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 I (claims 1 and 6) in the reply filed on 10/08/2025 is acknowledged. The traversal is on the ground(s) that Groups II and III are directed to processes of using the product of Group I. Applicant also argues that the unity of invention is the issue at hand and that restriction of the claims at this stage would deny Applicant the opportunity to argue on the merits during prosecution as to novelty or inventive step. Applicant argues that the claims as amended define a contribution over the prior art and should be examined in the same application because the Sachs reference does not teach the amendments to claim 1. This is not found persuasive because the technical feature under consideration when the Restriction requirement was made was a medium containing amphiregulin, which was disclosed by Sachs. Thus, the claim was found to lack a special technical feature distinguished over the prior art. Hence, the requirement is still deemed proper and is therefore made FINAL, as Applicant cannot amend the claim to overcome initial grounds upon which a lack of unity of invention was made and supported.
Claims 7-10 and 19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 10/08/2025.
Claims 1, 6-10, and 19 are pending and claims 1 and 6 have been examined herein.
Priority
The instant claims herein are examined utilizing the accepted effective filing date of 11/08/2019 for the basis of any prior art rejections.
Drawings
The drawings are objected to because Fig. 4A-C and 9A-D are illegible. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities:
The specification’s description of the figures does not contain the description for the sub-figures (ex. 1A, etc.).
Appropriate correction is required.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 recites multiple instances of “A8301”, which should be written as “A83-01”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1 and 6 are 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 1 contains the trademark/trade name neuregulin. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a recombinant protein used, for example, as a therapeutic pharmaceutical in the treatment of nervous system or muscular system diseases and, accordingly, the identification/description is indefinite.
Please note that claim 6 is included in this rejection for its dependency on indefinite claim 1.
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.
Claim(s) 1 and 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dang et al (CN108624561B, 5/26/2018; published 10/9/2018) in view of Baillo et al (J Cell Physiol. 2011 Oct;226(10):2691-701), Robins et al (US8153429B2, 2/23/2007; published 4/10/2012), Zhang et al (Cell Rep. 2018 Oct 16;25(3):598-610.e5), and Pavlovich et al (Exp Cell Res. 2011 Apr 1;317(13):1872-84).
Dang teaches a primary tumor cell culture medium for culturing epithelial cells containing hydrocortisone, EGF, Insulin, ROCK inhibitors, where the insulin is at 2.5 to 7.5 micrograms/mL, and the ROCK inhibitor is Y27632 in an amount of 5-15 micromolar (see claim 1 of Dang) (“A primary cell culture medium . . ., the medium comprising . . ., epidermal growth factor, insulin, . . . , ROCK kinase inhibitor Y27632, . . . ; the content of insulin is 1 ug/ml to 10 ug/ml, . . . ; the content of Y27632 is 5 uM to 15 uM,” as in instant claim 1 in part).
Dang differs from the instant invention in that it does not teach that the medium contains amphiregulin (10 ng/ml to 100 ng/ml), B27, Neuregulin 1 (5 nM to 20 nM), fibroblast growth factor 7 (2.5 ng/ml to 20 ng/ml), A8301 (100 nM to 500 nM), and P38/MAPK inhibitor SB202190 (100 nM to 500 nM), the content of epidermal growth factor is 2.5 ng/ml to 20 ng/ml, or B27 is diluted with a final concentration of 1:25 to 1:100 (claim 1 in-part).
Baillo teaches culture of mammary epithelial cells, specifically a serum-free base medium for MCF10A and MCF10A + AREG cells was SFIH (Ham's F-12 with 1 µg/ml hydrocortisone, 1 mg/ml bovine serum albumin, 10 mm HEPES, 5 mm ethanolamine, 5 µg/ml transferrin, 10 nm triiodothyronine, 50 nm sodium selenate, 5 µg/ml gentamicin, 2.5 µg/ml fungizone, and 5 µg/ml insulin), and MCF10A cells required 10 ng/ml EGF (SFIHE). MCF10A + AREG cells were MCF10A cells grown in SFIH medium with 20 ng/ml exogenous AREG (Materials and Methods, para 2) (“10 to 100 ng/ml amphiregulin . . . EGF is 2.5 ng/ml to 20 ng/ml” as in instant claim 1 in-part; “wherein the primary breast epithelial cells are breast tumor cells” as in instant claim 6). The reference further teaches serum-free mammary epithelial growth medium supplemented with B27, 1 µg/ml hydrocortisone, 5 µg/ml insulin, 5 µg/ml β-mercaptoethanol, and 10 ng/ml EGF (In vitro mammosphere assay, para 1) (“B27” as in instant claim 1 in-part). AREG promotes proliferation of breast cancer cells through the expression of an AREG/EGFR autocrine loop (Discussion para 1).
Robins teaches a cell culture medium containing neuregulin-1 (also known as HRG-beta), which stimulating ErbB2 tyrosine kinase activity within differentiable cells. The HRG-beta is in an amount of, for example, 10 ng/mL to 50 ng/mL (see example 3 and 5; 50 ng/mL is approximately) (“neuregulin-1” as in instant claim 1 in-part). The medium containing this amount allowed the cultures to proliferate normally and the cells were able to be maintained in the defined conditions in the absence of FGF2 (see example 3). The medium can also contain FGF-7 in an amount of 0.1 ng/ml to approximately 100 ng/ml (“FGF-7” “2.5 ng/ml to 20 ng/ml” as in instant claim 1 in-part).
Zhang teaches long-term in vitro expansion of epithelial stem cells (title). The reference teaches that small molecules that inhibit TGF-β signaling (A83-01, RepSOX, GW788388, SB431542) or ROCK (SR3677, Y-27632, Thiazovivin, GSK429286) supported continuous cell proliferation at micromolar concentrations in the F medium (Figure 1A). TGF-β signaling inhibitor (0.5–2 μM A83-01) and ROCK inhibitor (5–10 μM Y-27632) synergistically promoted epithelial cell proliferation (Figures 1B and S1; 0.5 uM is approximately 500 nM) (“A83-01” and “500 nM” as instant claim 1 in-part).
Finally, Pavlovich teaches that mammary branch initiation and extension are inhibited by pathways downstream of TGF-beta (title). The reference teaches that branching of mammary epithelial cells can be replicated in culture in the absence of mesenchyme and steroid hormones by the addition of growth factors such as amphiregulin (Results, para 1; Fig. 1). The reference also teaches 100 nM of SB202190 inhibited p38 MAPK and caused branching of the mammary cell tubules (Fig. 6) (“SB202190” and “100 nM” as in instant claim 1 in-part; “normal breast epithelial cells” as in instant claim 6).
Therefore, it would have been obvious prior to the effective filing date of the instantly claimed invention to create a culture medium for epithelial tumor cells as taught by Dang, where the medium contains amphiregulin as taught by Baillo to arrive at the instantly claimed invention. One of ordinary skill would have been motivated to combine the prior art elements [culture medium of Dang with the medium components of Baillo] according to known methods with a reasonable expectation of advantageously promoting proliferation of the cancer epithelial cells as taught by the prior art. One of ordinary skill in the art would recognize that the improvements caused by the addition of amphiregulin would improve similar cultures in the same way.
It also would have been obvious prior to the effective filing date of the instantly claimed invention to create a culture medium for epithelial tumor cells as taught by Dang and Baillo, where the medium contains neuregulin and FGF-7 as taught by Robins, to arrive at the instantly claimed invention. One of ordinary skill would have been motivated to combine the prior art elements [culture medium of Dang and Baillo with the medium components of Robins] according to known methods with a reasonable expectation of advantageously allowing the cell cultures to proliferate normally and be maintained long term as taught by the prior art. One of ordinary skill in the art would recognize that the improvements caused by the addition of FGF-7 and neuregulin would improve similar cultures in the same way.
It also would have been obvious prior to the effective filing date of the instantly claimed invention to create a culture medium for epithelial tumor cells as taught by Dang, Baillo, and Robins, where the medium contains A83-01 as taught by Zhang, to arrive at the instantly claimed invention. One of ordinary skill would have been motivated to combine the prior art elements [culture medium of Dang and Baillo with the A83-01 of Zhang] according to known methods with a reasonable expectation of advantageously promoting continuous cell proliferation in combination with Y27632 as taught by the prior art. One of ordinary skill in the art would recognize that the improvements caused by the addition of A83-01 would improve similar cultures in the same way.
Finally, it would have been obvious prior to the effective filing date of the instantly claimed invention to create a culture medium for epithelial tumor cells as taught by Dang, Baillo, Robins, and Zhang where the medium contains SB202190 as taught by Pavlovich, to arrive at the instantly claimed invention. One of ordinary skill would have been motivated to combine the prior art elements [culture medium of Dang, Baillo, Robins, and Zhang with SB202190 of Pavlovich] according to known methods with a reasonable expectation of advantageously inhibiting p38 MAPK and causing branching of the mammary cell tubules as taught by the prior art. One of ordinary skill in the art would recognize that the improvements caused by the addition of SB202190 would improve similar cultures in the same way.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GILLIAN C REGLAS whose telephone number is (571)270-0320. The examiner can normally be reached M-F 7-3.
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/G.R./Examiner, Art Unit 1632
/KARA D JOHNSON/Primary Examiner, Art Unit 1632