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 Status
Receipt of Remarks/Amendments filed on 10/23/2025 is acknowledged. Claims 1-16 are currently pending. Claims 1-14 have been withdrawn. Accordingly, claims 15-16 are presented for examination on the merits for patentability.
Rejection(s) not reiterated from the previous Office Action are hereby withdrawn. The following rejections are either reiterated or newly applied. They constitute the complete set of rejections presently being applied to the instant application.
Claim Rejections - 35 USC § 103
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 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.
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 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over Chiang et al. (US 2018/0110731A1; Apr. 26, 2018) in view of Chung et al. (WO2018084806A1; May 11, 2018) and Hasegawa et al. (Clinical and Experimental immunology, 2012, 167:269-274).
Chiang throughout the reference teaches hydrogel compositions and drug delivery systems. Particularly, in example 32, Chiang discloses a composition comprising zinc, polyglutamic acid and histidine along with Herceptin and polyethylene glycol. (see: example 32; Para 0109-0110). Chiang also teaches using the composition against breast cancer (Para 0173 and 0180). While Chiang does not expressly state a complex formed of zinc, polyglutamic acid and histidine, however, upon mixing the zinc, polyglutamic acid and histidine as taught in example 32, zinc would inherently bind to the polyglutamic acid (e.g., with the amine group or carboxyl group of polyglutamic acid) and histidine (e.g., with the amine group of histidine).
Chiang does not disclose the amounts of polygama glutamic acid, zinc and histidine which read on the instantly claimed amounts. However, Chung and Hasegawa cure these deficiencies.
Chung also teaches the use of zinc and polygama glutamic acid complex for treating cancer (Abstract; Claims). Chung discloses the amount of zinc being 110 mg and the amount of polygama glutamic acid being 110 mg in the composition (Example 11; Table 2). This reads on the instantly claimed amount wherein the zinc is 50 parts and polygama glutamic acid is 50 parts (i.e., 1:1 ratio).
Hasegawa teaches that some amino acids exhibit anti-inflammatory effects and particularly teaches histidine providing anti-inflammatory effect. (Summary; Discussion).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to combine the teachings of Chiang, Chung and Hasegawa and include zinc and polygama glutamic acid in the amount disclosed by Chung. One would have been motivated to do so because both Chung and Chiang teach using these two ingredients for treating cancer and thus it would have been obvious to one skilled in the art to utilized the amount known to be effective for treating cancer and/or manipulate the amount during routine optimization to include the amount which yields optimal results. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here 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).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to combine the teachings of Chiang, Chung and Hasegawa and include histidine in an amount which would provide optimal anti-inflammatory effect as taught by Hasegawa. As discussed above, Chiang teaches the composition comprising zinc/histidine/polyglutamic acid is used as an anti-cancer product and inflammation is a known cause of cancer. Thus, it would have been obvious to one skilled in the art to manipulate the amount of histidine during routine experimentation achieve optimal anti-inflammatory amount for the patient. Further, Chiang in example 32 teaches using histidine as a buffer solution and it would have been obvious to find optimal amount during routine optimization based on the desired pH.
From the combined teaching of the cited references, one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Response to Arguments
Applicant argued that the 0.5M histidine solution used in Chiang is merely a buffer and nothing in Chiang provides any reason to include it as an essential active component.
In response, firstly it is argued that the instant claims do not recite the histidine is included as an essential active component. Even in the case the claims recite histidine is included as an essential active component, Chiang teaches the composition comprising histidine and the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977).” MPEP § 2112, I.
Applicant argued that although Hasegawa discloses that histidine exhibits anti-inflammatory effect, nothing in Hasegawa teaches or suggest cancer application in any way. The examiner asserted that inflammation is known to be a cause of cancer such that it would be obvious to relate histidine's anti-inflammatory effect and determine an amount of histidine to achieve an optimal anti-inflammatory effect in a patient. Applicant assert that this reasoning is not valid because reference 1 and 2 provided in the remarks provide evidence that anti-inflammatory effects do not directly translate into anticancer therapeutic effects. It was argued that as such, the claimed ratio of zinc, polyglutamic acid and histidine is not taught or rendered obvious.
In response, the examiner argues that reference 1 (Immunity, Inflammation, and Cancer) throughout teaches inflammation being a well established cause of cancer. Reference 1 discloses the present of leukocytes within tumors … provided the first indication of a possible link between inflammation and cancer. Yet, it is only during the last decade that clear evidence has been obtained that inflammation plays a critical role in tumorigenesis. A role for inflammation in tumorigenesis is now generally accepted and it is an essential component of all tumors Inflammation can affect every aspect of tumor development and progression as well as the response to therapy. A combination of anti-inflammatory approaches that target tumor is also taught. (Introduction; Conclusion; Entire Document). Reference 1 throughout discusses inflammation being a cause for cancer and anti-inflammatory therapy is taught to target cancer/tumor cells. Therefore, applicant’s argument regarding the reference 1 teaching otherwise does not seem persuasive as the reference clearly recommends anti-inflammatory therapy for cancer/tumor treatment.
Regarding reference 2, which uses canakinumab (anti-inflammatory agent) as adjuvant therapy, the reference discloses that the study did not show a disease free survival benefit of adding canakinumab. However, this does not mean that the anti-inflammatory drug did not reduce the symptoms of disease or reduced the size of the tumor, etc. Just because the anti-inflammatory drug did not show a disease free survival, it does not mean that the drug did not have any beneficial impact such as reduction in symptoms of disease, etc.
Further, Leonardi et al. (Immunity & ageing, January 19, 2018, 15:1) teaches inflammation is a hallmark of cancer and is widely recognized to influence all cancer stages from cell transformation to metastasis. Thus, it was well known that inflammation causes cancer/tumor growth and anti-inflammatory therapy would be beneficial in treating cancer patients. As such, since Chung describes zinc and polyglutamic acid in a 1:1 ratio (e.g., 50 part to 50 part) and Hasegawa teaches histidine exhibits anti-inflammatory effect, it would be obvious to relate histidine's anti-inflammatory effect and determine an amount of histidine to achieve an optimal anti-inflammatory effect in a patient.
Applicant argued of superior anticancer activity with regards to the concentration of zinc which is 15% or greater. Particularly, applicant referred to example 1 and comparative example 1 for argument of unexpected results.
In response, firstly it is argued that comparative example 1 (Alex 1) comprises zinc histidine complex and inventive example 1 (Alex 2) comprises zinc, histidine and polyglutamic acid complex. The variable in these examples is polyglutamic acid and it appears the examples show the polyglutamic acid provides anticancer effects. However, as discussed in the rejections above, Chiang and Chung disclose polyglutamic acid provides anticancer effects. Thus, it does not appear that the anticancer effects of polyglutamic acid are unexpected since the prior art already teaches such effects. Further, if these examples in the specification are meant to show criticality of the amount of zinc, the examiner argues that both examples should comprise the same ingredients with the only variable being the concentration of the zinc ingredient to properly show the criticality of the amount of zinc. In the examples disclose, the comparative examples does not comprise polyglutamic acid and thus it is not a proper comparison to determine the criticality of the concentration of zinc.
Further, figures 1-5 disclose concentrations ranging from 0-300 microgram/ml. It is unclear whether these concentrations are referring to the concentrations of the zinc component in the complex and how these amounts translate into zinc having a concentration of 15% or higher. The examiner requests the applicant provide clarity on how the examples and figures 1-5 show the zinc having a concentration of 15% or greater.
Additionally, while the figures (1-3) provided in the specification do show there being a difference between the inventive and comparative examples in terms of cell viability, the difference is generally no more than 15-20%, and applicant have not shown how this difference is of statistical and practical significance. Particularly, as discussed above, the prior art teaches polyglutamic acid having anticancer properties and thus, this difference in cell viability of cancer cells does not appear to be unexpected.
Applicant also argued that the claimed invention has the effect of increasing water solubility by adding histidine to increase the absorption rate in the body.
In response, as discussed supra, the examiner reiterates that Chiang discloses a composition comprising zinc, polyglutamic acid and histidine. Therefore, applicant’s argument that the addition of histidine increases water solubility and absorption rate in the body is not persuasive to overcome the rejection because the prior art explicitly teaches a combination which comprises all three of the claimed components, including histidine.
Conclusion
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.
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/A.S/Examiner, Art Unit 1616
/SUE X LIU/Supervisory Patent Examiner, Art Unit 1616