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 .
Claims 1-5, 7-8, 11-12, 14-18, and 25-32, of record 1/31/2026, are pending and subject to prosecution.
The amendment to the claims filed on 1/31/2026, does not comply with the requirements of 37 CFR 1.121(c) because a character in line 3 of claim 8 is both bracketed and underlined. Amendments to the claims filed on or after July 30, 2003 must comply with 37 CFR 1.121(c) which states (emphasis added):
(c) Claims. Amendments to a claim must be made by rewriting the entire claim with all changes (e.g., additions and deletions) as indicated in this subsection, except when the claim is being canceled. Each amendment document that includes a change to an existing claim, cancellation of an existing claim or addition of a new claim, must include a complete listing of all claims ever presented, including the text of all pending and withdrawn claims, in the application. The claim listing, including the text of the claims, in the amendment document will serve to replace all prior versions of the claims, in the application. In the claim listing, the status of every claim must be indicated after its claim number by using one of the following identifiers in a parenthetical expression: (Original), (Currently amended), (Canceled), (Withdrawn), (Previously presented), (New), and (Not entered).
(1) Claim listing. All of the claims presented in a claim listing shall be presented in ascending numerical order. Consecutive claims having the same status of “canceled” or “not entered” may be aggregated into one statement (e.g., Claims 1–5 (canceled)). The claim listing shall commence on a separate sheet of the amendment document and the sheet(s) that contain the text of any part of the claims shall not contain any other part of the amendment.
(2) When claim text with markings is required. All claims being currently amended in an amendment paper shall be presented in the claim listing, indicate a status of “currently amended,” and be submitted with markings to indicate the changes that have been made relative to the immediate prior version of the claims. The text of any added subject matter must be shown by underlining the added text. The text of any deleted matter must be shown by strike-through except that double brackets placed before and after the deleted characters may be used to show deletion of five or fewer consecutive characters. The text of any deleted subject matter must be shown by being placed within double brackets if strike-through cannot be easily perceived. Only claims having the status of “currently amended,” or “withdrawn” if also being amended, shall include markings. If a withdrawn claim is currently amended, its status in the claim listing may be identified as “withdrawn—currently amended.”
(3) When claim text in clean version is required. The text of all pending claims not being currently amended shall be presented in the claim listing in clean version, i.e., without any markings in the presentation of text. The presentation of a clean version of any claim having the status of “original,” “withdrawn” or “previously presented” will constitute an assertion that it has not been changed relative to the immediate prior version, except to omit markings that may have been present in the immediate prior version of the claims of the status of “withdrawn” or “previously presented.” Any claim added by amendment must be indicated with the status of “new” and presented in clean version, i.e., without any underlining.
(4) When claim text shall not be presented; canceling a claim.
(i) No claim text shall be presented for any claim in the claim listing with the status of “canceled” or “not entered.”
(ii) Cancellation of a claim shall be effected by an instruction to cancel a particular claim number. Identifying the status of a claim in the claim listing as “canceled” will constitute an instruction to cancel the claim.
(5) Reinstatement of previously canceled claim. A claim which was previously canceled may be reinstated only by adding the claim as a “new” claim with a new claim number.
As noted above, the amendment under consideration herein fails to comply with 37 CFR 1.121 because the claim listing contains text that is both bracketed and underlined. The amendment could be therefore considered non-responsive. In the interest of compact prosecution, the amendment at issue will not be considered non-responsive, however, any future responses failing to comply with 37 CFR 1.121 will be held non-responsive and will not be considered.
Status of Prior Rejections/Response to Arguments
RE: Objection to the specification:
The amendment to the specification is effective to obviate the objection. The objection is withdrawn.
RE: Objection to claims 7-8, 11, and 21:
The cancellation of claim 21 renders the objection thereto moot.
The amendment to claims 7-8 and 11 is effective to obviate the objection. The objection is withdrawn.
RE: Rejection of claims 1-2, 6-7, 13-14, and 16-18 under 35 U.S.C. 102(a)(1) and 102(a)(2) over Murphy et al. (US 20200017823 A1):
RE: Rejection of claims 1-3, 6-7, 13-14, and 16-18 under 35 U.S.C. 103 over Murphy et al. (US 20200017823 A1):
RE: Rejection of claims 1-9 and 13-18 under 35 U.S.C. 103 Murphy et al. (US 20200017823 A1) in view of Xiao et al. (Polymer, 2022):
RE: Rejection of claims 1-3, 6-7, 10-14, and 16-24 under 35 U.S.C. 103 over Murphy et al. (US 20200017823 A1) in view of Grigoryan et al. (Science, 2019):
The cancellation of claims 6, 9-10, 13, and 19-24 renders the rejections thereto moot.
The amendment to claims 1 is effective to obviate the rejections. The rejections are withdrawn.
New Objections/Rejections
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.821 - 1.825 because it does not contain a "Sequence Listing" as a separate part of the disclosure or a CRF of the “Sequence Listing”. Nucleotide and/or amino acid sequences appearing in the claims and specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.821(c)-(d).
Required response - Applicant must provide:
A "Sequence Listing" part of the disclosure; together with
An amendment specifically directing its entry into the application in accordance with 37 CFR 1.825(a)(2);
A statement that the "Sequence Listing" includes no new matter as required by 37 CFR 1.821(a)(4); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(a)(3).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
If the "Sequence Listing" part of the disclosure is submitted according to item 1) c) or d) above, applicant must also provide:
A CRF in accordance with 37 CFR 1.821(e)(1) or 1.821(e)(2) as required by 1.825(a)(5); and
A statement according to item 2) a) or b) above.
Claim Interpretation
Claim 1 recites a three-dimensional biocompatible hydrogel comprising a hydrogel matrix formed by photopolymerizing a photoink comprising a norbornene-functionalized polymer, a crosslinker, a photoinitiator, and a first peptide; a plurality of internal channels within the hydrogel matrix; and at least one additional peptide, different from the first peptide, covalently bound to a channel-lining region of at least one of the plurality of internal channels; wherein the first peptide is covalently bound within a bulk region of the hydrogel matrix during said photopolymerizing; and wherein the at least one additional peptide is covalently bound to the channel-lining region by irradiating the hydrogel matrix after perfusing the at least one additional peptide through the plurality of internal channels. The hydrogel is defined using product-by-process language. Product-by-process limitations are considered only in so far as the method of production imparts distinct structural or chemical characteristics or properties to the product. Therefore, if the product as claimed is the same or obvious over a product of the prior art (i.e., is not structurally or chemically distinct), the claim is considered unpatentable over the prior art, even though the prior art product is made by a different process. See MPEP 2113. In the instant application, because the processes described in claim 1 do not distinguish the hydrogel structurally from a hydrogel comprising the same components generated by other methods, the hydrogel is interpreted as comprising any hydrogel comprising a norbornene-functionalized polymer, crosslinker, photoinitiator, and first peptide bound within a bulk region and comprising a plurality of internal channels wherein at least one additional peptide is covalently bound.
Claim Rejections - 35 USC § 112
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.
Claim 15 is 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 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.
Claim 15 was amended to require a crosslinker having a molecular weight of 5000 Daltons in an amount of about 3 to about 15 mM. The original disclosure does not provide support for a crosslinker with a 5 kDa molecular weight. The specification generically discloses PEG dithiol and dithiothreitol as crosslinkers and that the crosslinker can be present in a concentration of about 3 mM to about 15 mM (See ¶0013, 0017, 0037, 0039-0040, 0043-0044, 0056, and 0071). However, no mention is made of a crosslinker that meets the requirements of the claimed limitation, which renders the amended limitation new matter.
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 27-32 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 27 recites the limitation “the plurality of interpenetrating channels” in line 3-4. There is insufficient antecedent basis for this limitation in the claim. Dependent claims 28-32 are included in the rejection.
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.
Claims 1-4, 7-8, 11, 14, 17, and 26-30 are rejected under 35 U.S.C. 103 as being unpatentable over Miller et al. (US 20220333050 A1), evidenced by Sigma-Aldrich (Product data sheets, 2026), in view of Lutolf et al. (US 20030166833 A1).
Regarding claims 1-2, 7, 11, 14, 17, and 26-30: Miller et al. teach methods for coating the surface of a target material with cells (See Abstract). The surface may be luminal, such as that of 3D printed hollow channels (which read on “internal channels”) (See Abstract and ¶0006, 0017, and 0019). The hydrogel matrix can include first and second or more tubular channels (which read on “a plurality”) that are interpenetrating channels (See ¶0031, 0042, and 0044). The tubular channels can be perfusable and can be lined with endothelial cells (See ¶0042). The target material can be a hydrogel formed by stereolithography or casting around a sacrificial template and can be photopolymerized (See ¶0020, 0024, and 0026). Materials suitable for the hydrogel include PEG-norbornene or norbornene-functionalized gelatin (which read on “a norbornene-functionalized polymer”) (See ¶0063). The hydrogel can comprise biocompatible light-absorbing material such as tartrazine and curcumin (See ¶0028). Photoinitiators can include LAP (which reads on “lithium phenyl-2,4,6-trimethylbenzoylphosphinate”) (See ¶0026). Crosslinking agents can include PEG-dithiol and dithiothreitol (See ¶0063). The hydrogel matrix may be constructed using a digital light processing system to project a light source for polymerization (See ¶0046). The hydrogel matrix can include cells embedded within (See ¶0031).
Cells can be seeded on the channel lumens by local polymerization of a carrier composition (See Abstract). The carrier composition can comprise a photoinitiator such as Irgacure 2959 (which reads on “a Norrish type-I photoinitiator” and “2-hydroxy-1-[4-(2-hydroxyethoxy) phenyl]-2-methyl-1-propanone”) (See ¶0056 and 0065). The carrier composition can further include biological materials such as biological micromolecules or macromolecules or active agents such as peptides (which reads on “at least one additional peptide”) (See ¶0072, 0078, and 0081-0082).
Miller et al. do not expressly teach the inclusion of a first peptide, which is not a crosslinking peptide, in a bulk region of the hydrogel.
Lutolf et al. teach the incorporation of proteins into matrices such as hydrogels (See ¶0019 and 0061-0062). RGD peptides can be incorporated into the matrix to optimize cell ingrowth and migration (See ¶0071). Lutolf et al. teach an embodiment wherein a gel comprised a peptide comprising the sequence GCGYGRGDSPG (which reads on “consist of 3 to 30 amino acids and… contain a cysteine residue”) attached to a multi-armed PEG polymer (See ¶0142 and 0144).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Miller et al. to comprise addition of an adhesion peptide, such as the RGD peptide taught by Lutolf et al. One would have been motivated to make this modification because Lutolf et al. teach that such a peptide can increase cell growth within a bulk hydrogel (See ¶0071). There would be a reasonable expectation of success in doing so because an RGD peptide could be readily incorporated into the hydrogel of Miller et al.
Regarding claim 3: Following the discussion of claims 1-2, 7, 11, 14, 17, and 26-30, Miller et al. do not expressly teach the molarity of PEG-norbornene. However, 4-arm or 8-arm PEG-norbornene or norbornene-functionalized gelatin can be present at concentrations of about 1-20% wt (See ¶0063). Using the formula wherein molarity equals (% wt × density per 100 g × 10)/(molar mass) and assuming an average molar mass of 10 kDa for 4-arm PEG-norbornene (See Sigma-Aldrich product data sheet), use of 1-20% PEG-norbornene corresponds to a range of 1-20 mM (which reads on “about 1 to about 10 mM”). Where the claimed ranges overlap or lie inside ranges disclosed by the prior art, a prima facie case of obviousness exists. See MPEP 2144.05(I).
Regarding claim 4: Following the discussion of claims 1-2, 7, 11, 14, 17, and 26-30, Miller et al. do not expressly teach the use of hyaluronic acid-functionalized norbornene. However, Miller et al. teach that other materials that can be used in the photopolymerizable hydrogel include -ene-modified hyaluronic acid (See ¶0026). One of ordinary skill in the art would therefore have found it obvious to substitute hyaluronic acid for PEG or gelatin in norbornene-functionalized polymers. Substitution of one known element for another known element is considered to be prima facie obvious, absent a showing that the substitution yields more than expected results. See MPEP 2143(I)(B).
Regarding claim 8: Following the discussion of claims 1-3, 7, 11, 14, 17, and 26-30, Miller et al. do not expressly teach the molarity of LAP. However, photoinitiators such as LAP can be used at concentrations of about 0.01-1% wt (See ¶0065). Using the formula wherein molarity equals (% wt × density per 100 g × 10)/(molar mass) and assuming a molar mass of 294 g (See Sigma-Aldrich product data sheet), use of 0.01-1% LAP corresponds to a range of 0.03-34 mM (which reads on “about 10 to about 300 mM”). Where the claimed ranges overlap or lie inside ranges disclosed by the prior art, a prima facie case of obviousness exists. See MPEP 2144.05(I).
Claims 1-4, 7-8, 11-12, 14, 17, and 26-30 are rejected under 35 U.S.C. 103 as being unpatentable over Miller et al. (US 20220333050 A1), evidenced by Sigma-Aldrich (Product data sheets, 2026), in view of Lutolf et al. (US 20030166833 A1), further in view of Grigoryan et al. (Science, 2019), of record.
The teachings of Miller et al., Sigma-Aldrich, and Lutolf et al. are set forth in the rejection above and are incorporated herein in their entirety.
Regarding claim 12: Following the discussion of claims 1-4, 7-8, 11, 14, 17, and 26-30, Miller et al., evidenced by Sigma-Aldrich, modified by Lutolf et al., render obvious a hydrogel comprising photoabsorbers but do not expressly teach photoabsorber concentrations.
Grigoryan et al. teach the addition of tartrazine, curcumin, and anthocyanin for absorbing light in printed hydrogels (See page 458, col. 3, full ¶1; page S3, ¶4; and fig. S4). Tartrazine was used at concentrations of 1, 2.255, 3.5, and 5 mM, and curcumin and anthocyanin were used at concentrations of 1, 2, and 3 mM (which read on “about 1 to about 5 mM”) (See fig. S4).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify method of making a hydrogel rendered obvious by Miller et al., Sigma-Aldrich, and Lutolf et al. to comprise tartrazine or curcumin concentrations such as are taught by Grigoryan et al. One would have been motivated to make this modification because the use of such concentrations by Grigoryan et al. suggest that they are appropriate for use in hydrogels (See fig. S4), and one of ordinary skill would have a reasonable expectation of success in doing so because photoabsorber concentration could be readily adjusted.
Claims 1-4, 7-8, 11, 14, 16-18, and 26-30 are rejected under 35 U.S.C. 103 as being unpatentable over Miller et al. (US 20220333050 A1), evidenced by Sigma-Aldrich (Product data sheets, 2026), in view of Lutolf et al. (US 20030166833 A1), further in view of Lippmann et al. (US 20240050627 A1).
The teachings of Miller et al., Sigma-Aldrich, and Lutolf et al. are set forth in the rejection above and are incorporated herein in their entirety.
Regarding claims 16 and 18: Following the discussion of claims 1-4, 7-8, 11, 14, 17, and 26-30, Miller et al., evidenced by Sigma-Aldrich, modified by Lutolf et al., render obvious a hydrogel comprising internal channels lined with covalently-attached endothelial cells and a peptide but do not teach a specific peptide.
Lippmann et al. teach materials for promoting large blood vessel growth, including a crosslinked hydrogel having a chemically attached cadherin-derived peptide (See Abstract). The peptide can comprise a HAV motif, such as HAVDIGGGCE (which reads on “consist of 3 to 30 amino acids and… contain a cysteine residue”) (See ¶0063 and 0068-0069).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Miller et al., evidenced by Sigma-Aldrich, modified by Lutolf et al. to comprise luminal tethering of the peptide taught by Lippmann et al. One would have been motivated to make this modification because Lippmann et al. teach that such a peptide can be found in a hydrogel that promotes blood vessel growth (See ¶0006, 0039, 0056-0057, and 0066-0069). There would be a reasonable expectation of success in making this modification because Lippmann et al. teach that the peptide can be chemically attached to hydrogels (See Abstract).
Claims 1-4, 7-8, 11, 14, 17, and 25-32 are rejected under 35 U.S.C. 103 as being unpatentable over Miller et al. (US 20220333050 A1), evidenced by Sigma-Aldrich (Product data sheets, 2026), in view of Lutolf et al. (US 20030166833 A1), further in view of Wong et al. (US 20140142370 A1).
The teachings of Miller et al., Sigma-Aldrich, and Lutolf et al. are set forth in the rejection above and are incorporated herein in their entirety.
Regarding claims 25 and 32: Following the discussion of claims 1-4, 7-8, 11, 14, 17, and 26-30, Miller et al., evidenced by Sigma-Aldrich, modified by Lutolf et al., render obvious a hydrogel comprising endothelial cell-lined channels but do not teach encapsulation of astrocytes within the hydrogel.
Wong et al. teach an artificial blood brain barrier comprising a vessel lined with endothelial cells embedded in a 3D extracellular matrix (See Abstract). The matrix can comprise a hydrogel having embedded cells including astrocytes (See ¶0015, 0027-0028, 0038, 0043, 0055, and 0057 and fig. 2).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Miller et al., evidenced by Sigma-Aldrich, modified by Lutolf et al., to comprise the incorporation of astrocytes into the bulk hydrogel. One would be motivated to make this modification because Wong et al. teach that an blood brain barrier model can be formed for developing therapies (See ¶0009). There would be a reasonable expectation of success in doing so because Miller et al. teach that cells can be embedded within the hydrogel matrix (See ¶0031).
Regarding claim 31: Following the discussion of claims 1-4, 7-8, 11, 14, 17, 25-30, and 32, Miller et al., modified by Lutolf et al., render obvious a hydrogel comprising endothelial cell-lined channels but do not teach the application of shear stress to the endothelial cell layer through fluid flow.
Wong et al. teach that an the artificial blood brain barrier allows for physiologically relevant variables such as shear stress and flow rate to be manipulated and studied (See ¶0030, 0046, 0050, 0060, and 0105).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Miller et al., evidenced by Sigma-Aldrich, modified by Lutolf et al., to further comprise application of fluid flow, as taught by Wong et al. One would be motivated to make this modification because Wong et al. teach that fluid flow can be used to recapitulate the shear stresses that brain microvessels typically encounter (See ¶0060 and 0105). There would be a reasonable expectation of success in doing so because Miller et al. teach that the channel networks can be perfusable (See ¶0017, 0042, and 0092).
Allowable Subject Matter
Claim 5 is objected to as being dependent upon a rejected base claim but would be allowable if rewritten in independent form including 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:
A survey of the prior art reveals that a concentration of 0.2-2 M norbornene-functionalized hyaluronic acid is exceedingly high (corresponding to approximately 6-60 kg in 1 L solution for a typical hyaluronic acid norbornene having an average molecular weight of 30 kDa), therefore, one of ordinary skill in the art would not find its use in a hydrogel obvious.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 JENNIFER S SPENCE, whose telephone number is 571-272-8590. The examiner can normally be reached M-F 8:30-5:30.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher M Babic, can be reached at 571-272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/J.S.S./Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633
Prosecution Insights