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 .
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This Action is in response to the papers filed on 10/10/2025.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 10/10/2025 has been entered.
Claims 40-43, 46, 74, 75, 77-80, and 83-87 are pending. Claims 40 and 84 are independent claims. Applicant amended claims 40 and 43, added claim 87, and cancelled claim 81 by amendment filed on 10/10/2025. Claims 84-86 are withdrawn from consideration pursuant to 37 CPR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claims.
Therefore, claims 40-43, 46, 74, 75, 77-80, 83 and 87 are currently under examination to which the following grounds of rejection are applicable.
Priority
The instant application is a CON of 16/466,735 filed 06/05/2019, now PAT 11577002. 16/466,735 is a 371 of PCT/US2017/064646 filed on 12/05/2017, which claims priority to
PRO 62/430,635 filed 12/06/2016. Thus, the earliest possible priority for the instant application is 12/06/2016.
Withdrawn Objections/Rejections in response to Applicants’ arguments or amendments
Claim Rejections - 35 USC § 103
In view of Applicants’ remarks filed 10/10/2025, the rejection of claims 40-43, 46, 74-75, 77, 79-80, 83 under 35 U.S.C. 103 as being unpatentable over Mao et al. (WO 2008/008229 A2, IDS) in view of Trkov et al. (Trkov S. et al. J Tissue Eng Regen Med. 2010, of record).35 U.S.C. 112(b) has been withdrawn.
A response to Applicant’s arguments with regard to a withdrawn rejection is moot. A response to any argument pertaining to a new or maintained rejection can be found below.
Maintained and modified rejections in response to Applicants’ arguments or amendments
Claim Interpretation in view of claim amendments
Claim 40 has been amended to recite “A system for producing a perfusable engineered vasculature, the system comprising: a) a cell-free three-dimensional hydrogel culture medium comprising a channel, wherein said channel comprises a mixture of endothelial cells (ECs) and mesenchymal stem cells (MSCs)”
The preamble of claim 40 recites “for producing”, which is intended use and will not be given patentable weight. Therefore, the claimed system is examined in relation to subparts of which the system is comprised (and to which the instant specification supports).
If the body of claim fully and intrinsically sets forth all limitations of the claimed invention, such as all the components of a composition, and the preamble merely states the intended use of the invention, rather than any distinct definition of the any of the claimed invention’s limitations, the preamble is not considered a limitation and is of no significance to claim construction. See MPEP § 2111.02
The phrase “a cell-free three-dimensional hydrogel culture medium comprising a channel wherein said channel comprises a mixture of endothelial cells (ECs) and mesenchymal stem cells (MSCs)” is not supported by the specifications (see relevant 112a rejection below).
Note that on Pg. 1 of Applicants’ remarks, the applicant states that [0136] of the published application states: Support for amended claim 40 is found in the application as originally filed, e.g., at least at page 3, lines 10-11 ("providing a mixture of ECs and MSCs into a hydrogel channel"); page 9, lines 16-20 ("fibrinogen and thrombin were then poured into the tissue chamber. After allowing for the formation of fibrin gel, the narrow gauge tube was removed to produce a channel within the fibrin gel…placing ECs, MSCs, or a combination of MSCs+ECs into the tissue channel"). However, these paragraphs nor the rest of the instant specification provide clarity to ascertain the metes and bounds of “a cell-free three-dimensional hydrogel culture medium comprising a channel wherein said channel comprises a mixture of endothelial cells (ECs) and mesenchymal stem cells (MSCs)”.
For the purpose of compact prosecution, the claim will be interpreted with respect to the system as requiring a hydrogel where cells are not present within the hydrogel, culture medium suitable for 3D culture, a channel and a mixture of endothelial cells wherein said channel comprises a mixture of endothelial cells (ECs) and mesenchymal stem cells (MSCs)”.
Claim Rejections - 35 USC § 112(b)
Claims 46, 79 and 83 are rejected under 35 USC § 112(b) 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.
Claims 46 and 83 which depend on claim 40 recite “ the tissue chamber” in line 1 . There is not proper antecedent bases for “ the tissue chamber” in the claims.
Claim 79 is indefinite is indefinite in the recitation of “at least approximately” for the following reason. “Approximately” encompasses values above and below a reference point whereas “at least” encompasses only values above the reference point. Therefore, the combination of both terms (at least approximately) is confusing because one term is including values above the reference point whereas the other term is excluding values above the reference point.
Double Patenting
Claims 40-43, 46, 74-75, 77-81 and 83 remain rejected and claim 87 is newly rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,577,002. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are obvious over the cited claims of U.S. Patent No. 11,577,002. Note: The rejection is modified for consideration of the amendments filed 10/10/2025.
Claim 1 of U.S. Patent No. 11,577,002 is directed to: A method for producing an engineered vasculature, the method comprising: providing a three-dimensional hydrogel culture medium comprising a channel; placing a mixture of endothelial cells (ECs) and mesenchymal stem cells (MSCs) in the channel at a concentration of approximately 10-100 million cells per cubic centimeter to form an organoid; and incubating the organoid to form an engineered vasculature.
Claim 40 of the instant application is directed to a system for producing a perfusable engineered vasculature, the system comprising: a) a cell-free three-dimensional hydrogel culture medium comprising a channel, wherein said channel comprises a mixture of endothelial cells (ECs) and mesenchymal stem cells (MSCs)”
Claim 79 of the instant application is directed to the system of claim 40, wherein the ECs and MSCs are present at a density of at least approximately 40 million cells per cubic centimeter. Claim 87 of the instant application is directed to the system of claim 40, wherein the mixture of ECs and MSCs comprises approximately 10-100 million cells per cubic centimeter.
Thus, the claims of the instant application are encompassed by, or overlap in scope significantly with, the claims of US Patent 11,577,002.
This rejection is necessitated by the decision of the Court of Appeals for the Federal Circuit in Pfizer Inc. v Teva pharmaceuticals USA Inc., 86 USPQ2d 1001, at page 1008 (March 2008), which indicates that there is no patentable distinction between claims to a product and a method of using that product disclosed in the specification of the application and that the preclusion of such a double patenting rejection under 35 USC 121 does not apply where the present application is other than a divisional application of the patent application containing such patentably indistinct claims.
The examiner notes that the instant invention is a CON of 16/466,735 (06/05/2019), now PAT 11577002. According to MPEP 804.01 states:
The 35 U.S.C. 121 prohibition applies only where the Office has made a requirement for restriction. The prohibition does not apply where the divisional application was voluntarily filed by the applicant and not in response to an Office requirement for restriction. The U.S. Court of Appeals for the Federal Circuit has concluded that the protection of 35 U.S.C. 121 does not extend to all types of continuing applications, stating that "the protection afforded by section 121 to applications (or patents issued therefrom) filed as a result of a restriction requirement is limited to divisional applications." Pfizer, Inc. v. Teva Pharmaceuticals USA, Inc., 518 F.3d 1353, 1362, 86 USPQ2d 1001, 1007-1008 (Fed. Cir. 2008).
Response to Applicants’ Arguments as they apply to the rejection of claims under Double Patenting
Applicants offer to provide a terminal disclaimer upon indication by the Examiner of allowable claims. However, Applicant’s request is not a proper response to the rejections of record as it neither traverses the grounds of rejection by providing specific arguments, nor indicates that a terminal disclaimer has been filed to overcome the rejection. As such, the rejections of record stand.
New objections/rejections necessitated by Applicants’ amendments
Claim Objections
Claim 40 is objected to because of the following informalities: In line 3, a step of “a)” is recited. However, only a single step is recited in this claim and notation of “a)” is unnecessary. Appropriate correction is required.
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.
Claims 40-43, 46, 74-75, 77, 79-80, 83 and 87 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.
MPEP § 2163.II.A.3.(b) states, “when filing an amendment an applicant should show support in the original disclosure for new or amended claims” and “[i]f the originally filed disclosure does not provide support for each claim limitation, or if an element which applicant describes as essential or critical is not claimed, a new or amended claim must be rejected under 35 U.S.C. 112, para. 1, as lacking adequate written description”. According to MPEP § 2163.I.B, “While there is no in haec verba requirement, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure” and “The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117”.Claim 40 has been amended to recite, “a system for producing a perfusable engineered vasculature, the system comprising: a) a cell-free three-dimensional hydrogel culture medium comprising a channel, wherein said channel comprises a mixture of endothelial cells (ECs) and mesenchymal stem cells (MSCs)”.
On page 1 of the remarks filed on 10/10/2025, Applicant on Pg. 1 of Applicants’ remarks, the applicant states that [0136] of the published application states: Support for amended claim 40 is found in the application as originally filed, e.g., at least at page 3, lines 10-11 ("providing a mixture of ECs and MSCs into a hydrogel channel"); page 9, lines 16-20 ("fibrinogen and thrombin were then poured into the tissue chamber. After allowing for the formation of fibrin gel, the narrow gauge tube was removed to produce a channel within the fibrin gel…placing ECs, MSCs, or a combination of MSCs+ECs into the tissue channel").
However, these paragraphs do not support “a cell-free three-dimensional hydrogel culture medium comprising a channel wherein said channel comprises a mixture of endothelial cells (ECs) and mesenchymal stem cells (MSCs)”.
At most, support is found for a system for producing a perfusable engineered vascular system comprising all of the following (see also described in the applicants’ remarks filed 10/10/2025, Pg. 6): A hydrogel comprising a hollow channel (tissue channel), wherein the hollow channel is formed entirely through the hydrogel, and made from polydimethylsiloxane. The hydrogel does not comprise cells within the hydrogel ITSELF. A mixture of endothelial cells (ECs) and mesenchymal stem cells (MSCs) are placed within the hollow channel of the hydrogel. Thus, the system comprises cells within the channel following this placement. The system is incubated in a bioreactor circulating media with a defined inlet port to supply fresh media and an outlet port to discard used media See application at page 3, lines 10-1 L page 9, lines 16-20; the examples at pages 31 and 32 and pages 32-33; and page 40, line 18 to page 41, line 14.
The closest prior art Mao et al. (WO 2008/008229 A2, IDS) and Trkov et al. (Trkov S. et al. J Tissue Eng Regen Med. 2010, of record) teach the use of hydrogels containing channels for cell culture systems.
Mao and Trkov do not teach a “a cell-free three-dimensional hydrogel culture medium comprising a channel wherein said channel comprises a mixture of endothelial cells (ECs) and mesenchymal stem cells (MSCs)” as recited in the instant claim.
Mao et al. teaches a tissue module (a system) comprising a biocompatible matrix (including a hydrogel) (Pg. 3, Paragraph 0015), vascular progenitor cells, and tissue progenitor cells (Pg., 71, Claim 1). Mao teaches the use of a biocompatible matrix (including a hydrogel) of the tissue module comprises at least one channel (Pg. 73, Claim 16). This module (including the cells) are combined together (mixed) (Pg. 71, Claim 2.) Mao teaches cultured tissue progenitor cells can be mesenchymal stem cells (Pg. 3, Paragraph 0013) and the vascular progenitor cells can be endothelial cells (Pg. 3, Paragraph 0014). Mao teaches media suitable for 3D hydrogel culture (Pg. 32, Paragraph 0128; Pg. 14 Paragraph 0054). Mao teaches seeding density of 0.0001 million cells (M) ml -1 up to about 1000M ml -1 in their system.
However, as pointed out by the applicant on Pg. 6 of the remarks filed 10/10/2025, Mao teaches this culture system in the context of cells grown within the hydrogels themselves and not inserted within the channel of the culture system as is taught by the instant application.
Additionally, the channels taught by Mao are not single channels formed for the direct purpose of cell implantation and the cells are fully excluded from within the channels themselves (Pg. 1, Figure A-D).
Trkov et al. teaches the use of poly(dimethylsiloxane) (PDMS) to form the channels, specifically to pattern the 3D cell-loaded hydrogel channels (Pg. 207, Materials and Methods section 2.5). Further, Trkov et al. teaches a co-culture system to study cell-cell interactions in a 3D fibrin hydrogel model, where hydrogel-encapsulated MSCs and ECs were placed in channels (Abstract). Trkov et al. teaches that micropatterning can be used to study the interactions between EC and MSC populations, as these cell populations are important in neovascularization (Pg. 212, Discussion) and demonstrates their culture model, which included channel implantation of cells, was able to successfully produce vascular networks of long, highly branched and interconnected tubular structures that resembled capillary networks and that these capillary like networks were stabilized and maintained (Pg. 211, Section 3.5).
However, as pointed out by the applicant on Pg. 7 of the remarks filed 10/10/2025, the hydrogel system taught by Trkov et al. is used in the context of studying functional interactions between cell types which requires keeping them wholly separated.
Taken together, the art fails to provide information on “a cell-free three-dimensional hydrogel culture medium comprising a channel wherein said channel comprises a mixture of endothelial cells (ECs) and mesenchymal stem cells (MSCs)” as recited in the instant claim.
Considering the variation in the use of hydrogel culture systems,s including their chemical composition, culture system physical characteristics (such as channel formation and cell placement with respect to the channel, and the lack of predictability provided by the specification and art for the full scope of the claimed genus, it is reasonable to conclude that Applicant did not possess the invention as claimed at the time of filing.
Thus, the specific embodiments regarding the breadth of the cell-free three-dimensional hydrogel culture medium sets forth new functions not previously disclosed as a contemplated embodiment in the present specification, nor one that was readily known and used in the art at the time of filing. Hence, is not clear that the Applicant was in possession of a genus of “a cell-free three-dimensional hydrogel culture medium comprising a channel wherein said channel comprises a mixture of endothelial cells (ECs) and mesenchymal stem cells (MSCs)” before the effective filing date of the claimed invention.
Please note: In order to further advance prosecution, the examiner recommends cancelling the new matter and amending the instant claims language to fully distinguish the invention of the instant application from the prior art by expressly reciting within the claims the characteristics of the system including, the hydrogel comprising a hollow channel (tissue channel), wherein the hollow channel is formed entirely through the hydrogel, using polydimethylsiloxane. The hydrogel is cell free is cell free in that does not comprise cells within the hydrogel ITSELF. A mixture of endothelial cells (ECs) and mesenchymal stem cells (MSCs) are placed within the hollow channel of the hydrogel. Thus, the system comprises cells within the channel following this placement. The system is incubated in a bioreactor circulating media with a defined inlet port to supply fresh media and an outlet port to discard used media. Claims 40-43, 46, 74-75, 77, 79-80, 83 and 87 will remain rejected until Applicant cancels all new matter.
Conclusion
Claims 40-43, 46, 74-75, 77, 79-80, 83 and 87 are rejected. No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KODYE LEE ABBOTT whose telephone number is (703)756-1111. The examiner can normally be reached M-F 8-5.
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, Maria G. Leavitt can be reached on (571) 272-1085. 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.
/KODYE LEE ABBOTT/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634