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 .1
Status of Claims
Claims 7-15 and 20-22 are pending.
Election/Restrictions
Applicant’s election without traverse of the species atypical PKC (aPKC) inhibitor ζ -Stat2
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, in the reply filed on Feb 23 2026 is acknowledged. Claims 7, 9, 12 and 20-22 read upon the elected species. Claims 8, 10-11, 13-15 are withdrawn as being drawn to a nonelected species.
Information Disclosure Statement
The information disclosure statement(s) (IDSs) submitted on 7/19/2022 (total of 2) is/are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 7 is objected to because of the following informalities:
Line 1 of claim 7 recites “the susceptibility of colon cancer cells. . . ”; this is the first occurrence of the term “susceptibility,” accordingly the use of the term “the” results in this objection;
Line 3 of claim 7 recites “a subject suffering from colon cancer…”. Since lines 1-2 already introduced “a subject suffering from colon cancer”. Examiner requests that line 3 be amended to clarify whether the subject is intended to be the same. For example, line 3 may be amended to “[[a]] the subject suffering from colon cancer” or similar.
Similarly, line 9 of claim 7 recites “to an aPKC inhibitor”. Examiner recommends it recite “the aPKC inhibitor”.
Claim 7, line 9 recites the bullet point (i). Since there is only a single bullet point recited, examiner recommends removing the “(i)”.
Appropriate corrections or explanation is requested.
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.
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 7, 9 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. “High mobility group box-1 is phosphorylated by protein kinase C zeta and secreted in colon cancer cells,” Biochemical and Biophysical Research Communications 424 (2012) 321-326. Lee is cited (as NPL Ref. 26) on one of the two IDS(s) submitted by Applicant on July 19 2022.
Claim 7 is directed to a method of measuring the susceptibility of colon cancer cells of a subject suffering from colon cancer to an atypical PKC (aPKC) inhibitor, the method comprising:
obtaining a colon cancer cell sample from a subject suffering from colon cancer, wherein the colon cell sample comprises colon cancer cells;
exposing a portion of the colon cancer cells of the colon cell sample to an inhibitor of an aPKC, while leaving another portion of the colon cancer cells of the colon cell sample untreated;
detecting cell proliferation, expression, and activation of one or more aPKCs in treated and untreated cells;
selecting a subject having a cancer susceptible to an aPKC inhibitor by detecting (i) the reduction of proliferation, expression and activation of one or more aPKCs in treated cells compared to untreated cells, wherein reduction indicates the subject's cancer is susceptible to aPKC inhibitors.
Regarding claim 7 and the limitations of selecting a claimed colon cancer subject in need and detecting aPKC overexpression and activation in a subject’s cells Lee teaches a demonstration of overexpression and activation of PKC-ζ in colon cancer tissues, see abstract. Lee suggests studying colon cancer using HCT116 cell line (see Section 2.1 page 372) to suggest obtaining/sampling colon cancer cells from a subject in need.
Regarding the limitation of exposing colon cancer cells to an atypical PKC inhibitor, Lee teaches the exposure of HCT116 colon cancer cells to PKC inhibitors (GÖ6983 and rottlerin) to inhibit PKC and to decrease HMGB1 secretion See Figure 2 page 323. See also Section 3.2, Atypical PKCs bind to HMBG1 in HCT116 cells page 322.
Lee concludes that PKC-ζ phosphorylates HMGB1, and the phosphorylation of specific serine residues in the nuclear localization signal regions enhances HMGB1 secretion in colon cancer cells, see abstract.
With regard to the obtaining from colon cancer subject patients and measuring step (detecting cell proliferation, expression, and activation of one or more aPKCs in treated cells), Lee teaches the evaluation of PKC-ζ in colon cancer tumor tissue, versus adjacent normal mucosa, where specimens from 30 cancer patients with matched normal mucosae. See Section 3.4 PKC- ζ expression in tumor tissues, page 324.
Lee teaches that the most critical PKC isotype that regulates secretion of HMGB1 (a protein overexpressed and secreted in cancer cells) was PKC-ζ, which was identified by using PKC inhibitors and siRNA experiments, see abstract and page 322, Section 2.6. Further, Lee teaches that PKC- ζ is critical for HMGB1 secretion, see Section 3.3, pages 323-324. Lee identifies these PKC inhibitors (Gö6983, ATG and rotterlin) as being atypical PKC inhibitors, see Section 3.2 entitled Atypical PKC’s bind to HMGB1 in HCT116 cells.
It is noted that Lee does not expressly teach portioning a sample of colon cancer cells into some that are exposed to an aPKC inhibitor and comparing expression/activation of aPKC in the two samples. However, such limitation would be routinely optimized by a person having ordinary skill in the art (PHOSITA), where levels of aPKC are noted to be measured by levels of HMGB1 secretion pre and post levels of exposure. A PHOSITA would routinely optimize to use controls of non-exposed tumor cells obtained from the same tumor sample, where Lee teaches exposure cells to an aPKC inhibitor to measure its effects in terms of PKC expression and activation as measured by HMGB1 secretion before and after exposure.
Prior to the filing of the instant application a PHOSITA following the teachings of Lee would have found it prima facie obvious to arrive at the claimed invention’s method, where Lee teaches sampled colon tumor cells, as well as using a colon cell model, exposed these cells to aPKC inhibitors and took measure of aPKC expression and activation before and after exposure as well as comparing them to an unexposed control, where it would be routine to use and substitute an unexposed control sample, versus the same cells measured for aPKC activation pre-exposure. See MPEP 2143(b) noting [s]imple substitution of one known element for another to obtain predictable results (substituting pre-PKC inhibitor exposure colon cancer cells, as a control, with non-exposed colon cancer cells, as a control, to measure levels of aPKC expression and activation due to aPKC inhibitor exposure.
Regarding claim 9 where one or more aPKC comprises PKC- ζ, Lee teaches a demonstration of overexpression and activation of PKC-ζ in colon cancer tissues, see abstract.
Regarding claim 12 directed to the increased phosphorylation of PKC- ζ, Lee concludes that PKC- ζ is involved in the phosphorylation of HMGB1, and the phosphorylation of specific serine residues in the nuclear localization signal regions is related to enhanced HMGB1 secretion in colon cancer cells, see abstract.
Claims 7, 9, 12 and 20-22 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. High mobility group box-1 is phosphorylated by protein kinase C zeta and secreted in colon cancer cells Biochemical and Biophysical Research Communications 424 (2012) 321-326 in view of US Pub 2017/0348336 A1, claiming priority to June 2, 2016. US Pub ‘336 is cited on the PTO-892 form.
While claims 7, 9 and 12 disclose the claimed method of measuring the susceptibility of colon cancer cells of a subject suffering from colon cancer to an atypical PKC (aPKC) inhibitor, it does not teach the particular atypical PKC (aPKC) inhibitor ζ -Stat as recited in claims 20-21.
To correct this deficiency regarding claims 20-21, US Pub '336 teaches the treatment of a cancer (melanoma) in a subject in need thereof, the method comprising administering a therapeutically effective amount of an inhibitor of an atypical protein kinase C (aPKC), see claim 1.
US Pub '336 teaches the particular expression of PKC- ζ (aka PKC zeta) in cancer (melanoma), see paragraph 15.
US Pub '336 teaches in particular, applicant's elected species of atypical PKC inhibitor, ζ -Stat is a preferred embodiment, see paragraph 35 and claims 9 and 18.
Prior to the filing of the present patent application, it would have been prima facie obvious to a PHOSITA following the teachings of Lee to arrive at the claimed invention’s method, where Lee teaches sample colon tumor cells, as well as using a colon cell model, exposed them to aPKC inhibitors and took measure of aPKC expression and activation before and after exposure (equivalent to a control versus exposed cell), where US Pub ‘336 teaches the particular elected species of aPKC inhibitor, ζ -Stat as detailed above.
Regarding claim 22 reciting further treating the subject with surgery, radiation therapy, or immunotherapy, US Pub ‘336 teaches its PKC inhibitor, may be administered with a surgery, a radiation therapy, an immunotherapy or a combination thereof. See paragraph 120.
Conclusion and Correspondence
No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to WILLIAM LEE whose telephone number is (571)270-3876. The examiner can normally be reached M-F.
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, Adam C. Milligan can be reached at (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/WILLIAM Y LEE/Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
1 CONTINUING DATA
This application is a DIV of 15/643,117 07/06/2017 PAT 11337944
15/643,117 has PRO 62/359,496 07/07/2016
2 CAS Reg. No. 3316-02-7
8-Hydroxy-1,3,6-naphthalenetrisulfonic acid.