DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 10 June 2026 has been entered.
Specification
The use of the term “Matrigel” throughout the specification, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Rejections - 35 USC § 103 (Maintained)
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 95-97 and 99-101 stand as rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Masur et al. 1996; in view of Belluci et al., 2007; Surban et al., 2008; and evidenced by the Millipore Matrigel® and Corning® pamphlets (all cited previously).
On pages 2-3 of Remarks filed 10 June 2026, Applicant argues that contrary to the Examiner’s position the specification need not provide evidence that the claimed element of 700 µL is “critical” in order for the invention to be non-obvious.
This is not persuasive because the applied prior art differs from the claimed invention only with respect to the amount (volume) of Matrigel®, and the Examiner has made a rejection based upon routine optimization (MPEP 2144.05(II)(A)). The Court has stated that, generally, such differences amount to mere optimization and will not support patentability unless there is evidence indicating the claimed feature is critical.
MPEP 2144.05(III) sets forth Applicant's burden for rebuttal of a prima facie case of obviousness based upon routine optimization. Applicant must provide either a showing that the particular amount or range recited within the claims is critical; and/or a showing that the prior art reference teaches away from the claimed amount.
In the instant case, Figure 13 of the specification teaches the invention comprising a range of Matrigel® volumes deposited in a 12 well plate; which yields a range of basement layer thicknesses. The disclosure states: “400 to 800 µL the thickness of the matrigel layer is in the range of 1.04 to 2.08 mm” (pg. 15). Figure 14 teaches the effects that a small volume of Matrigel (400 µl and 500 µl) have on fractal dimension (Fig. 14A) and lacunarity (Fig. 14B) relative to larger volumes of 600-800 µl, but neither of these figures provides evidence that 700 µL is critical to the composition of the claims. While the description of Figure 15 states, “the importance of using 700ul of Matrigel where the curves show a peak and the effect is maximum”, it should be noted that this is only in relation to a peak and maximal effect at 40-80h after plating, which are not claimed features of the invention. Thus, demonstration of a maximal effect is not evidence that 700 µL is critical to the material invention of the claims.
Applicant has provided no specific teaching away from this specific volume within the prior art. A 12-well plate has a standard cell growth surface area of roughly 3.8 cm² per well. Coating this area with 700 µL of Matrigel® results in a gel layer depth of approximately 1.84 mm, which is thicker and would be required for 2D cultures, and is more specifically tailored for 3D embedded cultures. However, the Corning Matrigel® reference of record states: “The optimal protein concentration is application-dependent”; and the only requirement for Corning Matrigel® matrix is that it should not be diluted to a final concentration below 4 mg/mL (see bullet 25 of Corning reference of record). The reference states: “Corning Matrigel® matrix that is diluted to a very low concentration (e.g., less than 3 mg/mL) will form a weaker or more fragile gel and is more likely to detach from tissue culture plastic” (bullet 26). The reference further states: “The higher the protein concentration the higher the viscosity. Concentrations over 13.0 mg/mL can be very thick.” But Applicant has provided no explicit teaching away in any of the prior art references.
Applicant has not traversed the findings of relevant facts, nor the underpinning reasoning of the rejection itself. The instant invention is directed to a composition and does not comprise any "procedural steps" as previously argued by Applicant.
Regarding claims 95, 99 and 101: Masur teaches >50 cells/mm³ successfully results in fibroblasts versus myofibroblasts. This cell density falls squarely within the range of the instant claim 95 (45 cells/mm³ up to 62 cells/mm³); and is the specific density required by instant claims 99 and 101 (50 cells/mm³).
Masur is silent only with respect to two elements of instant claim 95: (i) 700 µL volume of a basement membrane matrix, which is remedied by the Matrigel® pamphlet; and (ii) the specific elements that make up the basement membrane comprising Engelbreth-Holm-Swarm mouse sarcoma extract, laminin, collagen IV, heparin sulfate proteoglycans, entactin/nidogen, and growth factors, which is evidenced by the Corning pamphlet, relied upon as disclosing the specific components that make up the Matrigel®.
The Matrigel® pamphlet discloses a universal fact, which is that a volume of at least 300 µL of Matrigel® is necessary to coat the surface of a 12-well plate and at least 700 µL is needed for a 6-well plate required by the current claims (See pg. 2, last row in Table of Volumes). A 12-well plate has a standard cell growth surface area of roughly 3.8 cm² per well. Coating this area with 700 μL of Matrigel® results in a gel layer depth of approximately 1.84 mm, creating a relatively thick matrix. The Matrigel® prior art discloses thin gel coatings require 50 µL/cm2 growth area and thick gel coatings 150-200 µL/cm2 growth area, which is equivalent to 570 (3.8 cm² per well X 150 µL/cm2 growth area) to 760 µL (3.8 cm² per well X 150-200 µL/cm2 growth area) volume. Thus, the volume of the claims falls squarely within the volumes recommended by the disclosure.
The Corning Matrigel® reference further states: “The optimal protein concentration is application-dependent”; and the only requirement for Corning Matrigel® matrix is that it should not be diluted to a final concentration below 4 mg/mL (see bullet 25 of Corning reference of record). The reference states: “Corning Matrigel® matrix that is diluted to a very low concentration (e.g., less than 3 mg/mL) will form a weaker or more fragile gel and is more likely to detach from tissue culture plastic” (bullet 26). The reference further states: “The higher the protein concentration the higher the viscosity. Concentrations over 13.0 mg/mL can be very thick. The Corning Matrigel matrix products will always exhibit extreme viscosity and will not become free-flowing until diluted” (bullet 23).
A person having ordinary skill in the art would have been able to adjust the dilution volume of the Matrigel® applied to the culture well with predictable success in achieving 700 µL volume, since the growth surface area of the 12-well plate is 3.8 cm² per well and the prior art teaches 570 (3.8 cm² per well X 150 µL/cm2 growth area) to 760 µL (3.8 cm² per well X 150-200 µL/cm2 growth area) volume for thick gel coatings. Volume of Matrigel® applied to the culture well can be optimized via routine experimentation, does not require undue further experimentation on the part of the skilled artisan, and does not constitute a patentable invention over what was disclosed in the prior art. The Examiner has articulated a rationale including an explanation of why it would have been routine optimization to arrive at the claimed invention and why a person of ordinary skill in the art would have had a reasonable expectation of success to formulate the claimed amount.
Applicant traverses the requirements for a rebuttal of a prima facie case of obviousness based upon routine optimization but has failed to provide evidence that this volume is critical or that the prior art explicitly teaches away from this volume.
For all these reasons, the composition invention is obvious in view of the compositions disclosed in the art before the effective filing date of the application, and the rejection is maintained.
Conclusion
No claim is allowed.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STACEY NEE MACFARLANE whose telephone number is (571)270-3057. The examiner can normally be reached M-F 7:30-5 (EST) & Sat. A.M..
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/STACEY N MACFARLANE/Examiner, Art Unit 1675
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