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 .
Claim Status
Claims 10, 14-21 and 24-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Claims 1-2 are under consideration in this office action.
Withdrawn Objections/Rejections
Any rejection of record pertaining to cancelled claims 4-5, 8, and 13 is rendered moot by applicant's cancellation of said claims.
The objection of claim 1 is withdrawn in view of applicant’s amendment.
New Rejections Necessitated by Amendment
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.
Claims 1-2 are rejected under 35 U.S.C. 103 as being unpatentable over US 6,399,078 published June 4, 2002 (“DeVico”; IDS from 7/7/2021) in view of Hunter et al, published December 15, 1995 (IDS from 7/7/2021) and Ishiyama et al, published August 1976 (instant PTO-892).
DeVico teaches compositions and methods for treating bacterial infection, including Staphylococcus aureus, by administering the immunomodulator MIP-1a/CCL3 (column 9, ln 1-5; column 10, ln 2), as required by claim 1. The compound can be administered systemically or topically (column 28, ln 41-45). While Devico does not explicitly identify MIP-1a by its alternative name CCL3, it is known in the art that the MIP-1a protein was renamed CCL3 in 2000, as evidenced by Menten et al (see IDS from 9/8/2022) (pg 457, “Nomenclature of MIP-1”). DeVico teaches that chemokines are beneficial in wound healing (column 14, ln 30-50), as in instant claim 2.
With regards to Methicillin-resistant Staphylococcus aureus (MRSA), as in claim 1, it is the Office’s position that this species within the Staphylococcus genus can be at once envisaged from the prior art because the species within this genus (e.g. MRSA and non-MRSA strains of S. aureus) are sufficiently limited and well delineated (i.e. two options); see MPEP 2131.02(III) and In re Petering (wherein the courts determined that a reference describing a generic formula encompassing about 20 compounds was found to anticipate each of the 20 species without specifically naming them).
DeVico does not teach an Asp>26Ala substitution of CCL3 to reduce aggregation, as required by claim 1.
Hunter et al teaches a variant of human MIP-1alpha (i.e. CCL3) that carries a single amino acid substitution of Asp26>Ala (pg 4400, column 2, ln 11-12), as in instant claim 1. This variant has a reduced tendency to form large polymers at physiologic pH and ionic strength, which greatly increases solubility, thereby facilitating production and clinical formulation (pg 4400, column 2,ln 12-15).
Given that DeVico teaches a method of treating an infection by administering CCL3 and further given that Hunter et al teaches a mutant of CCL3 that exhibits decreased aggregation, it would have been obvious to one of ordinary skill in the art to apply the amino acid substituted CCL3 taught by Hunter in the method of DeVico and have a reasonable expectation of success. The motivation comes from the Hunter reference, which teaches that the genetically engineered variant of MIP-1a has “dramatically improved pharmaceutical properties” without affecting in vitro assessed biologic function (pg 4407, column 2, paragraph 4). One would have been motivated to combine these references because of the art recognized need to generate stable pharmaceutical formulations for the treatment of microbial infection related to cytokine receptor interactions. Further, the artisan has good reason to pursue the known options within their technical grasp to obtain predictable results. Such would amount to the combining of prior art elements according to known methods to achieve predictable outcomes.
Devico in view of Hunter et al does not teach a combination therapy comprised of CCL3 with the antibiotic tobramycin for treating an infection at a surgical site or wound in a subject with diabetes.
Ishiyama teaches that the antibiotic tobramycin is active against Pseudomonas aeruginosa in patients with severe surgical infections (pg S178), as in the infection of instant claim 1 and the surgical site wound of instant claim 2.
Given that DeVico in view of Hunter et al teaches a method of treating infection with CCL3 with the claimed mutations and further given that Ishiyama teaches treatment of infection with tobramycin, the claimed method would have been obvious to one of ordinary skill in the art. Section 2144.06 of the MPEP provides guidance as to obviousness of art recognized equivalence for the same purpose: "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 they having been individually taught in the prior art. In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted). Accordingly, the teachings of DeVico in view of Hunter et al and Ishiyama render obvious the method of claims 1-2 directed to a combination therapy of CCL3 and tobramycin, because the ordinary artisan would expect that the combined effect would be at least additive, with potential for a synergistic effect, thus enhancing the therapeutic efficacy of the treatment.
Regarding the limitation of claims 1-2 drawn to a subject with diabetes, the cited references do not teach a subject with diabetes. Rather, Devico in view of Hunter et al and Ishiyama et al teach a method of treating an infection by administering CCL3 having an Asp26>Ala substitution in combination with tobramycin. The preamble phrase “in a subject with diabetes” is not limiting because it merely identifies a subgroup of patients and does not impose any affirmative treatment step or functional limitation on the claimed method. Even if the diabetic-patient is considered limiting, it would have been obvious to apply the known method of treating an infection of Devico to diabetic patients because diabetic patients are recognized as a population susceptible to infection. As the references teach treatment of infection generally without excluding diabetic subjects, absent evidence to the contrary, selecting diabetic patients from the broader population would have been a routine matter of selecting a patient subgroup.
Response to Arguments
Applicant’s arguments filed May 6, 2026 with respect to the rejection under 35 U.S.C. 103 of claims 1-2 as being unpatentable over DeVico in view of Hunter et al. and Heslet have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Regarding the amendment of claim 1 to include the antibiotic tobramycin, applicant asserts that combining tobramycin with CCL demonstrates unexpected synergistic effects relative to monotherapy (remarks, pg 2). Although it is clear that the combination treatment is better than each treatment alone (see Figures 3 and 9 of the disclosure), it is not clear that the combination treatment is associated with unexpected synergy. An example of unexpected synergy would be a therapeutic response that is significantly greater than the sum of each monotherapy response. Looking at Figure 9 of applicant’s disclosure, both CCL3 treatment and tobramycin treatment alone increase IL1beta and TNFalpha levels in wound tissue, but the combination therapy response is not unexpectedly greater than the sum of each monotherapy response. The data is Figure 3 are more ambiguous because there is not one graph with all the required treatment conditions (i.e. PBS, CCL3, tobramycin, and CCL3+tobramycin), and the y-axes are different for subparts A and B. The evidence for synergy is not persuasive. Moreover, a greater than additive effect alone is not necessarily sufficient to overcome a prima facie case of obviousness because such an effect can either be expected or unexpected. Applicant must further show that the results were greater than those which would have been expected from the prior art to an unobvious extent, and that the results are of a significant, practical advantage. Ex parte The NutraSweet Co., 19 USPQ2d 1586 (Bd. Pat. App. & Inter. 1991) (see MPEP 716.02(a)I).
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 JENNIFER BENAVIDES whose telephone number is (571)272-0545. The examiner can normally be reached M-F 9AM-5PM (EST).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at (571)272-0911. 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.
Jennifer Benavides
Examiner
Art Unit 1675
/JENNIFER A BENAVIDES/Examiner, Art Unit 1675
/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675
Prosecution Insights