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 . Claims included in the prosecution are claims 30, 31, 35, 38, 39, 41, 50 and 51.
NOTE: Since Applicant did not file a new claim set, it is assumed that the claims under prosecution are of the ones filed on 04/02/2025.
Applicants' arguments, filed 10/14/2025, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 103
The following is a quotation of 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 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.
1. Claims 30, 35, 38, 39, 41 and 51 are rejected under 35 U.S.C. 103 as being unpatentable over Huigens et al. (WO 2017/053696 A2, Mar. 30, 2017) (hereinafter Huigens).
Huigens discloses halogenated quinoline derivatives, such as compounds of Formula (I’):
PNG
media_image1.png
354
296
media_image1.png
Greyscale
.
The halogenated quinoline derivates may be useful in preventing or treating a microbial infection (e.g., a bacterial infection) in a subject (abstract). RG and RE are each a halogen. RC may be H. RH may be
PNG
media_image2.png
184
172
media_image2.png
Greyscale
, wherein RD and RB may each be H, RA may be a substituted or unsubstituted alkyl, and RK’ may be a substituted or unsubstituted C1-6 alkyl (claim 1). Halogens include chlorine (-Cl) (¶ [0066]). RA may be specifically Me (¶ [00124]). Examples of C1-6 alkyls include methyl (¶ [0046]). The compound may be administered concurrently with, prior to, or subsequent to, one or more additional pharmaceutical agents, which are different from the compound and may be useful as, e.g., combination therapies (¶ [00246]). Exemplary additional pharmaceutical agents include a tetracycline (e.g., doxycycline) (¶ [00247]). The bacterium may be a multidrug-resistant bacterium. The bacterium may be a Gram-positive bacterium. The bacterium may be a Streptococcus species, such as Streptococcus pneumoniae (¶ [00267]).
The prior art discloses the claimed zinc ionophore for treating a bacterial infection in a subject (see abstract and claim 1) in combination with an additional pharmaceutical agent (see ¶ [00246]).
The prior art is not anticipatory insofar as in order to arrive at the claimed compound one must select the substituents of the compound from various lists/locations in the reference. It would have been obvious, however, to make the combination since all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. See MPEP 2143(I)(A).
In regards to instant claim 30 reciting wherein the zinc ionophore confers sensitivity of the bacterium to the antibiotic and increases the amount of zinc in the bacterium, the prior art discloses substantially the same compound as the claimed invention. Therefore, the compound of the prior art necessarily confers sensitivity of the bacterium to the antibiotic and increases the amount of zinc in the bacterium like the claimed invention.
2. Claim 31 is rejected under 35 U.S.C. 103 as being unpatentable over Huigens et al. (WO 2017/053696 A2, Mar. 30, 2017) (hereinafter Huigens) in view of Jordan et al. (US 7,846,919, Dec. 7, 2010) (hereinafter Jordan), as evidenced by Barnham et al. (US 2008/0161353, Jul. 3, 2008) (hereinafter Barnham).
The teachings Huigens are discussed above. Huigens does not disclose wherein the compound is in combination with a pharmaceutically acceptable zinc (II) salt.
However, Jordan discloses a composition for use in treating epithelial lesions formed of a combination of ingredients comprising 8-hydroxyquinoline and zinc bonded to said 8-hydroxyquinoline (claim 1). The zinc is provided in the composition as zinc chloride (claim 4).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have the compound of Huigens in combination with zinc chloride motivated by the desire to additionally treat epithelial lesions since the combination of an 8-hydroxyquinoline and zinc treats epithelial lesions as taught by Jordan.
As evidenced by Barnham, the compound of Huigens is 8-hydroxyquinoline derivative PBT 1033 (pages 9 and 65):
PNG
media_image3.png
156
330
media_image3.png
Greyscale
.
3. Claim 50 is rejected under 35 U.S.C. 103 as being unpatentable over Huigens et al. (WO 2017/053696 A2, Mar. 30, 2017) (hereinafter Huigens) in view of Jordan et al. (US 7,846,919, Dec. 7, 2010) (hereinafter Jordan), and further in view of Nguyen et al. (Structures of the copper and zinc complexes of PBT2, a chelating agent evaluated as potential drug for neurodegenerative diseases, Nov. 4, 2016) (hereinafter Nguyen).
The teachings of Huigens and Jordan are discussed above. Huigens and Jordan do not disclose wherein the compound and the zinc (II) salt are in the form of a zinc (II) coordination complex.
However, Nguyen discloses Zn(PBT2)2Cl (Figure 5 motif B).
PNG
media_image4.png
154
168
media_image4.png
Greyscale
Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. Jordan discloses wherein the combination of an 8-hydroxyquinoline and zinc treats epithelial lesions. Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to incorporated Zn(PBT2)2Cl as the halogenated quinoline derivative of Huigens since it is a known and effective 8-hydroxyquinoline in combination with zinc as taught by Nguyen.
Response to Arguments
Applicant argues that to arrive at PBT2, a skilled artisan would need to make at least 15 different selections out of distinct lists without any motivation to do so.
The Examiner does not find Applicant’s argument to be persuasive. Choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success supports a conclusion of obviousness. See MPEP 2143(I). Huigens discloses in claim 1 a finite number of substituents for each R group of Formula (I’). Therefore, Applicant’s argument that PBT2 would not be obvious because one would have to choose from different selections is not persuasive. Furthermore, it should be noted that according to the sixth page of Ex parte Perrier, Appeal 2012-003888 (PTAB (2014)) (USSN 11/174,414):
We agree that Roos discloses a number of polymers and crosslinkers, but Roos makes plain that the ordinary artisan would have known to combine any one of the disclosed polymers with any one of the disclosed crosslinkers for synthesis of the polymer nework compositions (FF 1-6). See Merck & Co., Inc. v. Biocrafi Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989). (‘That the ‘813 patent discloses a multitude of effective combinations does not render any particular formulation less obvious’); In re Corkill, 771 F.2d 1496, 1500 (Fed. Cir. 1985)(obviousness rejection of claims affirmed in light of prior art teaching that ‘hydrated zeolites will work’ in detergent formulations, even though the inventors selected the zeolites of the claim claims from among ‘thousands’ of compounds).
Thus, the Board in that case applied case law supporting the proposition that a multitude of effective combinations does not render any particular formulation less obvious. Moreover, one of ordinary skill in the art would have had motivation to make the selections since Huigens discloses a formula and in order to arrive at a compound, one would have had to make selections. Additionally, Applicant has not shown wherein PBT2 is more effective than the other compounds disclosed by Huigens, thus making the use of PBT2 unexpected. As such, Applicant’s argument is unpersuasive.
Applicant argues that one would not be able to predict whether PBT2 would have antimicrobial activity or not. Out of the limited number of compounds tested in the art, some of the compounds have antimicrobial activity, whereas other compounds do not have any antimicrobial activity. For example, RA-HQ-11 is inactive in Table 1.
The Examiner does not find Applicant’s argument to be persuasive. Huigens discloses in the abstract wherein the compounds of Formula (I’) are antimicrobial agents and are useful in preventing or treating a microbial infection, inhibiting the growth and/or reproduction of a microorganism, killing a microorganism, inhibiting the formation and/or growth of a biofilm, reducing or removing a biofilm, and/or disinfecting a surface. Therefore, one of ordinary skill in the art would have reasonably expected the compounds of Formula (I’), which includes PBT2, to have antimicrobial activity. With regards to RA-HA-11, this compound is a compound of Formula (I) and not Formula (I’). Applicant has not shown wherein not all compounds of Formula (I’) have antimicrobial activity. Also, RA-HA-11 has antimicrobial activity because as shown in Table 2 of Huigens, it has a MIC value. Additionally, although RA-HA-11 is unable to eradicate MRSA-2 biofilms at 1,000 µM, that doesn’t mean RA-HA-11 is unable to treat other bacterial strains, unable treat MRSA-2 biofilms at a different concentration, or unable to treat at least a small amount of the MRSA-2 biofilm. Treating other bacterial strains, MRSA-2 biofilms at a different concentration, and at least a small amount of the MRSA-2 biofilm still indicates antimicrobial activity. As such, Applicant has not shown wherein one of ordinary skill in the art would not expect the compounds of Huigens to have antimicrobial activity and Applicant’s argument is unpersuasive.
Applicant argues that while Huigens demonstrates that some of the compounds disclosed can kill antibiotic resistant bacteria directly, it does not show or teach that they can cause increased efficacy of antibiotics that the bacteria are already resistant to.
The Examiner does not find Applicant’s argument to be persuasive. As discussed in the rejection, the prior art discloses substantially the same compound as the claimed invention. Therefore, the compound of the prior art necessarily confers sensitivity of the bacterium to the antibiotic. The discovery of a previously unappreciated property of a prior art composition does not render the old composition patentably new to the discoverer. See MPEP 2112(I). As discussed in the rejection, it was known in the art to administer the compound of formula (I’), which includes PBT2, with an antibiotic. Applicant discovering another reason to administer the compound with an antibiotic does not make using the compound with an antibiotic nonobvious. As such, Applicant’s argument is unpersuasive.
Applicant argues that paragraph [00355] of Huigens describes that iron in the bacterium decreased, not increased, and stated that magnesium and copper had no effect. This is completely opposite to the mechanism of action of PBT2. These results would teach away from a zinc-dependent ionophore mechanism of action.
The Examiner does not find Applicant’s argument to be persuasive. It is unclear how having iron in the bacterium decreased means that zinc in the bacterium cannot be increased. Also, the PBT2 of Huigens is substantially the same as PBT2 claimed. Therefore, it is unclear how the PBT2 of Huigens would not have substantially the same mechanism of action as the PBT2 claimed. As such, Applicant’s argument is unpersuasive.
Applicant argues that the utility of increasing the amount of zinc in a bacterium for overcoming antibiotic resistance was not known prior to the conception of the present invention.
The Examiner does not find Applicant’s argument to be persuasive. As discussed above, the discovery of a previously unappreciated property of a prior art composition does not render the old composition patentably new to the discoverer. Therefore, Applicant discovering that PBT2 has the property of being a zinc ionophore does not make using PBT2 nonobvious. As such, Applicant’s argument is unpersuasive.
Applicant argues that Jordan, Barnham, and Nguyen do not remedy the deficiencies of Huigens.
The Examiner submits that arguments regarding Huigens are addressed above and are unpersuasive. Therefore, the rejections with Jordan, Barnham, and Nguyen are maintained.
Conclusion
Claims 30, 31, 35, 38, 39, 41, 50 and 51 are rejected.
Claims 36, 40, 42 and 53-59 have been withdrawn.
No claims are allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TRACY LIU whose telephone number is (571)270-5115. The examiner can normally be reached Mon-Fri 9 am - 5 pm.
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, Ali Soroush can be reached at 571-272-9925. 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.
/TRACY LIU/Primary Examiner, Art Unit 1614