DETAILED ACTION
This action is in reply to papers filed 6/18/2024. Claims 1-15 are pending and examined herein.
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 .
Examiner’s Note
All paragraph numbers throughout this office action, unless otherwise noted, are from the US PGPub of this application US20240423928A1, Published 6/18/2024.
Claim Objections
Claims 3 and 6 are objected to because of the following informalities: Claim 3 is copied below. The term ‘the’ is missing between the words ‘wherein’ and ‘type’ in line 1.
PNG
media_image1.png
60
642
media_image1.png
Greyscale
Claim 6 is copied below. The term ‘being’ in line 2 is a present participle of the verb “to be” and implies an active step. Insofar as no step is performed in claim 6, removal of the term would be remedial.
PNG
media_image2.png
52
624
media_image2.png
Greyscale
Appropriate correction is required.
Claim Rejections - 35 USC § 102
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.
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Prior Art Rejection 1
Claim(s) 1, 4-6, 8 and 10-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chen et al. (Int J Mol Sci. 2022 Jun 20;23(12):6855.).
Chen et al. discloses Alzheimer’s disease is the most frequent form of dementia in aging population and is presently the world’s sixth largest cause of mortality. With the advancement of therapies, several solutions have been developed such as passive immunotherapy against these misfolded proteins, thereby resulting in the clearance. Within this segment, encapsulated cell therapy (ECT) solutions that utilize antibody releasing cells have been proposed with a multitude of techniques under development. Hence, in this study, Chen utilized a novel Microtube Array Membranes (MTAMs) as an encapsulating platform system with anti-pTau antibody-secreting hybridoma cells to study the impact of it on Alzheimer’s disease (as in claim 1 and claim 4). In vivo results revealed that in the water maze, the mice implanted with hybridoma cell MTAMs intracranially (IN) and subcutaneously (SC) (as in claim 13 and claim 14) showed improvement in the time spent the goal quadrant and escape latency (as in claim 15). In passive avoidance, hybridoma cell loaded MTAMs (IN and SC) performed significantly well in step-through latency. At the end of treatment, animals with hybridoma cell loaded MTAMs had lower phosphorylated tau (pTau) expression than empty MTAMs had. Combining both experimental results unveiled that the clearance of phosphorylated tau might rescue the cognitive impairment associated with AD (Abstract).
To make the MTAMs, Chen teaches PSF beads (as in claim 5) and polyethylene glycol were mixed until homogenous in a 7:3 mixture of N,N-dimethyl formamide and dichloromethane. Under ambient conditions, the resulting polymer solution was electrospun as a ‘shell solution’ with a ‘core solution’ comprised of polyethylene glycol and polyethylene oxide (Pg. 13, para. 1). Chen teaches the lumen dimensions of the electrospun PSF MTAMs were about 77.54 ± 4.3 µm × 35.64 ± 4.2 µm (height × width), with a lumen wall thickness of about 4.70 ± 0.3 µm, and a pore size of 167.75 ± 50 nm (as in claim 8, claim 10 and claim 11). Distribution size of the hybridoma that were loaded in the PSF MTAMs which averages around 14.4 ± 0.4 µm in diameter (as in claim 12). Regarding claim 6, Fig. 1M of Chen shows the MTAM has fibers that extended in a direction (Pg. 3, para. 2).
Accordingly, Chen anticipates the claimed invention.
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.
The factual inquiries 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.
Prior Art Rejection 2
Claim(s) 1-2,4-7, 9-13 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Cullen et al. (PgPub US20160250385A1, Published 9/1/2016) in view of Chen et al. (PgPub US20150342719A1, Published 12/3/2015), Mooney et al. (Future Oncol. 2014 Feb;10(3):401–415. (Year: 2014)), Chen et al. (US20220186416A1, Filed 3/30/2020), hereinafter referred to as Chen (b).
Regarding claim 1 and claim 13, Cullen et al. teach a method of culturing stem cells on an elongated tubular construct and implanting the resulting micro-tissue engineered neural network in a mammal to promote structural integration of the micro-tissue engineered neural network with the host brain tissue of the mammal, wherein the method restores an axonal connection damaged as a result of a condition selected from Alzheimer's disease and Parkinson's disease (as in claim 4 and claim 15) (Pg. 3, para. 41; Abstract).
However, Cullen et al. fails to teach the elongated tubular construct is a microtubular array membrane (as further in claim 1).
Before the effective filing date of the claimed invention, and with further regards to claim 1, Chen et al. teach a highly aligned and closely packed fiber assembly (~microtubular array membrane) that can be applied as a tube-in-tube structure and used as nerve guide conduit (Pg. 5, para. 62). Chen teaches the structure is seeded with neural stem cells (as in claim 2), whereby the cells are suspended in the scaffold and exposed to the appropriate molecular cues in 3-D. As taught by Mooney at Pg. 11 (para. 2) neural stem cells are 16 µm in diameter (as in claim 12). These cell-seeded electrospun hollow oriented (array) fiber assemblies are useful in tissue replacement protocols (Pg. 5, para. 63). According to this embodiment, tissue can be reconstituted in vitro and then implanted into a host in need thereof. Chen teaches the fibers are packed together to form the single layer (as in claim 9) (Pg. 3, para. 39) and the orientation of the hollow fibers is no larger than about +/−4° (as in claim 7) (Pg. 3, para. 41). Chen teaches the fibers have an average wall thickness of about 1 to about 5 μm (as in claim 10) (Pg. 3, para. 43).
However, Chen et al. fails to teach a material of the microtubular array membrane is Polysulfone (PSF) or a copolymer of Poly(lactic-co-glycolic acid) and Poly-L-lactic acid (PLGA-PLLA) (as in claim 5).
Before the effective filing date of the claimed invention, Chen (b) et al. teach a hollow electrospun fiber assembly, comprising multiple fibers having nanoscale hair like structures extended from inner surface thereof (Abstract). Chen (b) teaches the fibers have pores on the surface having a size ranging from 5 nm to 1 μm (as in claim 11) (Pg. 1, para. 8). Chen (b) teaches the fibers have a core-shell structure comprising polysulfone (as in claim 5) (Pg. 4, para. 48). Chen (b) teaches the fibers are perpendicularly arranged (as in claim 6) (Pg. 4, para. 42).
The combination of prior art cited above in all rejections under 35 U.S.C.103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1,148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 389, 82 USPQ2d 1385 (2007): "Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
In the present situation, rationales A and G are applicable. Before the effective filing date of the claimed invention, it would have been prima facie obvious to an artisan of ordinary skill to combine the teachings of Cullen et al., wherein Cullen teaches a method of culturing stem cells on an elongated tubular construct and implanting the resulting micro-tissue engineered neural network in a mammal to promote structural integration of the micro-tissue engineered neural network with the host brain tissue of the mammal, wherein the method restores an axonal connection damaged as a result of a condition selected from Alzheimer's disease and Parkinson's disease, with both Chen and Chen (b), wherein Chen teaches a microtubular array membrane suitable for use in tissue replacement protocols in vivo. That is, one of ordinary skill in the art would have found it prima facie obvious to substitute the generic tubular construct of Cullen et al. for the MTAM of Chen et al. for the purposes of treating Alzheimer’s or Parkinson’s disease, as set forth in Cullen. A reasonable expectation of success is present as Chen teaches the MTAM can be reconstituted in vitro and then implanted into a host in need thereof.
Thus, the teachings of the cited prior art in the obviousness rejection above provide the requisite teachings and motivations with a clear, reasonable expectation. The cited prior art meets the criteria set forth in both Graham and KSR.
Therefore, the claimed invention, as a whole, was clearly prima facie obvious.
Prior Art Rejection 3
Claims 3 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Cullen et al. (PgPub US20160250385A1, Published 9/1/2016) in view of Chen et al. (PgPub US20150342719A1, Published 12/3/2015), Mooney et al. (Future Oncol. 2014 Feb;10(3):401–415. (Year: 2014)), Chen et al. ( US20220186416A1, Filed 3/30/2020), hereinafter referred to as Chen (b) as applied to claims 1-2,4-7, 9-13 and 15 and further in view of Kihm et al. (PgPub US20100247499A1, Published 5/13/2014).
The teachings of Cullen et al., Chen et al., Mooney et al. and Chen (b) et al. are relied upon as detailed above. And although Cullen teaches use of stem cells, Cullen et al. fails to teach the stem cells are umbilical cord stem cells (as in claim 3).
Before the effective filing date of the claimed invention, Kihm et al. teach a method of reducing amyloid plaque formation or diminishing amyloid plaques in a patient, said method comprising administering to the subject a composition comprising a population of isolated human umbilical cord-derived cells such that amyloid plaque formation is reduced or diminished, wherein the isolated human umbilical cord-derived cells (as in claim 3) are obtained from human umbilical cord tissue substantially free of blood, wherein the isolated cells self-renew and expand in culture and do not express CD117 (see Kihm at claim 1; Pg. 2, para. 19; Pg. 5, para. 57). Kihm teaches cells in a semi-solid or solid carrier may also be prepared and surgical implanted at the site of neurotic plaque formation, which reasonably reads on intracranial implantation (as in claim 14) (Pg. 10, para. 111).
When taken with the teachings of Cullen et al., Chen et al., Mooney et al. and Chen (b) et al., wherein the combination teaches a method of culturing stem cells on microtubular array membrane and implanting the resulting micro-tissue engineered neural network in a mammal to promote structural integration of the micro-tissue engineered neural network with the host brain tissue of the mammal, wherein the method restores an axonal connection damaged as a result of a condition selected from Alzheimer's disease and Parkinson's disease, one of ordinary skill in the art would have found it prima facie obvious to substitute the generic stem cells of Cullen et al. with the umbilical cord derived mesenchymal stem cells of Kihm et al. because Kihm teaches administration of such cells reduced amyloid plaque formation in an Alzheimer’s patient.
Therefore, the claimed invention, as a whole, was clearly prima facie obvious.
Prior Art Rejection 4
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Cullen et al. (PgPub US20160250385A1, Published 9/1/2016) in view of Chen et al. (PgPub US20150342719A1, Published 12/3/2015), Mooney et al. (Future Oncol. 2014 Feb;10(3):401–415. (Year: 2014).), Chen et al. (US20220186416A1, Filed 3/30/2020), hereinafter referred to as Chen (b) as applied to claims 1-2,4-7, 9-13 and 15 and further in view of Chew et al. (Membranes (Basel). 2021 Sep 27;11(10):732.).
The teachings of Cullen et al., Chen et al., Mooney et al. and Chen (b) et al. are relied upon as detailed above. And although Chen teaches a microtube array membrane, Chen et al. fails to teach the microtubular array membrane ranges from 80 μm to 120 μm in height and from 40 μm to 60 μm in width (as in claim 8).
Before the effective filing date of the claimed invention, Chew et al. taught MTAMs that were high porous, high degree of alignment, which is extremely critical to induce directional proliferation of cells, mechanically sound, good flexibility, and being easily manipulated (Pg. 3, para. 3). Chew teaches Image J analysis revealed the dimensions of the microstructures to be 57.7 ± 2.8 μm (w) × 72.5 ± 3.6 μm (h) which reasonably reads on 80 μm to 120 μm in height and from 40 μm to 60 μm in width (as in claim 8) (Pg. 6 ‘Results’).
When taken with the teachings of Cullen et al., Chen et al., Mooney et al. and Chen (b) et al., wherein the combination teaches a method of culturing stem cells on microtubular array membrane and implanting the resulting micro-tissue engineered neural network in a mammal to promote structural integration of the micro-tissue engineered neural network with the host brain tissue of the mammal, wherein the method restores an axonal connection damaged as a result of a condition selected from Alzheimer's disease and Parkinson's disease, one of ordinary skill in the art would have found it prima facie obvious to substitute the MTAM of Chen for the MTAM of Chew et al. because Chew teaches their MTAM possessed a high degree of alignment, was mechanically sound, good flexibility, and being easily manipulated. For the purposes of in vivo transplantation, one of ordinary skill in the art would have the substitution prima facie obvious.
Thus, the combination would have been prima facie obvious.
Authorization to Initiate Electronic Communications
The examiner may not initiate communications via electronic mail unless and until applicants authorize such communications in writing within the official record of the patent application. See M.P.E.P. § 502.03, part II. If not already provided, Applicants may wish to consider supplying such written authorization in response to this Office action, as negotiations toward allowability are more easily conducted via e-mail than by facsimile transmission (the PTO's default electronic-communication method). A sample authorization is available at § 502.03, part II.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TITILAYO MOLOYE whose telephone number is (571)270-1094. The examiner can normally be reached Working Hours: 5:30 a.m-3:00 p.m. M-F. Off first Friday of biweek..
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, Peter Paras can be reached on 571- 272-4517. 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.
/TITILAYO MOLOYE/Primary Examiner, Art Unit 1632
Prosecution Insights