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 .
Election/Restrictions
Applicant's election with traverse of Group II, drawn to a method of providing information to predict the proliferative ability of stem cells in the reply filed on October 8, 2025 is acknowledged. The traversal is on the grounds that the searches are coextensive and therefore lack search burden and that the examiner did not provide reasons or examples to support the lack of patentable distinction. Applicant’s traversal also asserts that the examiner has indicated Groups I-IV lack a same or corresponding technical feature and has not indicated that the content of the claims were interpreted in light of the description in making the assertion of a lack of unity of invention and therefore has not met the necessary burden to support the assertion.
With regard to search burden, Applicant’s traversal is not found persuasive because search burden is only a consideration under U.S. restriction practice. The instant application is being treated under the restriction standards of Unity of Invention which does not consider search burden. With regard to unity of invention, Applicant’s traversal is not found persuasive as the examiner has indicated that Groups I-IV do share the special technical feature of “developmental arteries and neural crest epidermal growth factor-like (DANCE) expression as it relates to stem cell proliferation” which is supported by Pg. 2 of Applicant’s specification regarding the nature of the invention which states:
“Under the circumstances, the present inventors have made diligent efforts to develop a technology capable of improving the proliferative ability of stem cells, and as a result, confirmed a significant relationship between the DANCE gene and the proliferative ability of a mesenchymal stem cell, thereby completing the present application.”
However, the examiner was able to provide art which indicated that the role of DANCE/Fibulin-5 as being important for stem cell proliferation is known in the art, thereby demonstrating that the special technical feature shared by the groups lacks novelty. Therefore, a lack of unity exists between the restricted groups.
The requirement is still deemed proper and is therefore made FINAL.
Status of the Claims
Claims 1-15 are pending. Claims 1-7 and 11-15 have been withdrawn. Claims 8-10 are examined on the merits.
Priority
The instant application was filed February 17, 2022 and is a 371 application of PCT/KR2019/015859 filed on November 19, 2019, which claims benefit to Korean application KR10-2018-0143910 filed on November 20, 2018.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on May 19, 2021 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112
Claim 8 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 8 recites the limitation "the protein" in line 5. There is insufficient antecedent basis for this limitation in the claim as there is only a prior recitation of “a DANCE protein”. Appropriate correction is required. It is recommended that Applicant amend to make clear that the protein is “the DANCE protein”.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 8-10 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
MPEP 2106.04 states:
In addition to the terms "laws of nature," "natural phenomena," and "abstract ideas," judicially recognized exceptions have been described using various other terms, including "physical phenomena," "products of nature," "scientific principles," "systems that depend on human intelligence alone," "disembodied concepts," "mental processes," and "disembodied mathematical algorithms and formulas." It should be noted that there are no bright lines between the types of exceptions, and that many of the concepts identified by the courts as exceptions can fall under several exceptions. For example, mathematical formulas are considered to be a judicial exception as they express a scientific truth, but have been labelled by the courts as both abstract ideas and laws of nature. Likewise, "products of nature" are considered to be an exception because they tie up the use of naturally occurring things, but have been labelled as both laws of nature and natural phenomena. Thus, it is sufficient for this analysis for the examiner to identify that the claimed concept (the specific claim limitation(s) that the examiner believes may recite an exception) aligns with at least one judicial exception.
Claim 8 recites a method of providing information to predict the proliferative ability of stem cells and claims 9 and 10 depend from claim 8. Claims 8-10 are drawn to the statutory category of a process and are eligible under Step 1.
Claim 8 recites “comparing the measured expression level with that of the DANCE gene of a control group” in lines 8-9. The broadest reasonable interpretation of “comparing” includes observation and decision-making. Thus, claim 8 recites a concept that falls into the mental processes group of abstract ideas.
Claim 9 recites “determining that the stem cells have high proliferative ability when the expression level…is higher than that of the control group.” Thus the determining step is performed via comparison between two groups which results in the decision of on measurement being higher than another and therefore recites a concept that falls into the mental processes group of abstract ideas.
Claim 10 which depends from claim 8 is similarly rejected as incorporating the limitations of a rejected claim while failing to correct the deficiency.
Thus, claims 8-10 are drawn to the judicial exception of abstract ideas under Step 2A, Prong One.
This judicial exception is not integrated into a practical application because the additional method steps are no more than insignificant extra-solution activity. Claim 8 recites additional steps of contacting stem cells with a DANCE protein or substance that binds to mRNA to form a complex encoding the protein and measuring a level of the complex to measure level of the DANCE gene. Claim 10 provides additional limitations regarding the step of measuring a level of the complex. These method steps are performed in order to generate the conditions required for use of the recited judicial exception of comparing the measured expression level and determining high proliferative ability of stem cells when the measured expression level is higher than a control group. Thus, the judicial exceptions are not integrated into a practical application under Step 2A, Prong Two.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception under Step 2B because the instant disclosure teaches well-understood, routine, and conventional methods which are implemented for the steps of contacting the stem cells with a DANCE protein or a substance that binds to mRNA encoding the protein to form a complex and measuring the level of the complex via techniques which would be well known to one having ordinary skill in the art, including using RT-PCR, competitive RT-PCR, real-time RT-PCR, RNase protection assay (RPA), Northern blotting, nucleic acid microarray including DNA, Western blotting, enzyme linked immunosorbent assay (ELISA), radioimmunoassay (RIA), radioimmunodiffusion, ouchterlony immune diffusion, rocket immunity electrophoresis, tissue immunostaining, immunoprecipitation assay, complement fixation assay, FACS, mass spectrometry, magnetic bead-antibody immunoprecipitation, protein chip, or a combination thereof. MPEP 2106.03(d)(II) states:
The courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity:
ii. Using polymerase chain reaction to amplify and detect DNA, Genetic Techs. Ltd. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1377, 115 USPQ2d 1152, 1157 (Fed. Cir. 2015);
iii. Detecting DNA or enzymes in a sample, Sequenom, 788 F.3d at 1377-78, 115 USPQ2d at 1157); Cleveland Clinic Foundation 859 F.3d at 1362, 123 USPQ2d at 1088 (Fed. Cir. 2017);
vii. Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014);
viii. Hybridizing a gene probe, Ambry Genetics, 774 F.3d at 764, 113 USPQ2d at 1247.
Thus, the additional elements recited in the claims are no more than well-understood, routine, and conventional activities commonly known in the art under Step 2B.
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.
Claims 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over Schiemann and Lodish (US 2004/0126788 A1) and Feng et al. (2013 CD133+ subpopulation of the HT1080 human fibrosarcoma cell line exhibits cancer stem-like characteristics. Oncology reports, 30(2), 815-823, hereafter “Feng”).
With regard to claims 8 and 9, Schiemann and Lodish teach a method for assessing the tumorigenicity of cancer cells comprising detecting the level of expression or activity of fibulin-5, also known as DANCE (Para. [0005], line 3) in a test sample of cells and comparing the level of expression or activity of fibulin-5 in the test sample to a baseline level of fibulin-5 from a control sample of cells (Para. [0007], lines 2-7, see also claims 1-3). Schiemann and Lodish teach wherein the means for detecting fibulin-5 expression can include a hybridization probe which hybridizes to a nucleic acid molecule encoding fibulin-5 (Para. [0014], lines 3-12), which is considered to reasonably read on a substance that binds to mRNA encoding the protein, and wherein the means for detecting the activity of fibulin-5 can be measuring proliferation of cells and detecting DNA synthesis (Para. [0008], lines 18-20), which is an indicator of cell proliferation. Additionally, Schiemann and Lodish teach wherein detection of a statistically significant difference in fibulin-5 expression or activity in the test sample compared to the control sample is indicative of a difference in tumorigenicity (Para. [0007], lines 7-12), this is considered to reasonably read on the instantly claimed steps of measuring and comparing expression levels of fibulin-5. Further, Schiemann and Lodish teach wherein the method can be used to predict cells which are likely to be tumorigenic based on fibulin-5 expression (Para. [0011], lines 21-23) and wherein “tumorigenicity” refers to a change of a cell or cell population which involves cellular proliferation (Para. [0055], lines 2 and 6-8), thus providing support for use of the method to predict cellular proliferation.
While Schiemann and Lodish teach use of this method for predicting the proliferative ability of cancer cells such as human fibrosarcoma HT1080 cancer cells (Example 3), they do not teach use of this method specifically for fibrosarcoma cancer stem cells.
Nevertheless, it was well known that the HT1080 cancer cell line comprises cancer stem cells as evidenced by Feng (Abstract).
Accordingly, it would have been obvious to practice the method of Schiemann and Lodish to predict the proliferative ability of fibrosarcoma HT1080 cancer cells and choose CD133+ fibrosarcoma cancer stem cells with a reasonable expectation of success. One of ordinary skill would have been motivated to do so because cancer stem cells are an obvious subtype of the fibrosarcoma HT1080 cancer cells, and Feng teaches cancer stem cells have properties of self-renewal and multilineage differentiation capacity and provide the initiating cells from which tumors are derived and sustained (Abstract), which is clinically relevant to staging and treating fibrosarcoma.
Furthermore, in regard to claim 9, “FBLN-5-expressing HT1080 cells exhibited a trend towards enhanced DNA synthesis as compared to controls” [0219], thereby establishing cells having a high proliferative ability when the expression of the filbulin-5 gene is higher than that of the control group. Although, Schiemann and Lodish in view of Feng do not determine that the CD133+ cancer stem cells have a higher proliferative ability when the expression level of the fibulin-5 gene is higher than control, since CD133+ cancer stem cells are a subpopulation of HT1080 cells, it would be obvious to make this determination. Note that the determining step of claim 9 does not necessarily require that the cancer stem cells actually have a higher proliferative ability when the level of fibulin-5 expression level is measured, which is a contingent limitation of the method.
With regard to claim 10, as stated above, Schiemann and Lodish teach a hybridization probe wherein the detection can be performed by methods including but not limited to Northern blot (Para. [0008]).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERIN V PAULUS whose telephone number is (571)272-6301. The examiner can normally be reached Mon-Fri 8 AM-5 PM.
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/ERIN V PAULUS/Examiner, Art Unit 1631
/ARTHUR S LEONARD/Examiner, Art Unit 1631