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 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.
Claims 1-4,7-16,18, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Yamanaka et al and further in view of Bowles et al.
Yamanaka et al. teaches a method for transplanting an artificially created transplant material comprising an organ into which a foreign substance (e.g., nephron progenitor cells (NPCs)) has been injected. An embryonic organ (mouse metanephros aka “MN”) is removed from a fetus-animal body and the foreign substance is injected into the removed organ using a needle. The resulting transplant material is the transplanted. Specifically, “First, we injected GFP- or DsRed-NPCs plus DT below the renal capsule of an isolated Six2-iDTR MN (Fig. 7A-B) and then transplanted the Six2-iDTR MN containing DT-uneffective exogenous NPCs into the proximity of the aorta of B6 mice.” (Results section, paragraph “In vivo renal regeneration by the cell elimination system.”). Additionally, “…a glass needle filled with cells was inserted into the renal membrane from the renal hilus, and the cells were injected… the needle was removed when the nephrogenic zone under the renal capsule was filled… MNs were then subjected to organ culture or were transplanted into adult mice.” (Methods section, paragraph “Injection of NPCs into the nephrogenic zone”). Importantly, GFP-NPCs or DsRed-NPCs are collected from E13.5 mice or mice expressing DsRed, and they are injected into MNs harvested from B6 or Six2-iDTR E13.5 embryos (see methods section paragraphs “NPCs derived from enzymatic dissociation of MNs” and “Injection of NPCs into the nephrogenic zone” respectively).
Furthermore, Yamanaka et al. also teaches a xenotransplantation variation of the aforementioned method wherein rat NPCs are injected into mouse MNs. Specifically, “By transplanting rat GFP-NPCs into the Six2-iDTR MN of mice, we examined interspecific renal regeneration (Fig. 8f, schematic). As a result, Six2-positive cells of rats were observed in the CM of mice. In these Six2-positive cells, mouse-derived NPCs had been eliminated with DT, thus providing support for the integration of rat-derived NPCs into the mouse-derived CM and ureteric tip (Fig. 8a, left, 8b, and 8c).” (Results section, paragraph “Generation of interspecies chimeric whole nephrons”).
Yamanaka does not expressly disclose bringing the removed organ into contact with a member having plasticity for positioning the organ prior to injection. They also do not expressly disclose selecting a needle entry surface based on the specific spatial relationship between the entry surface and the injection target zone as recited in claim 2.
Bowles et al. teaches positioning small biological tissues by immobilizing the tissue within a deformable gel material. Specifically, Bowles discloses that, "The technique described in this protocol allows the user to position small tissues in the optimal orientation … by first immobilizing the tissue in an agarose/gelatin cube." (Abstract). Bowles further teaches that "an agarose/gelatin drop is created to surround the tissue" and that "the tissue can be orientated as per the user's preference in the drop before it sets." (Abstract). Therefore, Bowles expressly teaches embedding a small tissue in a deformable agarose/gelatin material for the purpose of stabilizing and positioning an organ in a desired orientation to aid in subsequent manipulation.
Additionally, the instant specification defines the "surface immediately above the injection target zone" as "a surface closest to the injection target zone on a surface of the organ," and the "surface near the injection target zone" as "a surface present on the same side as the injection target zone with respect to a center of the organ." (Instant application, paragraph 0053.). Therefore, under the broadest reasonable interpretation consistent with the instant specification, the limitations of claim 2 requiring that the injection be performed from a surface "immediately above or near" the injection target zone merely describes the relative positional relationship between the needle entry surface and the location where the injected substance is deposited.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify the method(s) of producing a transplant material (using rat NPCs or mouse NPCs) and then transplanting it as disclosed by Yamanaka by incorporating the tissue-positioning and immobilization technique taught by Bowles. Immobilization of small biological tissues within a deformable gel improves control and orientation during tissue manipulation. Applying this same tissue-positioning technique to the embryonic metanephros of Yamanaka would improve stabilization and orientation of the small organ during the (rat and/or mouse) NPC microinjection procedure. Therefore, claim 1 (organ construction method) and claim 20 (transplant method) are rendered obvious.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to orient the embryonic metanephros of Yamanaka as taught by Bowles before performing the needle injection. Stabilizing and orienting the small metanephros permits selection of an accessible surface for introducing the needle into the nephrogenic zone while improving injection accuracy, reducing unnecessary tissue penetration, and facilitating manipulation of the organ. Selecting an entry surface immediately above or otherwise near the target injection zone would have represented no more than a predictable optimization of Yamanaka's known microinjection procedure. Therefore, claim 2 is rendered obvious.
In addition, under the broadest reasonable interpretation consistent with the instant specification, the claimed “dense structure” recited in claim 10 includes, “a dense structure is preferable that is difficult for a liquid (preferably, a liquid containing the foreign substance) to penetrate as compared with the luminal portion of the organ (for example, the luminal organ), the hilus portion, or the like, and a structure in which a tissue (for example, a connective tissue) or cells (for example, mesenchymal cells) are densely filled is more preferable…” (Instant specification paragraph 30). Because Yamanaka expressly teaches delivering donor-derived cells into the nephrogenic zone directly under the renal capsule (See Fig. 1F), the needle necessarily passes through the same densely packed mesenchymal tissue identified in the instant specification as the preferred dense structure.
The present disclosure also reads on dependent claims 3-4, and 7-12. The disclosure specifies that MNs are harvested from (B6 or Six2-iDTR) E13.5 embryos (claim 3-fetus body), NPCs harvested from either rat or mouse embryos are injected into the mouse MNs (claim 4-xenotransplantation), that the agarose/gelatin drop “surrounds” the tissue (claim 7-portion is embedded and claim 8-gel), and a needle is used to inject (claim 9-needle-shaped) NPCs harvested from genetically distinct (CAG-GFP/dsRED) mice or rates (claim 11-derivded from different animal) into the MN nephrogenic zone (claim 12-target is nephrogenic zone).
Furthermore, Yamanaka et al’s disclosure and performance of the aforementioned method inherently results in a composition/material comprising an organ (mouse MN) that has been injected with cells derived from a location other than the organ (rat NPCs) that is suitable for xenotransplantation (mouse MN injected with rat NPCs) (See Figures 1-8). This reads on claim 13 (transplant material), claim 14 (injected with foreign cells), and claim 16 (xenotransplantation). Claim 15 and claim 18 are process limitations that impart no known and/or disclosed structure on the product of claim 13. Therefore, claim 15 and claim 18 hold no patentable weight.
Claims 5-6,17,19 are rejected under 35 U.S.C. 103 as being unpatentable over Yamanaka et al and Bowles et al as applied to claim 1 above, and further in view of Yokote et al and Wei et al.
Yamanaka et al and Bowles et al. teach the method of producing, and the composition itself, defined as a transplant material in claim 1.
Yamanaka does not expressly disclose subjecting the removed organ to vitrification freezing, does not teach coating/covering the organ and the injection site in a gelatinous solution prior to vitrification/freezing. Yamanaka also does not disclose an using organ removed from a pig.
Yokote et al. teach vitrification freezing of removed metanephroi. Specifically, "Primordial pig metanephroi were dissected under a stereomicroscope ... and some were cryopreserved. A preliminary experiment confirmed the absence of significant differences in the growth of vitrified and nonvitrified pig metanephroi transplanted into mice." (Results section, "Syngeneic Transplantation of Pig Metanephroi").
Wei S et al teaches the use of hydrogel coated needles to inject organs. They show the hydrogels result in the rapid attenuation of bleeding from the site.
It would be obvious to a person of ordinary skill in the art, before the effective filing date, to use hydrogel coated needles taught by Wei S et al in the injection of the gel encased organ of Yamanaka et al and Bowles et al. The coated needles result in the deposition of hydrogels at/in injection site, which helps attenuate bleeding and facilitates healing.
It would be obvious to a person of ordinary skill in the art, before the effective filing date, to take the injected organ of above, which has been modified by providing "an agarose/gelatin drop is created to surround the tissue" as taught by Bowles et al. and to incorporate the step of metanephroi vitrification as taught by Yokote et al. Vitrification ensures organ vitality is maintained throughout the entire process from growth, assembly, transport and transplantation, all of which constitute an inherently asynchronous process. Therefore, applying Yokote's vitrification technique to the isolated metanephros constitutes the predictable use of a known preservation methods for their established purpose of preserving biological organs. Therefore, claim 5, claim 6, claim 19 are rendered obvious.
Additionally, it would have been obvious to a person of ordinary skill in the art, before the effective filing date, to modify the transplant material of Yamanaka and Bowles by trading a porcine metanephros as taught in view of Yokote et al for the mouse metanephros of Yamanaka. Somone of ordinary skill in the art would be motivated to utilize a porcine metanephros in place of a mouse-derived one because pigs are recognized as superior donor species for human xenotransplantation applications. Therefore, claim 17 is rendered obvious.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Adam M Smith whose telephone number is (571)272-7517. The examiner can normally be reached Monday- Friday 10:30AM-5PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Tracy Vivlemore can be reached at (571) 272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Tracy Vivlemore/ Supervisory Primary Examiner, Art Unit 1638
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