 and 371). Pozzi provides a clear mechanism and the specific motivation for targeting Streptococcus pneumoniae with sodium deoxycholate.
A person of ordinary skill in the art prior to the effective filing date of the instantly claimed application would have found it prima facie obvious to combine the teachings of Gal-Mor and Rahav, which provides clinically suitable concentrations of sodium deoxycholate in addressing a bacterial infection and antibiotic resistant bacteria, thus, enabling a well-established formulation and delivery method in the art, to be applied to the species of Streptococcus pneumoniae taught by Pozzi to autolyse in the presence of sodium deoxycholate. The combination of said established effective formulation to a different bacterial species, known to be subject to cellular destruction in the presence of sodium deoxycholate, would have yielded a reasonable expectation of success the person of ordinary skill in the art seeking a practical and effective treatment for Streptococcus pneumoniae infection.
Regarding claim 1, Pozzi teaches that sodium deoxycholate induces rapid autolysis in Streptococcus pneumoniae infection, (page 370-312 and Table 1). Gal-Mor and Rahav teach wherein the formulation outlined above may be applied to drinking water (claim 37). A person of ordinary skill in the art would have recognized that such administration via drinking water offers a practical means of delivering a therapeutically effective dose of sodium deoxycholate to patients, particularly in community or clinical settings were oral or internal administration is preferred. This teaching would have motivated the person of ordinary skill in the art to adapt the formulations taught by Gal-Mor and Rahav for direct patient administration, and would have expected to yield systemic or localized therapeutic benefits in the treatment or prevention of Streptococcus pneumoniae according to the teachings of Pozzi.
Regarding claims 2-4, Gal-Mor and Rahav teach pharmaceutical compositions containing sodium deoxycholate at concentrations that overlap with the claimed ranges. Gal-Mor and Rahav, teaches pharmaceutical compositions containing the at least about 0.01 %, 0.1 %, 1 %, 2%, 4 %, 6 %, 8 % or 10 % w/v of deoxycholic acid/salts(page 28, lines 15-18). With respect to the range of sodium deoxycholate taught by Gal-Mor and Rahav, and the instantly claimed ranges, it is noted that the courts have stated
where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP § 2144.05.01).
The courts have also found that,
“where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP § 2144.05 II.
Therefore, the claimed ranges merely represent an obvious variant and fully overlap with the values of the cited prior art.
Regarding claim 5, Gal-Mor and Rahav detail the combination of the bile acid salt with an antibiotic (page 28, lines 19-26).
Claims 1, 6 and 7 are rejected under 35 U.S.C. § 103 as being unpatentable over Gal-Mor and Rahav (see earlier citation), in view of Pozzi (see earlier citation), as applied to claims 1-5 above, and further in view of Nakano et al. (Emerg Infect Dis, Vol 24, Iss 2, pg. 275–283, published February 2018), hereinafter Nakano.
Claims 5-7 further claim administering a second antibiotic such as meropenem, and treating a subject diagnosed with meropenem-resistant bacteria.
Gal-Mor and Rahav in view of Pozzi is as set forth above, and applied to claim 1.
Gal-Mor and Rahav in view of Pozzi do not teach the administration of a second antibiotic such as meropenem, and treating a subject diagnosed with meropenem-resistant bacteria.
The deficiencies of Gal-Mor and Rahav and Pozzi are remedied by Nakano, who teaches a meropenem-resistant strain of Streptococcus pneumoniae (Title, Abstract), highlighting an urgent clinical need for alternative and combination therapies (page 276 and 281).
A person of ordinary skill in the art prior to the effective filing date of the instantly claimed would have found it prima facie obvious to combine the teachings of Gal-mor and Rahav and Pozzi as set forth above, with the teachings of Nakano, which teaches a specific meropenem-resistant strain of Streptococcus pneumoniae, in order to treat the antibiotic resistant strain. The combination would have had a reasonable expectation of success in yielding a practical and effective treatment for meropenem-resistant Streptococcus pneumoniae infection.
Regarding claim 5, Gal-Mor and Rahav teaches the use of deoxycholic acid in combination with other antibacterial agents. According to MPEP § 2144.06 (I), combining equivalents known for the same purpose is rendered obvious. The courts have said,
It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.).
Thus, a person of ordinary skill in the art would have found it obvious to combine sodium deoxycholate with meropenem, as they are both known to have antibiotic properties.
Regarding claim 6, Gal-Mor and Rahav teach the use of deoxycholate in treating an antibiotic resistant bacterial strain (claim 10). Pozzi teaches wherein sodium deoxycholate leads to the cellular destruction Streptococcus pneumoniae. Nakano highlights an urgent clinical need for alternative and combination therapies (page 276 and 281). The teachings of Nakano provide specific clinical motivation to use meropenem due to the emergence of a resistant strain, discussed in the disclosure (Title, Abstract). The person of ordinary skill in the art would have a reasonable expectation that the use of sodium deoxycholate could lessen resistance to meropenem, as sodium deoxycholate taught to destroy cells of Streptococcus pneumoniae, as taught by Gal-Mor and Rahav (claim 5). The combination of these teachings would directly motivate a person of ordinary skill in the art to combine meropenem with a therapeutically effective antibiotic resistant anti-bacterial composition comprising sodium deoxycholate in the treatment of a meropenem-resistant strain, reasonably expected to undergo cellular destruction the presence of sodium deoxycholate, in order to increase susceptibility of Streptococcus pneumoniae to meropenem treatment.
Regarding claim 7 Nakano discusses the clinical challenge of meropenem-resistant Streptococcus pneumoniae infection. The aforementioned urgent clinical need for viable treatments and therapies for the novel meropenem-resistant strain of Streptococcus pneumoniae highlighted by the teachings of Nakano, serve as direct motivation for a person of ordinary skill in the art to apply the teachings of Gal-Mor and Rahav and Pozzi to treat the meropenem resistant strain.
Claims 1, and 8-11 are rejected under 35 U.S.C. § 103 as being unpatentable over Gal-Mor and Rahav (see earlier citation), in view of Pozzi (see earlier citation), as applied to claims 1-5, in further view of Safdar et al. (Expert Opin Drug, Vol 8, Iss 4, pg. 435-449, published June 21, 2009), hereinafter Safdar.
The instant claims are drawn to methods of treating or preventing Streptococcus pneumoniae infections by administering an effective amount of sodium deoxycholate to a subject diagnosed with bacterial pneumonia, by way of aerosolization delivered by intranasal jet nebulizer.
Gal-Mor and Rahav in view of Pozzi is as set forth above, and is applied to claim 1.
Gal-Mor and Rahav do not disclose practical formulations or administration routes for human or pharmaceutical use (i.e. liquid, aerosol, nebulizer etc.).
The deficiencies of Gal-Mor and Rahav and Pozzi are remedied by Safdar, who teaches the use of an aerosolized lysate to prevent and treat pneumonia caused by Streptococcus pneumoniae (Title, Figure 2). Safdar teaches that Streptococcus pneumoniae is the most common cause of bacterial pneumonia (page 438). Further, Safdar teaches the use of air-jet nebulizer as the choice of pulmonary drug delivery system (Abstract). Furthermore, the inhalation of the lysate is shown to improve survival of Streptococcus pneumoniae (page 438).
A person of ordinary skill in the art prior to the effective filing date of the present application would have found it prima facie obvious to combine the teachings of Gal-Mor and Rahav and Pozzi as set forth in the rejection of claims 1-5 above, with the inhaled nebulizer treatment shown to be effective in treating Streptococcus pneumoniae by Safdar, in order to enable a well-established formulation and delivery method to effectively treat bacterial pneumonia. The combination would have had a reasonable expectation of success in yielding a practical and effective treatment in treating pneumonia, most often caused by Streptococcus pneumoniae by way of an inhaled medicament.
Regarding claim 8, Safdar teaches that Streptococcus pneumoniae is the most common cause of bacterial pneumonia (page 438). The ability of sodium deoxycholate to induce rapid autolysis in Streptococcus pneumoniae serves as direct motivation to use sodium deoxycholate to treat bacterial pneumonia, most often caused by Streptococcus pneumoniae.
Regarding claim 9, Safdar teaches the inhalation of an aerosolized lysate is shown to improve survival in mice suffering from Streptococcus pneumoniae infection (page 438).
Regarding claims 10 and 11, Safdar teaches air-jet nebulizers as a well-established choice for pulmonary drug delivery system (Abstract). With respect to intranasal administration, it is well recognized with in the art that jet nebulizers belong to the genus of intranasal administration.
Correspondence
No claim is allowed.
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/SOPHIA P HIRAKIS/Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623