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 .
DETAILED ACTION
Claims 1-10 are pending in the instant application.
Claim Interpretation
Regarding instant claim 8, “Rho-kinase expression” is interpreted as any of the Rho kinase (ROCK) isoforms, ROCK1 or ROCK2. Liao taught Rho kinase has two distinct isoforms ROCK1 and ROCK2 (Liao JK et al. (J Cardiovasc Pharmacol. 2007 Jul;50(1):17–24), abstract).
Claim Rejections U.S.C. §101
Claims 1-10 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception(s) (i.e., a law of nature, a natural phenomenon, and/or an abstract idea) without significantly more. Abstract ideas include mathematical concepts (including mathematical relationships, formulas, equations, and calculations), mental processes (including concepts performed in the human mind), and certain methods of organizing human activity (including managing personal behavior, relationships, or interactions between people). The rationale for this determination is explained below:
Claims 1-10 are directed to a natural phenomenon and an abstract idea because the claims recite natural phenomenon and an abstract idea (“Step 2A prong one”) and the judicial exception(s) is/are not integrated into a practical application (“Step 2A prong two”). The “natural phenomenon” is: “the level of P-selectin expression is indicative of the presence of a condition associated with aberrant epithelial cell proliferation”. The “abstract idea” is: comparing the level of P-selectin expression to a reference value, wherein a level of P-selectin that is equal to or greater than the reference value is indicative of the presence of a condition associated with aberrant epithelial cell proliferation. It is noted claim 1 step d) recites a potential treatment step; however, in step c) the method include an embodiment which would only observe the phenomenon without a treatment step following comparison between sample and reference value if the P-selectin expression is less than the reference value. Therefore, the claim would be classified as “mere data gathering” and does not integrate the judicial exception(s) into a practical application. Thus, in step c) the absence of an indication such as ---, and wherein the P-selectin expression in the sample is greater than the reference sample--- would contain a non-treatment embodiment. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception(s). A claim that focuses on judicial exception(s) can be shown to recite something “significantly more” than the judicial exception(s) by reciting a meaningful limitation beyond the judicial exceptions. However, in the instant case, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional elements (when considered both individually and as an ordered combination) are limited to well-understood, routine and conventional limitations of measuring P-selectin gene expression or protein levels (“Step 2B”). Well-understood, routine and conventional limitations are not meaningful limitations and are not enough to qualify the claimed method as reciting something “significantly more” than the judicial exception(s) (see Part I.B.1 of the interim Guidance).
MPEP 2106.05(d)(II) provides a non-limiting list of laboratory techniques recognized by courts as well-understood, routine, conventional activity. These techniques include:
i. Determining the level of a biomarker in blood by any means, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017);
Recited active steps of the claims impose no meaningful limit on the scope of the claims and are recited at a high level of generality such that substantially all methods of measuring P-selectin gene expression and protein levels would conventionally and routinely perform such steps. Further, the specification discloses the skilled person would appreciate that determining the level of P-selectin in accordance with the present disclosure may be performed using a variety of techniques known in the art (specification, page 16, paragraph 60). Exemplary embodiments of suitable methods include: A) determining the level of P-selectin gene expression via northern blots, polymerase chain reaction (PCR)-based methods, RNA sequencing (RNAseq), targeted sequencing and NanoString gene expression analysis; and B) determining the level of P-selectin protein expression via enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), western blotting and immunohistochemistry (specification, page 16, paragraph 60). These techniques are well are well-known, routine, and conventional means of measuring P-selectin gene and protein expression as evidenced by Shamay Y et al. (Sci Transl Med. 2016 Jun 29;8(345):345ra87), wherein P-selectin protein and mRNA expression is measured in cancer cells via IHC and RNAseq in Fig. 1. Here, the claims do not contain any significant additional elements or steps beyond the observation of judicial exception(s) present when performing routine and conventional methods. Further, the active method steps are conventional and routine in the art for the reasons stated above and the claims do not amount to significantly more than the judicial exception(s). Further, just as methods comprising detecting paternal DNA sequences in particular samples by PCR was identified in Ariosa v. Sequenom as "well-known, routine, and conventional" (see first paragraph on page 13 of Ariosa Diagnostics, Inc. v. Sequenom, Inc. (Fed. Cir. 2015)) even though the prior art did not demonstrate detecting said paternal DNA sequences in said particular samples by PCR, the methods measuring a changed level of P-selectin gene expression or protein expression in cells encompassed by the instant claims are well-known, routine, and conventional. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional elements (common methods of detecting expression) are routinely performed in the art to obtain data regarding expression and treat subjects. In regards to “indicative of the presence of a condition associated with aberrant epithelial cell proliferation", it is further noted that merely presenting results of a process otherwise unpatentable under 35 U.S.C. 101 is insufficient to establish eligibility under the statute. See FairWarning IP, LLC v. Iatric Sys., Inc., No. 2015-1985, 2016 WL 5899185, at *3 (Fed. Cir. Oct. 11, 2016) (claim unpatentable under 35 U.S.C. 101 despite recitation of the step: “providing notification if [an] event has occurred”). Moreover, “[w]hile preemption may signal patent ineligible subject matter, the absence of complete preemption does not demonstrate patent eligibility…." Ariosa Diagnostics, Inc., v. Sequenom, Inc., 788 F.3d 1371, 1379 (Fed. Cir. 2015), cert. denied, No. 15-1182, 2016 WL 1117246 (U.S. June 27, 2016). Further, “Groundbreaking, innovative, or even brilliant discovery does not by itself satisfy the § 101 inquiry.” Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 133 S. Ct. 2107, 2117 (2013). The claims do not recite something “significantly more” than the judicial exception(s); rather, the claims “simply inform” the natural phenomenon to one performing routine active method steps and do not amount to significantly more than the judicial exception(s).
Claims 2-10 are also rejected because they are dependents of claim 1 that narrow the scope of claimed invention to still be directed to judicial exception(s) (i.e., a law of nature, a natural phenomenon, and/or an abstract idea) without significantly more.
Claim Rejections – 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Regarding instant claim 1, the disclosure does not identify a method wherein a) a sample of epithelial cells from a subject that expresses P-selectin; and b) a reference value of P-selectin; that are equal as indicative of the presence of a condition associated with aberrant epithelial cell proliferation. Further, because the reference value is not required to be a negative control that does not express P-selectin or a positive control that overexpresses P-selectin, the method includes embodiments wherein P-selectin is not required to be expressed to be indicative of the presence of a condition associated with aberrant epithelial cell proliferation. Claims 2-10 further do not require the reference sample to expression P-selectin or be greater than a reference sample.
Scope of the claimed genus
Claim 1 claims a method for treating a condition associated with aberrant epithelial cell proliferation, the method comprising:
a) obtaining a sample of epithelial cells from a subject;
b) determining the level of P-selectin expression in the sample;
c) comparing the level of P-selectin expression to a reference value, wherein a level of P-selectin that is equal to or greater than the reference value is indicative of the presence of a condition associated with aberrant epithelial cell proliferation; and
d) treating a subject identified in step (c) as having a condition associated with aberrant epithelial cell proliferation with an effective amount of an agent that inhibits P-selectin expression and/or activity.
Summary of Species disclosed in the original specification
The instant specification provides evidence that P-selectin is expressed in corneal epithelial cells (Figs. 1-5). The specification provides no evidence of P-selectin expression in any epithelial cell other than corneal epithelial cells, and provides no working example of the inhibition of epithelial cell proliferation in any animal subject.
In Example 2, the specification presents evidence in support of a role for P-selectin in epithelial cell proliferation. Fig. 4 shows the effects of a P-selectin inhibitor on corneal epithelial cell proliferation in vitro. Figure 5 shows photomicrographs of corneal epithelial cells in primary culture, wherein Fig. 5A/B are control cultures, Fig. 5C/D are treated with Rho kinase inhibitor Y27632, and Fig. 5E/F are combination treatment of Y27632 and P-selectin siRNA. In summary, the examples have 0 species wherein a reference value that has P-selectin expression equal to a condition associated with aberrant epithelial cell proliferation as indicative of the presence of a condition associated with aberrant epithelial cell proliferation.
State of the Relevant Art
It was well-known in the prior art that P-selectin is expressed on the surface of both stimulated endothelial cells and activated platelets (Heller et al (WO 2015/161192, pages 1-2, paragraph 5). Shamay et al. (Sci Transl Med. 2016 8(345): 345ra87) taught that P-selectin was also expressed on cancer cells in many human tumors (abstract), as well as in tumor stromal cells and tumor-adjacent vasculature, but not in adjacent normal tissue (see e.g. Shamay at Fig. 1 and paragraph bridging pages 1 and 2). Both Heller and Shamay taught that drugs could be targeted to tumors by formulating them with P-selectin ligands in order to arrest the drugs in the tumor endothelium (which expresses P-selectin). See Shamay at title and abstract, and Heller at pages 3-4, paragraphs 13-14), and both Heller and Shamay demonstrated successful treatment of tumors using this approach. See Shamay at page 5, right column through page 8, left column, and Heller at pages 34-37 and paragraphs 172-179. Thus, at the time of the invention, there was evidence of P-selectin expression in activated platelets, activated endothelial cells, and epithelial tumors (carcinomas). The prior art does not teach P-selectin expression wherein the reference value is zero is indicative of a condition associated with aberrant epithelial cell proliferation.
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.
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.
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.
Claims 1-4, 6, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Zhou T et al. (Chinese Journal of Medicine 1997,77(7):530-531) and Chen J et al. (Chinese Medical Journal 1998 78(6) 437–439) and as evidenced by Zhou T et al. Translated (Chinese Journal of Medicine 1997,77(7):530-531) and Chen J et al. Translated (Chinese Medical Journal 1998 78(6) 437–439).
Zhou translation taught a method of measuring P-selectin in gastric cancer comprising:
Obtaining a sample of gastric cancer tissue that comprised gastric cancer epithelial cells;
Determining the level of P-selectin expression in the sample with immunohistochemistry; and
Comparing the level of P-selectin expression to a normal control gastric tissue, which served as a reference value using immunohistochemistry, wherein P-selectin expression was elevated in metastatic gastric cancer on the vascular endothelium and on the cell membranes of tumor cells when compared to the reference value, and thus was indicative of the presence of an epithelial cancer cells that expressed P-selectin
(page 1, Subjects and Methods 1.-3. Appendix Table). Zhou translation taught P-selectin-positive expression was significantly higher in patients with lymph node metastasis compared to those without expression and that the 5-year survival rate and mean survival time of patients with positive P-selectin expression were significantly poorer than those with negative expression (page 3, Discussion). Zhou translation taught that P-selectin receptors are expressed not only on tumor endothelial cells but also on the tumor cells themselves and that P-selectin may exert a dual-mediating effect between cancer cells and vascular endothelial cells—an interaction that evidently facilitates tumor invasion and metastasis (page 3, Discussion).
While Zhou translation taught P-selectin was expressed in gastric cancer, Zhou translation did not teach treatment with an effective amount of an agent that inhibits P-selectin activity and/or expression, but this is obvious in view of Chen.
Chen translation taught treatment of a subject with gastric cancer with an effective amount of a P-selectin monoclonal antibody which was effective at decreasing metastasis, wherein in subjects exhibiting cancer metastasis, the expression of P-selectin mRNA in gastric cancer tissues was significantly higher than: 1) subjects without metastasis; and 2) control reference gastric tissue samples of normal control subjects (abstract). Chen translation taught P-selectin and its corresponding mRNA expression are associated with tumor metastasis, and the P-selectin monoclonal antibody demonstrates an anti-metastatic effect against tumors (abstract).
Regarding instant claims 1-4, 6, and 9, it would have been obvious for a person having ordinary skill in the art to take the method of Zhou translation of measuring P-selectin in gastric cancer comprising:
Obtaining a sample of gastric cancer tissue that comprised gastric cancer epithelial cells;
Determining the level of P-selectin expression in the sample with immunohistochemistry; and
Comparing the level of P-selectin expression to a normal control gastric tissue, which served as a reference value, wherein P-selectin expression is elevated in gastric cancer on the vascular endothelium and on the cell membranes of tumor cells when compared to the reference value, and thus was indicative of the presence of an epithelial cancer cells that expressed P-selectin,
– and: 1) administer a subject with gastric cancer that expresses P-selectin with an effective amount of an anti-P-selectin monoclonal antibody, wherein the expression of P-selectin mRNA in gastric cancer tissues was significantly higher than a control reference gastric tissue samples of normal control subjects in view of Chen translation; and 2) measure P-selectin protein or mRNA gene expression of P-selectin in view of Chen translation.
This is obvious because:
Zhou translation taught: i) P-selectin-positive expression was significantly higher in patients with lymph node metastasis compared to those without expression; ii) 5-year survival rate and mean survival time of patients with positive P-selectin expression were significantly poorer than those with negative expression; and iii) P-selectin receptors are expressed not only on tumor endothelial cells but also on the tumor cells themselves and that P-selectin may exert a dual-mediating effect between cancer cells and vascular endothelial cells—an interaction that evidently facilitates tumor invasion and metastasis; and
1-2a) Chen translation taught P-selectin and its corresponding mRNA expression are associated with tumor metastasis, and the P-selectin monoclonal antibody demonstrates an anti-metastatic effect against tumors; and 1-2b) Chen translation taught in subjects exhibiting cancer metastasis, the expression of P-selectin mRNA in gastric cancer tissues was significantly higher than: i) subjects without metastasis. Thus, an anti-P-selectin is effective in cancer and mRNA can be measured to determine gene P-selectin expression.
There is a reasonable expectation of success because:
Zhou translation taught: i) P-selectin-positive expression was significantly higher in patients with lymph node metastasis compared to those without expression; ii) 5-year survival rate and mean survival time of patients with positive P-selectin expression were significantly poorer than those with negative expression; and iii) P-selectin receptors are expressed not only on tumor endothelial cells but also on the tumor cells themselves and that P-selectin may exert a dual-mediating effect between cancer cells and vascular endothelial cells—an interaction that evidently facilitates tumor invasion and metastasis; and
1-2a) Chen translation taught P-selectin and its corresponding mRNA expression are associated with tumor metastasis, and the P-selectin monoclonal antibody demonstrates an anti-metastatic effect against tumors; and 1-2b) Chen translation taught in subjects exhibiting cancer metastasis, the expression of P-selectin mRNA in gastric cancer tissues was significantly higher than: i) subjects without metastasis. Thus, an anti-P-selectin is effective in cancer and mRNA can be measured to determine gene P-selectin expression.
Thus, P-selectin is known to be expressed in cancer cells, a P-selectin antibody is known to decrease metastasis, and mRNA has been effectively used to measure P-selectin gene expression.
This would produce a method of treating a condition associated with aberrant epithelial cell proliferation, wherein the condition is gastric cancer (instant claim 9) treatment comprising:
Obtaining a sample of gastric cancer tissue that comprised gastric cancer epithelial cells;
Determining the level of P-selectin expression in the sample with immunohistochemistry for protein expression (instant claim 3) or measuring P-selectin mRNA for gene expression (instant claim 2); and
Comparing the level of P-selectin expression to a normal control gastric tissue, which served as a reference value, wherein P-selectin expression is elevated in a gastric cancer comprising epithelial tumor cells when compared to the reference value, and thus was indicative of the presence of epithelial gastric cancer cells that expressed P-selectin; and
Administering a subject identified in step (c) as having gastric cancer that expressed P-selectin with an effective amount of an anti-P-selectin monoclonal antibody (instant claim 4 and 6), which inhibits P-selectin activity (instant claim 1).
Claims 1-6, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Zhou T et al. (Chinese Journal of Medicine 1997,77(7):530-531) and Chen J et al. (Chinese Medical Journal 1998 78(6) 437–439) as applied to claims 1-4, 6, and 9 above, and further in view of WO 2007/117432 (Koch A et al.).
Zhou translation and Chen translation are described above.
Zhou does not teach: 1) using an agent of siRNA to inhibit P-selectin expression or activity, but this is obvious in view of Koch.
Koch taught treatment with P-selectin specific siRNAs effectively diminishes P-selectin and estrogen receptor positive human breast cancer tumor growth and angiogenesis (Fig. 5).
Regarding instant claim 5, it would have been obvious for a person having ordinary skill in the art to take the method of Zhou translation and Chen translation above and – 1) treat with an anti-P-selectin antibody or a P-selectin specific siRNA in view of Koch.
This is obvious because: 1) Koch taught treatment with P-selectin specific siRNAs effectively diminishes P-selectin and estrogen receptor positive human breast cancer tumor growth and angiogenesis.
There is a reasonable expectation of success because: 1) Koch taught treatment with P-selectin specific siRNAs effectively diminishes P-selectin and estrogen receptor positive human breast cancer tumor growth and angiogenesis. Thus, the siRNA would be expected to function to inhibit P-selectin expression on cancer cells.
This would produce a method of treating a condition associated with aberrant epithelial cell proliferation, wherein the condition is gastric cancer treatment comprising:
Obtaining a sample of gastric cancer tissue that comprised gastric cancer epithelial cells;
Determining the level of P-selectin expression in the sample with immunohistochemistry for protein expression or measuring P-selectin mRNA for gene expression; and
Comparing the level of P-selectin expression to a normal control gastric tissue, which served as a reference value, wherein P-selectin expression is elevated in a gastric cancer comprising epithelial tumor cells when compared to the reference value, and thus was indicative of the presence of epithelial gastric cancer cells that expressed P-selectin; and
Administering a subject identified in step (c) as having gastric cancer that expressed P-selectin with an effective amount of an anti-P-selectin monoclonal antibody or a specific P-selectin siRNA (instant claim 5), which inhibits P-selectin activity.
Claims 1-4, 6-7, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Zhou T et al. (Chinese Journal of Medicine 1997,77(7):530-531) and Chen J et al. (Chinese Medical Journal 1998 78(6) 437–439) as applied to claims 1-4, 6, and 9 above, and further in view of Wu J et al. (Bioorg Med Chem Lett 2016 26(19):4631-4636.).
Zhou translation and Chen translation are described above.
Zhou does not teach: 1) using an agent of a small molecule to inhibit P-selectin expression or activity, but this is obvious in view of Wu.
Wu taught (2-(3-(hydroxymethyl)-9H-pyrido[3,4-b]indol-1-yl)ethyl)-l-phenylalanine (HMCEF) as an effective P-selectin inhibitor in vitro and in vivo (abstract).
Regarding instant claim 7, it would have been obvious for a person having ordinary skill in the art to take the method of Zhou translation and Chen translation above and – 1) treat with an anti-P-selectin antibody or a small molecule P-selectin inhibitor in view of Wu.
This is obvious because: 1) Wu taught (2-(3-(hydroxymethyl)-9H-pyrido[3,4-b]indol-1-yl)ethyl)-l-phenylalanine (HMCEF) as an effective P-selectin inhibitor in vitro and in vivo.
There is a reasonable expectation of success because: 1) Wu taught (2-(3-(hydroxymethyl)-9H-pyrido[3,4-b]indol-1-yl)ethyl)-l-phenylalanine (HMCEF) as an effective P-selectin inhibitor in vitro and in vivo. Thus, the inhibitor would be expected to function to inhibit P-selectin on cancer cells.
This would produce a method of treating a condition associated with aberrant epithelial cell proliferation, wherein the condition is gastric cancer treatment comprising:
Obtaining a sample of gastric cancer tissue that comprised gastric cancer epithelial cells;
Determining the level of P-selectin expression in the sample with immunohistochemistry for protein expression or measuring P-selectin mRNA for gene expression; and
Comparing the level of P-selectin expression to a normal control gastric tissue, which served as a reference value, wherein P-selectin expression is elevated in a gastric cancer comprising epithelial tumor cells when compared to the reference value, and thus was indicative of the presence of epithelial gastric cancer cells that expressed P-selectin; and
Administering a subject identified in step (c) as having gastric cancer that expressed P-selectin with an effective amount of an anti-P-selectin monoclonal antibody or a P-selectin small molecule inhibitor of (2-(3-(hydroxymethyl)-9H-pyrido[3,4-b]indol-1-yl)ethyl)-l-phenylalanine (HMCEF) (instant claim 7), which inhibits P-selectin activity.
Claims 1, 3-4, 6, and 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over Zhou T et al. (Chinese Journal of Medicine 1997,77(7):530-531) and Chen J et al. (Chinese Medical Journal 1998 78(6) 437–439) as applied to claims 1-4, 6, and 9 above, and further in view of Shamay Y et al. (Sci Trans Med 2016 8(345) 345ra87 1-13).
Zhou translation and Chen translation are described above.
Zhou does not teach: 1) P-selectin expression in lung cancer, but this is obvious in view of Shamay.
Shamay taught overexpression of P-selectin mRNA and protein lung cancer cells (Fig. 1A-C).
Regarding instant claim 10, it would have been obvious for a person having ordinary skill in the art to take the method of Zhou translation and Chen translation above and – 1) treat gastric cancer or lung cancer that had P-selectin expression and use a normal lung cancer sample as a reference for lung cancer in view of Shamay.
This is obvious because: 1) Shamay taught overexpression of P-selectin mRNA and protein lung cancer cells.
There is a reasonable expectation of success because: 1) Shamay taught overexpression of P-selectin mRNA and protein lung cancer cells. Thus, lung cancer that expressed P-selectin would also be expected to have increased metastasis.
This would produce a method of treating a condition associated with aberrant epithelial cell proliferation, wherein the condition is gastric cancer or lung cancer (instant claim 10) treatment comprising:
Obtaining a sample of gastric or lung cancer tissue that comprised gastric cancer epithelial cells;
Determining the level of P-selectin expression in the sample with immunohistochemistry for protein expression or measuring P-selectin mRNA for gene expression; and
Comparing the level of P-selectin expression to a normal control gastric or lung tissue, which served as a reference value, wherein P-selectin expression is elevated in a gastric or lung cancer comprising epithelial tumor cells when compared to the reference value, and thus was indicative of the presence of epithelial gastric or lung cancer cells that expressed P-selectin; and
Administering a subject identified in step (c) as having gastric or lung cancer that expressed P-selectin with an effective amount of an anti-P-selectin monoclonal antibody, which inhibits P-selectin activity.
Claims 1, 3-4, 6, and 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Zhou T et al. (Chinese Journal of Medicine 1997,77(7):530-531) and Chen J et al. (Chinese Medical Journal 1998 78(6) 437–439) as applied to claims 1-4, 6, and 9 above, and further in view of Sebastiano M et al. (Blood 2017 129(7) 883-895), Shen W et al. (J Cancer Res Clin Oncol. 2014 Mar 8;140(6):1003–1009.), and Iwamura T et al. (Cancer Res (1997) 57 (6): 1206–1212.).
Zhou translation and Chen translation are described above.
Zhou does not teach: 1) administering an effective amount of a second agent that inhibits Rho-kinase, but this is obvious in view of Sebastiano, Shen, and Iwamura.
Sebastiano taught treatment with a selective Rho-kinase inhibitor GSK429286 decreased PCD62 (P-selectin) expression induced by MMP-2 (Fig. 5F).
Shen taught MMP-2 overexpression was significantly correlated with poor OS of gastric cancer patients, later TNM stage, depth of invasion, lymph node metastasis, and distant metastasis (abstract).
Iwamura taught cancer cells express P-selectin mRNA and protein and P-selectin surface expression is increased by exposure of the tumor cells to thrombin, oxygen radicals, and trypsin, suggesting that common cellular mechanisms for regulating P-selectin surface expression exist among platelets, endothelial cells, and these tumor cells (abstract).
Regarding instant claim 8, it would have been obvious for a person having ordinary skill in the art to take the method of Zhou translation and Chen translation above and – 1) administering an effective amount of a second agent that inhibits Rho-kinase in view of Sebastiano, Shen, and Iwamura.
This is obvious because: 1a) Sebastiano taught treatment with a selective Rho-kinase inhibitor GSK429286 decreased PCD62 (P-selectin) expression induced by MMP-2; 1b) Shen taught MMP-2 overexpression was significantly correlated with poor OS of gastric cancer patients, later TNM stage, depth of invasion, lymph node metastasis, and distant metastasis; and 1c) Iwamura taught cancer cells express P-selectin mRNA and protein and P-selectin surface expression is increased by exposure of the tumor cells to thrombin, oxygen radicals, and trypsin, suggesting that common cellular mechanisms for regulating P-selectin surface expression exist among platelets, endothelial cells, and these tumor cells. Thus, 1) P-selectin (PCD62) is known to be induced by MMP-2 expression and blocked with the selective Rho-kinase inhibitor GSK429286; 2) the induction protein MMP-2 is known to be expressed in gastric cancer and support metastasis; and 3) common cellular mechanisms for regulating P-selectin surface expression are known to exist among platelets, endothelial cells, and these tumor cells.
There is a reasonable expectation of success because: 1a) Sebastiano taught treatment with a selective Rho-kinase inhibitor GSK429286 decreased PCD62 (P-selectin) expression induced by MMP-2; 1b) Shen taught MMP-2 overexpression was significantly correlated with poor OS of gastric cancer patients, later TNM stage, depth of invasion, lymph node metastasis, and distant metastasis; and 1c) Iwamura taught cancer cells express P-selectin mRNA and protein and P-selectin surface expression is increased by exposure of the tumor cells to thrombin, oxygen radicals, and trypsin, suggesting that common cellular mechanisms for regulating P-selectin surface expression exist among platelets, endothelial cells, and these tumor cells. Thus, 1) P-selectin (PCD62) is known to be induced by MMP-2 expression and blocked with the selective Rho-kinase inhibitor GSK429286; 2) the induction protein MMP-2 is known to be expressed in gastric cancer and support metastasis; and 3) common cellular mechanisms for regulating P-selectin surface expression are known to exist among platelets, endothelial cells, and these tumor cells.
This would produce a method of treating a condition associated with aberrant epithelial cell proliferation, wherein the condition is gastric cancer treatment comprising:
Obtaining a sample of gastric cancer tissue that comprised gastric cancer epithelial cells;
Determining the level of P-selectin expression in the sample with immunohistochemistry for protein expression or measuring P-selectin mRNA for gene expression; and
Comparing the level of P-selectin expression to a normal control gastric tissue, which served as a reference value, wherein P-selectin expression is elevated in a gastric cancer comprising epithelial tumor cells when compared to the reference value, and thus was indicative of the presence of epithelial gastric cancer cells that expressed P-selectin; and
Administering a subject identified in step (c) as having gastric cancer that expressed P-selectin with an effective amount of i) a selective Rho-kinase inhibitor GSK429286 which inhibits Rho-kinase activity (instant claim 8); and ii) an anti-P-selectin monoclonal antibody or a specific P-selectin siRNA, which inhibits P-selectin activity.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 1-9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 11,879,012. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding instant claims 1-9, patented claim 1 teaches a method for treating a condition associated with aberrant keratinocyte epithelial cell proliferation, the method comprising:
a) obtaining a sample of keratinocyte epithelial cells from a subject;
b) determining the level of P-selectin expression in the sample;
c) comparing the level of P-selectin expression to a reference value, wherein a level of P-selectin that is equal to or greater than the reference value is indicative of the presence of a condition associated with aberrant keratinocyte epithelial cell proliferation; and
d) treating a subject identified in step c) as having a condition associated with aberrant keratinocyte epithelial cell proliferation with an effective amount of an agent that inhibits P-selectin expression and/or activity,
which is a species of the genus of instant claim 1, wherein patented claims 2-8 further overlap with instant claims 2-9, wherein:
patented claim 2 taught, wherein step (b) comprises determining the level of P-selectin gene expression in the sample (instant claim 2);
patented claim 3 taught, wherein step (b) comprises determining the level of P-selectin protein in the sample (instant claim 3);
patented claim 4 taught, wherein the agent is selected from:
i) an inhibitor of P-selectin gene expression selected from the group consisting of selected from the group consisting of mediators of RNA interference, ribozymes and CRISPR RNAs used in combination with Cas or other nucleases; and
ii) an antagonist of P-selectin activity selected from the group consisting of selected from the group consisting of an anti-P-selectin antibody or antigen binding fragment thereof, ligand mimetics for P-selectin, P-selectin blockers and small molecule inhibitors of P-selectin activity (instant claims 4-7);
patented claim 5 taught, wherein the agent is a siRNA (instant claim 4-5);
patented claim 6 taught, wherein the agent is an anti-P-selectin antibody or an antigen-binding fragment thereof (instant claim 4 and 6);
patented claim 7 taught, further comprising administering an effective amount of a second agent that inhibits Rho-kinase expression and/or activity to the subject (instant claim 8); and
patented claim 8 taught, wherein the condition associated with aberrant keratinocyte epithelial cell proliferation is cancer (instant claim 9).
Claims 1-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 11,879,012 in view of Shamay Y et al. (Sci Trans Med 2016 8(345) 345ra87 1-13).
The claims of the ‘012 patent teach the limitations of claims 1-9 for the reasons set forth above.
‘012 is described above.
‘012 does not describe the cancer as lung cancer, but treatment of lung cancer is obvious in view of Shamay.
Shamay taught overexpression of P-selectin mRNA and protein lung cancer cells (Fig. 1A-C).
Regarding instant claim 10, it would have been obvious for a person having ordinary skill in the art to take the method of patented claims 1 and 8 of a method for treating a condition associated with aberrant keratinocyte epithelial cell proliferation, the method comprising:
a) obtaining a sample of keratinocyte epithelial cells from a subject;
b) determining the level of P-selectin expression in the sample;
c) comparing the level of P-selectin expression to a reference value, wherein a level of P-selectin that is equal to or greater than the reference value is indicative of the presence of a condition associated with aberrant keratinocyte epithelial cell proliferation, wherein the condition associated with aberrant keratinocyte epithelial cell proliferation is cancer: and – 1) treat lung cancer that had P-selectin expression and use a normal lung cancer sample as a reference for lung cancer in view of Shamay.
This is obvious because: 1) Shamay taught overexpression of P-selectin mRNA and protein lung cancer cells.
There is a reasonable expectation of success because: 1) Shamay taught overexpression of P-selectin mRNA and protein lung cancer cells. Thus, lung cancer that expressed P-selectin would also be expected to be targeted by an agent that inhibits P-selectin.
Conclusion
Instant claims 1-10 are rejected.
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/J.J.S./Examiner, Art Unit 1643
/Karen A. Canella/Primary Examiner, Art Unit 1643
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