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 Status
To expedite the compact prosecution, the Examiner is pursuing the amended claims dated 03 July 2024, in which applicant canceled claims 1-39; and added claims 40-62. Therefore, claims 40-62 are pending in the application.
Priority
This application was filed 07/03/2024 and is a 371 application of PCT/US2023/010096 filed on 01/04/2023, which claims benefit to the Provisional Application 63296276 filed on 01/04/2022.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994)
The disclosure of the prior-filed application, Application No. 63296276, filed 01/04/2022 fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
The prior filed provisional application 63296276 does not disclose the limitations of claim 40 regarding (ii) seeding the first IPHB with a first cell type of interest; (iii) seeding the second IPHB with a second cell type of interest, wherein the first cell type of interest is different than the second cell type of interest; (iv) feeding the first cell type of interest with a first culture media, and allowing the first cell type of interest to propagate throughout a first network of microporous channels and/or chambers towards the second IPHB; (v) feeding the second cell type of interest with a second culture media, and allowing the second cell type of interest to propagate throughout a second network of microporous channels and/or chambers towards the first IPHB; and (vi) forming a first interface between the first cell type and the second cell type. Therefore claims 40-62 are not found to have support in the 63296276 provisional application and have been examined with the effective filing date of the PCT/US2023/010096 parent application which is 01/04/2023.
Thus, the earliest possible priority for the instant application is 01/04/2023.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/03/2024, 10/10/2025, 01/23/2026, and 07/30/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner and the signed and initialed PTO Forms 1449 are mailed with this action.
Objection to Drawings
The drawings are objected to under 37 CFR 1.84(h)(5) because it appears to be a typographical error on p. 4 lns 18 and 24 of the description wherein the brief descriptions of Figure 32A and Figure 32 B do not seem to correspond to Figure 32A and Figure 32B as presented in the Drawings. Another typographical error on page 6, lns 12 and 16 of the description wherein reference is erroneously made to Figure 23A and Figure 23B, respectively. Therefore, the specification is a show(s) modified forms of construction in the same view. 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.
Title Objection
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. See MPEP 606.01
The following title is suggested:
“3D Multicellular Culture System Comprising Interlocking Porous Hydrogel Blocks.”
Claim Objections
Claims 43, 44-46, 50, 52 and 54 are objected to because of the following informalities:
Claim 40 is recited “a respective continuous polymeric matrix material,” however dependent claims 43, 44, 45, 50, 52 and 54 are recited inconsistent terminology as “continuous polymeric matrix material” (see the requirement of 37 CFR 1.71(a) for "full, clear, concise, and exact terms"). Therefore, appropriate correction is required.
Claim 46 is "gently and degraded" creates ambiguity in the claim. It would appear that this arises from a typographical error wherein the aforementioned phrase was employed instead of the phrase "gently degraded." Appropriate correction is required.
Specification Objection
This specification is objected to because it recited the term "Mitotracker" (p 5, ln 29); "PrestoBlue" (p. 7, ln 14); "PicoGreen" (p. 7, ln 16); "Accutase" (p. 13, ln 24); "Dermalife" (p 40, ln 27); "AlexaFluor" (p. 42, ln 13); "Revolve" (p. 42, ln 15); "UPlanSApo" (p. 42, ln 18); "lmageXpress" (p. 43, ln 26), and "Prism" (p. 43, ln 37) without appropriate or a proper trademark symbol. These are a trade name or a mark used in commerce, and 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 (see MPEP 608.01(v)). Therefore, appropriate correction is required.
Claim Rejections - 35 USC § 112
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 40-48, and 57 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.
The phrase "A method of growing of tissue ex vivo cells" is described in claim 40. It can be understood that the use of interlocking porous hydrogel blocks (IPHB) (i.e., ex vivo) to proliferate (grow) cells (target cell type) is described in claim 1. However, there is no description regarding "tissue" in claim 40, therefore, the phrase "growing tissue ex vivo cells" creates ambiguity in the claim as its meaning is unclear. It is not clear how "tissue" is related to the invention of claim 40, which renders the claim indefinite. Appropriate correction is required.
Claim 41 is indefinite for failing to particularly point out and distinctly claim the subject matter. The inclusion of the phrase "the second network of microporous channels and/or chambers, wherein the first structure is different than the second structure" creates ambiguity in the claim. it is not clear what is the meant by wherein the first structure and the second structure because the claim does not clearly identify the element to which these term refer? The rejection may be obviated by amending the claim 41 to recite "the second network of microporous channels and/or chambers has a second structure, wherein the first structure is different than the second structure".
The phrase “such as … derived from petroleum” is recited in claim 44, however, it is not clear whether the recited synthetic polymers are required to derived from petroleum or whether the phrase “such as” merely introduces an exemplary embodiment. MPEP 2173.05(b) states Datamize LLC v. Plumtree Software, Inc., 417 F.3d 1342, 1350, 75 USPQ2d 1801, 1807 (Fed. Cir. 2005)); see also Interval Licensing LLC v. AOL, Inc., 766 F.3d 1364, 1373, 112 USPQ2d 1188 (Fed. Cir. 2014) (holding the claim phrase "unobtrusive manner" indefinite because the specification did not "provide a reasonably clear and exclusive definition, leaving the facially subjective claim language without an objective boundary"). Accordingly, claim scope cannot depend solely on the unrestrained, subjective opinion of a particular individual purported to be practicing the invention. The scope of the claim cannot be determined with reasonable certainty. Therefore, the term “such as” in claims 42, 44-47, 57 is a subjective term which renders the claim indefinite, because it is unclear whether the subsequently recited subject matter constitutes a required claim limitation or merely and example. The specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Therefore, clarification or appropriate amendment is required to particularly point out and distinctly claim the invention.
Claim 42 recites “at least about” The metes and bounds of the term “at least about" are unclear because there are two limitations in this phrase: "at least" and "about". The limitation "about" is broad, but not indefinite. Similarly, the limitation "at least" is broad, but not indefinite. However, "at least about" is indefinite because the metes and bounds of limitation "at least about" cannot be determined. “About” indicates values below, which necessarily fails to meet the "at least" requirement. Appropriate correction is required.
Dependent claim 43 is recited “the second continuous polymeric matrix material,” however, the independent claim 40 does not introduce this limitation, therefore there is insufficient antecedent basis for this limitation. Appropriate correction is required.
Claims 43, 45, and 47 are indefinite is indefinite for failing to particularly point out and distinctly claim the subject matter. The elements "non-degradable hydrogel material" (claim 43, line 3) and "selectably degradable hydrogel material" (claims 45 and 47), are defined with indefinite articles, causing a lack of clarity as to whether they are intended to refer to the same elements previously defined in the claims or an additional element thereto.
Claim 46 recited a feature in parentheses, such as "e.g., DNA, RNA", raises uncertainty as to whether this feature is optional or always present. The term “e.g.” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Claim 46, further recited a relative and subjective terms, such as "can be gently degraded” and “weak acid", creates a lack of clarity. Claim scope cannot depend solely on the unrestrained, subjective opinion of a particular individual purported to be practicing the invention. Appropriate correction is required.
Claim 48 is indefinite for failing to particularly point out and distinctly claim the subject matter. The inclusion of the phrase "different that the first cell type" creates ambiguity in the claim. It would appear that this arises from a typographical error wherein the aforementioned phrase was employed instead of the phrase" different than the first cell type."
Claim 48 also recited “forming a second interface between the first cell type and the second cell type” however, the scope is not fully supported by the description and does not comply with MPEP 2173.03 (see Correspondence between the specification and claims is required by 37 CFR 1.75(d)(1)). The claimed feature wherein the second interface is formed between the first cell type and the second cell type is not described in the description. Instant SPEC disclosed on page 29, lns 8-10 that the second interface is formed between the second cell type and the third cell type. Appropriate correction is required.
Claim 57 is indefinite for failing to particularly point out and distinctly claim the subject matter. The inclusion of the phrase "(iv) any combination of claims (i), (ii) and (iii)" creates ambiguity in the claim as its meaning is unclear. It would appear that this combination is referring to the combination of features (i), (ii) and (iii), not to claims 1, 2 or 3. Appropriate correction is required.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
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 40-47, 49-53, 56, and 58 are rejected under 35 U.S.C. 103 as being unpatentable over Hickey et al., (WO2020227835A1; cited in IDS files 07/03/2024; hereinafter “Hickey”), in view of Zhang et al., (ACS Appl. Mater. Interfaces 2019, 11, 25427−25435; cited in IDS files 07/03/2024; hereinafter “Zhang”).
Regarding claim 40, Hickey discloses a method of growing of tissue ex vivo cells (p. 6, 8th ¶) comprising:
interlocking together a plurality of interlocking porous hydrogel blocks (IPHB) including a first IPHB and a second IPHB, wherein each of the plurality of IPHBs include a respective three-dimensional (3D) macrostructure defined by a respective continuous polymeric matrix material and a respective network of microporous channels and/or chambers extending throughout the respective continuous polymeric matrix material (p 2, 3rd ¶; p. 5, 7th ¶; p. 7, 5th ¶) and wherein the respective 3D macrostructure structures each include at least one respective interlocking male component and at least one respective interlocking-female component (p. 24 6th ¶; p. 25, 1st ¶);
seeding the first IPHB with a first cell type of interest (p 25, 4th ¶);
seeding the second IPHB with a second cell type of interest, wherein the first cell type of interest is different than the second cell type of interest (p 3, 1st ¶; p. 61, 3rd ¶);
allowing the first cell type of interest to propagate throughout a first network of microporous channels and/or chambers towards the second IPHB;
allowing the second cell type of interest to propagate throughout a second network of microporous channels and/or chambers towards the first IPHB and;
the composite scaffold biomaterial may comprise an interface between adjacent scaffold biomaterial subunits which may mimic a tissue interface, such as a bone-fibroblast tissue interface therefore, interlocking is forming a first interface between the first cell type and the second cell type (p 3, 4th ¶, 10th ¶ and 1st ¶)
Yet Hickey does not specifically teach feeding the first cell type of interest with a first culture media, and feeding the second cell type of interest with a second culture media, and the respective 3D macrostructures each comprise a respective top surface, a respective bottom surface, and a respective thickness defined by at least one respective side edge extending from the respective top surface to the respective bottom surface. However, such was known in the prior art.
Zhang teaches hydrogels with top and bottom surfaces with a certain thickness (p 25430, col 2, 2nd ¶; p. 25431, col 1, 1st ¶; Fig. 2 and Fig. 4a, 4b), wherein the hydrogel surface has >95 wt % water content, the P(AAm−AMPS)/alginate DN hydrogel and exhibits significant compressive strength and stress reaching values as high as 60 kPa (Figure S7). The hydrophilic nature and the high cell viability of the AMPS polymer and the specific surface structure with a gradient in cross-linking density, the as prepared P(AAm−AMPS)/alginate DN hydrogel has potential as a load-bearing soft material for tribological applications (see p. 25432 right col. 4th ¶ of Zhang).
According, since Spiderwort teaches interlocking porous hydrogels with three-dimensional (3D) macrostructure defined by a respective continuous polymeric matrix material and a respective network of microporous channels and/or chambers and seeding the IPHBs with two different cell types, and Zhang teaches hydrogels with top and bottom surfaces with a certain thickness, it would have been obvious to one of ordinary skill in the art to combine teachings of Hickey and Zhang to develop interlocking porous hydrogel blocks of 3D structure with top, bottom surfaces and a certain thickness and with a network of microporous channels for growing efficiently tissue ex vivo cells, and to use routine experimentation to optimize medium for optimal cell growth wherein each cell type may have a specific medium of growth use routine experimentation to optimize medium for optimal cell growth wherein each cell type may have a specific medium of growth (p. 25432 right col. 4th ¶ of Zhang).
Regarding claim 41, Hickey teaches that the composite scaffold biomaterial may comprise at least two scaffold biomaterial subunits which are structurally different from one another (p. 28 3rd ¶).
Regarding claim 42, Hickey teaches that the scaffold biomaterials as described herein may comprise decellularized plant or fungal tissue comprising a pore size of about 100 to about 200 μm(p. 23 6th ¶). Further, Hickey discloses that the xylem channels (38.50μm± 6.86) and phloem channels (21.52 μm ± 5.0) lie within the 10-100μm diameter suitable for optimal myoblast alignment (p. 78 1st ¶).
Regarding claims 43-47, Hickey teaches that the scaffold biomaterial subunits (e.g., IPHB) may comprises a non-degradable (i.e., synthetic polymer) hydrogel (i.e., PEG, PVA) and/or degradable hydrogel material (i.e., alginate, fibrin, fibronectin, agar).
Regarding claims 49-50, and 58, Hickey teaches that the composite scaffold biomaterial may comprise an interface between adjacent scaffold biomaterial subunits which may mimic a tissue interface, such as a bone-fibroblast tissue interface. The first cell type, the second cell type, or both, may be animal cells, such as mammalian cells or human cells. In certain embodiments, the scaffold biomaterials may comprise ECM deposition at least one interface between adjacent scaffold biomaterial subunits (p. 25 4th ¶), therefore, culturing the cells on the decellularized scaffold biomaterial, thereby aligning the cells along the one or more channels or grooves (p. 31 6th ¶).
Regarding claims 51 and 53, Hickey teaches that the methos further comprises freezing the first IPHB before or after forming artificial tissue samples (p. 23 1st ¶).
Regarding claim 52, Hickey teaches that the two or more scaffold biomaterial subunits may be assembled into the composite scaffold biomaterial and held together via complementary interlocking geometry of the two or more scaffold biomaterial subunits (p. 24 6th ¶). The composite scaffold biomaterial may comprise an interface between adjacent scaffold biomaterial subunits which may mimic a tissue interface, such as a bone-fibroblast tissue interface (p. 25 4th ¶).
Regarding claim 56, Hickey teaches that depending on the solvent and/or intended use of the products, neutralization and/or washing may be performed to remove residual solvent and other reagents so as to prevent undesirable contamination (p. 38 1st ¶).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 40, 48-49, and 56 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 23, 25, 27, 30-32, 34-35, and 37 of copending application no. 18/726671 (US20250084379A1). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The subject matter claimed in the instant application is disclosed in the reference claims as follows:
Copending claims 23, 25, 27 and 32, 34, 35, would anticipate the instant claim 40 directed to interlocking together a plurality of interlocking porous hydrogel blocks thereto, if it were available as prior art. Since it is not, the claims are patentably indistinct.
Copending claims 30, 31 would anticipate the instant claims 49 and 56 directed to a step of harvesting at least a portion of first cells from the first cell type of interest located throughout the first network of microporous channels, if it were available as prior art. Since it is not, the claims are patentably indistinct.
Copending claim 37 would anticipate the instant claim 48 directed to interlocking a third IPHB directly to the second IPHB, and seeding the third IPHB with a third cell type of interest, if it were available as prior art. Since it is not, the claims are patentably indistinct.
Since the instant application claims are anticipated by cited application claims, said claims are not patentably distinct.
Subject Matter Free of Art
Although Hickey teaches two or more scaffold biomaterial subunits may be assembled into the composite scaffold biomaterial and held together via complementary interlocking geometry of the two or more scaffold biomaterial subunits (p. 24 6th ¶). Yet Hickey does not specifically teach seeding the third IPHB with a third cell type of interest or fourth cell type. Claims 48, 54, 55, 57, 59-62 are encompassing the specifically third cells from the third cell type of interest located throughout network of microporous channels and fourth cells from the fourth cell type of interest located throughout network of microporous channels. Since claims 48, 54, 55, 57, 59-62 depend from rejected base independent claim 40. The scope of Claim 40 would be free of the art, if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Pertinent References
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure is the following:
[AltContent: textbox ([img-media_image1.png])]Screen captures from YouTube video clip entitled " Types of 3D Cell Culture - Scaffold 3D Cell Culture," uploaded on Mar 28, 2022 by user " clevaforce". Retrieved from Internet: < https://youtu.be/RcrdHo_m8ew?si=iiZzxHeBnB0XrUxd >.
Hereinafter Clevaforce et al. provide a method of 3D cell culture approach where hydrogel scaffolds are aid out to replicate the structure of the tissue of interest.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MASUDUR RAHMAN whose telephone number is 571-272-0196. The examiner can normally be reached M-F 8-5 (EST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached on (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MASUDUR RAHMAN/ Patent Examiner, Art Unit 1633
/JEREMY C FLINDERS/ Primary Examiner, Art Unit 1684
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