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 .
Claim Objections
The previous claim objections are withdrawn in light of the amendments.
Claim 14 is objected to because of the following informalities:
Regarding claim 14, in line 17, the phrase “the salts” could be “the salt” to describe the singular salt that is mentioned beforehand; it is slightly unclear whether there is more than one salt in the current wording.
Claim 14 recites the limitation “the higher concentration” in line 17. A different way to claim this limitation would be “a higher concentration”.
Claim 14 recites the limitation “the lower concentration” in line 18. A different way to claim this limitation would be “a lower concentration”.
Regarding claim 14, in line 20, the phrase “wherein the oxygen tension in a deepest region of the gel reaches oxygen tension from 150 μmol/L to 210 μmol/L in a deepest region of the gel” is redundantly phrased. It is suggested to use the phrase “wherein the oxygen tension is from 150 μmol/L to 210 μmol/L in a deepest region of the gel”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The previous 35 U.S.C. § 112(b) rejections are withdrawn in light of the amendments.
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 14 and 17 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 claim 14, the claim recites:
wherein the three-dimensional gradient substrate comprises the storage modulus G’ between 2 Pa and 3,000 Pa for shear strain frequencies from 0.1 Hz to 20 Hz
Specification support is found for some, but not all of the ranges/limitations claimed in Fig. 2 (for storage modulus and shear strain frequencies, specifically: the storage modulus G’ has unclear ranges and endpoints in the figures). In all, these figures do not show clear support for the claimed ranges, and therefore do not support the entire scope of the claims. Please see the MPEP § 2163.05(III), in part described below:
… analysis must take into account which ranges one skilled in the art would consider inherently supported by the discussion in the original disclosure.
MPEP § 2163.05(III)
Regarding the dependent claim 17, this claim is rejected for the same reason as the base claim upon which it depends.
Allowable Subject Matter
Claim 14 would be allowable if rewritten or amended to overcome the rejection(s) under 35 U.S.C. 112(a), set forth in this Office action.
Claim 17 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(a), set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter:
Regarding claim 14, the closest prior art is Marzorati (US 20120058551) (previously cited) in view of Allbritton (US 20190211296) (previously cited), Lourenço (“Bioengineering a novel 3D in vitro model of gastric mucosa for stomach permeability studies”) (previously cited), Deutsch (US 20070292837) (previously cited), and MacWilliams (“Luria Broth (LB) and Luria Agar (LA) Media and Their Uses Protocol”) (previously cited).
Regarding claim 14, Marzorati discloses a three-dimensional substrate (paragraph [0042] “2 compartments separated by a semi-permeable membrane; said membrane having an artificial mucus layer applied on the luminal site; and said module being characterized by anaerobic conditions at its luminal side and aerobic conditions at its basal side”) for microbial culture (paragraph [0044] “Caco-2 cells and/or HT29 cells”) comprising a gel with cross-linking (paragraph [0188] “a degree of polymerization” and in-depth discussion at paragraph [0006] for mucin side-chains being linked), wherein:
the base solution comprises proteins selected from the group consisting of: mucin (paragraph [0188] “a degree of polymerization” and in-depth discussion at paragraph [0006] for mucin side-chains being linked), and
water (paragraph [0086]).
Marzorati does not disclose:
A three-dimensional gradient substrate for microbial culture comprising a gel with a cross-linking gradient
obtained by: contacting a base solution and a cross-linking medium via a semipermeable membrane, wherein the base solution is located above the semipermeable membrane and the cross-linking medium is located below the semipermeable membrane; incubating the base solution with the cross-linking medium between 2 min and 20 h at a temperature between 4 °C to 25 °C to allow diffusion of salts and a culture medium thereby forming the gel with the cross-linking gradient; and removing the gel
wherein the base solution comprises a polysaccharide selected from the group consisting of: sodium alginate and pectin
the base solution comprises … a protein selected from the group consisting of: serum albumin
the base solution comprises … sodium chloride
the cross-linking medium comprises a salt selected from the group consisting of: calcium chloride and calcium gluconate
the culture medium selected from the group consisting of: Mueller Hinton and Luria Bertani, and distilled water,
wherein the culture medium and the salts range from the higher concentration at a bottom side of the three-dimensional gradient substrate to the lower concentration at the surface of the three-dimensional gradient substrate,
wherein the oxygen tension ranges in a deepest region of the gel reaches oxygen tension from 150 μmol/L to 210 μmol/L in a deepest region of the gel,
and wherein the three-dimensional gradient substrate comprises the storage modulus G’ between 2 Pa and 3,000 Pa for shear strain frequencies from 0.1 Hz to 20 Hz
and wherein the three-dimensional gradient substrate has a thickness greater than 2 mm and equal to or less than 3 mm.
Regarding feature 1, specifically the phrase “gradient”, Allbritton discloses the limitation, see previous Office Action.
Regarding feature 2, the limitation is a product-by-process limitation. “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” MPEP § 2113.
Regarding feature 3, Lourenço or Allbritton disclose the limitation, see previous Office Action.
Regarding feature 3, specifically the limitation “and pectin”, the limitation is claimed in the alternative. No further rejections are required at this time.
Regarding feature 4, the limitation “serum albumin” is claimed in the alternative. No further rejections are required at this time.
Regarding feature 5, Lourenço discloses the limitation, see previous Office Action.
Regarding feature 6, Deutsch discloses the limitation, see previous Office Action.
Regarding feature 7, MacWilliams discloses the limitation, see previous Office Action.
Regarding feature 8, Allbritton discloses the limitation, see previous Office Action.
Regarding the features 9-11, the prior art of record, alone or in combination, does not teach or fairly suggest these features within the claim environment.
Regarding the dependent claim 17, this claim contains allowable subject matter for the same reason as the base claim upon which it depends.
Response to Arguments
Applicant’s arguments filed 04/14/2026 have been fully considered but they are not persuasive.
Regarding the Applicant arguments, pgs. 4-7 of 8, the rejection to the claims under 112(a) is sustained due to the unclear demarcation of endpoints in the graphs being used to support the claim limitations. The claimed ranges are not clearly supported in the graphical domain or range endpoints. For example, from the Applicant arguments, pg. 5 of 8, the lower boundary of the range is claimed to be 40 Pa, but the line drawn to the vertical axis may or may not be at 40 Pa.
Regarding the allowable subject matter, the claim limitations currently recited disclose the conditions for oxygen tension and storage modulus G’ under the range of a thickness from 2 mm (exclusive) to 3 mm (inclusive) of the three-dimensional gradient substrate thickness. No prior art could be found to teach an obvious combination of these limitations: 2-3 mm thick layer substrates of those claimed with internal gradients in oxygen, nutrients, and viscoelasticity. The current amendments regarding the three-dimensional gradient substrate properties overcome the 35 U.S.C. § 103 rejections.
Conclusion
THIS ACTION IS MADE FINAL. 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.
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/N.G.E./Examiner, Art Unit 1799
/MICHAEL A MARCHESCHI/Supervisory Patent Examiner, Art Unit 1799
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