DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on February 4th, 2026 has been entered.
Claim Status
Claims 1-8 and 12-24 are pending. Claims 4, 5 and 15-20 are withdrawn as being directed to a non-elected invention and species as set forth in the restriction requirement filed on February 13th, 2025. Claims 1-3, 6-8 and 12-14 are up for examination.
Response to Arguments
Applicant's arguments filed February 4th, 2026 have been fully considered but they are not persuasive.
Applicant argues that:
The examples in Owens do not demonstrate preparation of an allograft bone tissue using a zin-containing solution. Nor does the experimental data in Owens demonstrate that he treatment of acellular dermal tissue with zinc sulfate solution in the absence of chelating agent leads to reduced bacterial concentrations compared to control samples.
In Example 3 of Owens, acellular porcine dermal tissue samples were incubated in either a 1mM NHS-IDA solution alone for 4 hours, a 1mM zinc sulfate solution alone, or in both NHS-IDA and zinc sulfate solutions. Example 3 does not disclose the duration of contact between the tissue graft and the zinc sulfate solution. Some samples were then rinsed in saline overnight to remove excess or unbound zinc. Tissue sample were then incubated overnight with approximately 1e6 cells of S. aureus. The bacteria concentrations for samples that were rinsed to remove excess or unbound zinc are shown the “Overnight Wash” group in Fig. 3, and those for the samples that were not rinsed are shown in the “No Wash” group.
The tissue sample contacted with zinc only in the Overnight Wash group showed a bacterial CFU count that is comparable to the inoculum and a less than three-log reduction compared to the control sample. In other words, the zinc was bacteriostatic and not antimicrobial. Only when the dermal tissue was first treated with a chelating agent could it then bind zinc to achieve a log10 reduction in bacterial CFU of less than 1, as shown by the IDA-Zinc data in the Overnight Was group. Since Owens only achieved antimicrobial effect with IDA-zinc functionalization, this suggests that chelation is necessary for durable, wash-resistant antimicrobial efficacy in functionalized dermal tissue, rather than transient zinc sulfate.
The examples of Owens only used acellular porcine dermal tissue, which is a skin-derived tissue different from the bone tissue used in the examples of the present application, and to which the claims are now limited. Bone tissue contains hydroxyapatite which is not present in skin tissue. Zinc naturally binds to the negatively charged phosphate groups in hydroxyapatite without any prior modification to the bone tissue.
The present application shows that zinc alone directly binds to bone tissue and can achieve antimicrobial effect without a chelating agent after a short period of 1, 3, 7, 15, 30 minutes, even when the samples are rinsed to remove excess zinc. Examples in Owens do not show this binding effect between zinc and the dermal tissue, especially after rinsing.
As Owens does not demonstrate that bone tissue functionalized with zinc alone, in absence of any chelating agent, confers antimicrobial properties even after rinsing to remove excess zinc, the claims as amended herein are nonobvious over Owens.
The Examiner would respectfully respond that:
It is first noted that the claims specifically state inhibiting or controlling growth. As shown in Figure 3 of Owens, the control increases to nearly an 8 log CFU, while the overnight wash treated with zinc only remains substantially stable with the inoculated sample at just below a 6 log CFU as shown below.
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Thus, at the very least, Owens teaches controlling growth even in the overnight wash grouping. Nonetheless and more importantly, the reference specifically teaches inhibiting and reducing the bacterial count as compared to the inoculated sample in the “No Wash” sample to below a 2 log CFU. As such, Owens fairly clearly teaches inhibiting and even reducing growth of bacteria in the “No Wash” sample when treating the tissue only with a zinc antimicrobial solution, and even controlling growth of bacteria in the “Overnight Wash” sample when treating the tissue only with a zinc antimicrobial solution.
Further to the point that the examples of Figure 3 are treated on dermal tissue, although said examples are for dermal tissue (paragraph 105), Owens specifically discloses that the methods presented therein are for bone tissue grafts as well (paragraphs 33, 53 and 57). And because Owens discloses controlling growth of an inoculated tissue graft treated only with zinc when overnight washed & further reducing and inhibiting growth of an inoculated tissue graft treated only with zinc when said graft is not washed; then one of ordinary skill would be motivated to treat a bone tissue graft with a zinc compound without prior surface modification in order to control, reduce and inhibit the growth of bacteria on said graft because Owens teaches the advantages of doing so, and teaches that the methods are proper for bone tissue grafts. Thus, these limitations are met by Owens.
As such, this response is not persuasive.
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, 6-8, 14 and 21-24 are rejected under 35 U.S.C. 103 as being unpatentable over Owens et al. (U.S. Publication No. 2013/0280223).
Concerning claims 1, 2, 6-8, 21 and 22, Owens discloses a method for preparing a bone tissue graft, comprising:
Providing an allograft bone tissue (concerning claims 7 & 8; paragraph 33); and
Applying to the allograft bone tissue an antimicrobial solution (paragraphs 75-78) comprising a zinc sulfate (concerning claim 2) compound by soaking (concerning claim 6) the tissue graft with the antimicrobial solution (paragraph 105), thereby causing the zinc compound to bond directly to the bone tissue graft and modify the surface of the bone tissue graft (paragraphs 75-83), wherein the bone tissue graft surface is contacted with the antimicrobial solution without prior surface modification (i.e., Figure 3, Zinc only) and the antimicrobial solution intrinsically exhibits antimicrobial activity of inhibiting or controlling growth of Mycobacterium tuberculosis in the tissue graft and provides deep tissue cleaning (paragraphs 75-83 and 105).
Note that although the examples of Figure 3 are for dermal tissue (paragraph 105), Owens specifically discloses that the methods presented therein are for bone tissue grafts (paragraphs 33, 53 and 57), and because Owens discloses controlling growth of an inoculated tissue graft treated with zinc only when overnight washed & further reducing and inhibiting growth of an inoculated tissue graft treated with zinc only when said graft is not washed; then one of ordinary skill would be motivated to treat a bone tissue graft with a zinc compound without prior surface modification in order to control, reduce and inhibit the growth of bacteria on said graft because Owens teaches the advantages of doing so, and teaches that the methods are proper for bone tissue grafts. Thus, these limitations are met by Owens.
Owens does not appear to disclose contacting the tissue graft with the antimicrobial solution for about 10 minutes to about three hours (or two hours, or one hour concerning claims 21 & 22). Nonetheless, the Courts have held 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." See In re Aller, 220 F.2d 454, 456,105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.). Thus, it would have been well within the purview of one of ordinary skill in the art to contact the tissue graft with the antimicrobial solution for about 10 minutes to about three hours (or two hours, or one hour) in order to successfully inhibit the growth of harmful bacteria on said tissue for a given application based on various factors such as desired inhibition, concentration of antimicrobial, outside environmental factors, etc.; as the time exposing a component to an antimicrobial is a well-known a result effective variable that one of ordinary skill would optimize through routine experimentation. Furthermore, it is noted that the Applicant has not claimed a contact time short enough (say 30 seconds or even ten minutes) in which one of ordinary skill would not be inclined or think sufficient to create the antimicrobial efficacy needed; as a contact time of three hours (or even 1 hour) is readily considered within the purview of one of ordinary skill.
As such, claims 1, 2, 6-8, 21 and 22 do not create a patentable distinction over Owens.
Concerning claim 14, Owens continues to disclose that the antimicrobial solution further comprises a pharmaceutically acceptable vehicle, excipient, diluent or adjuvant (paragraphs 76 and 105).
With respect to claims 23 & 24, in light of the Applicant’s specification, Owens continues to disclose that the antimicrobial solution comprises an antimicrobial active consisting of a zinc compound (paragraphs 76 and 105).
Claims 3, 12 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Owens et al. (U.S. Publication No. 2013/0280223) Qayyum et al. (Non-Patent Literature titled “The Antimicrobial Activity of Different Zinc Salts”).
Owens is relied upon as set forth above. Owens does not appear to disclose that the zinc compound is zinc chloride. Qayyum discloses the antimicrobial efficacy of zinc compounds against S. aureus, S. pyogenes, Salmonella typhi and Candida albicans, wherein the compounds included both zinc sulfate and zinc chloride (Summary). The reference continues to disclose that zinc chloride had superior antimicrobial efficacy versus zinc sulfate against every pathogenic micro-organism tested (See tables 1-4). As such, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize zinc chloride in the method of Owens because Qayyum discloses that zinc chloride had superior antimicrobial efficacy versus zinc sulfate against every pathogenic micro-organism tested.
As such, claim 3 is not patentable over Owens in view of Qayyum.
With respect to claims 12 & 13, while Owens in view of Qayyum further discloses soaking the zinc chloride on the tissue graft, Owens in view of Qayyum does not appear to disclose that the applied solution comprises from about 5-10% zinc chloride. Nonetheless, the Courts have held 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." See In re Aller, 220 F.2d 454, 456,105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.). Thus, it would have been well within the purview of one of ordinary skill in the art to soak the tissue graft in a 5-10% zinc chloride solution in order to effectively kill the desired number of pathogens on a particular tissue graft for a given application, as such is considered a result effective variable that would be optimized by one of ordinary skill during routine experimentation.
Therefore, claims 12 & 13 are not patentable over Owens in view of Qayyum as well.
Conclusion
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/KEVIN JOYNER/Primary Examiner, Art Unit 1799