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 08/21/2025.
Claim 1 has been amended, claims 7-8 and 10 have been canceled and claims 11 and 12 are newly added as set forth in the claim set filed 08/21/2025. Claims 1 and 11 are independent.
Therefore, claims 1, 11 and 12 are pending and have been considered on the merits.
Priority
This application is a 371 of PCT/JP2017/024246 filed 06/30/2017 which claims a foreign priority to JP2016-132075 filed 07/01/2016.
Therefore, the earliest possible priority date for the instant application is July 1, 2016.
Withdrawn objections/ Rejections in response to Applicants’ arguments or amendments
Claim Rejections - 35 USC § 102
The rejection of claims 1, 7, 9 and 10 under 35 U.S.C. 102(a)(1) as being anticipated by Wakao (Cells 2012, 1, 1045-1060; previously cited) as evidenced by Yoshida (U.S. Patent No. 9,844,570; previously cited) and Iseki (Cell Transplantation, Vol. 26, pp. 821–840, 2017; IDS Reference) is withdrawn.
Applicant’s arguments and amendments filed 08/21/2025 have been considered and are persuasive. In particular, Applicant’s arguments regarding the evidence of Kuroda wherein Figure 4 is better explained as local injection are persuasive in overcoming the anticipation rejection.
Claim Rejections - 35 USC § 103
The rejection of claims 1, 7, and 10 under 35 U.S.C. 103 as being unpatentable over Kaneko et al. (March 2015. Research Project for Control Measures for Hepatitis: 1-11; IDS Reference AM filed on 04/01/2019) as evidenced by Yoshida (U.S. Patent No. 9,844,570; previously cited in PTO-892) and newly evidenced by Iseki (Cell Transplantation, Vol. 26, pp. 821–840, 2017; IDS Reference) in view of Wakao (Cells 2012, 1, 1045-1060; previously cited) is rendered moot in view of applicants’ cancelation of claims 7 and 10.
A response to Applicant’s arguments with regard to a withdrawn rejection is moot.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.
The rejection of claims 1 and 8 under 35 U.S.C. 103 as being unpatentable over Kaneko et al. (supra) as evidenced by Yoshida (supra) and Iseki (supra) in view of Wakao (supra) as applied to claims 1, 7 and 10 above, and in further view of Young et al. (US2013/0071357; previously cited in PTO-892) is rendered moot in view of Applicants’ cancelation of claim 8.
Double Patenting
The rejections of claims 1, 8 and 10 on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of copending Application No. 18/005,537 in view of Wakao and Young are withdrawn.
The rejection of claims 1, 7, and 10 as being unpatentable over claims 1-7 of copending Application No. 18/005,537 in view of Wakao (Cells 2012, 1, 1045-1060) as evidenced by Yoshida (U.S. Patent No. 9,844,570; previously cited in PTO-892) and Iseki (Cell Transplantation, Vol. 26, pp. 821–840, 2017; IDS Reference) has been withdrawn.
The copending application ‘537 amendment filed 10/27/2025 renders the claims patentably distinct due to the invention becoming a method for motor neuron disease instead of a preparation of MUSE cells.
Maintained objections/ Rejections in response to Applicants’ arguments or amendments
Claim Rejections - 35 USC § 103
Claim 1 remains rejected under 35 U.S.C. 103 as being unpatentable over Kaneko et al. (March 2015. Research Project for Control Measures for Hepatitis: 1-11; IDS Reference AM filed on 04/01/2019) as evidenced by Yoshida (U.S. Patent No. 9,844,570; previously cited in PTO-892) and Iseki (Cell Transplantation, Vol. 26, pp. 821–840, 2017; IDS Reference) in view of Wakao (Cells 2012, 1, 1045-1060; previously cited) and further view of Young et al. (US2013/0071357; previously cited in PTO-892).
This rejection has been modified in response to Applicant’s amendments filed 08/21/2025.
Regarding claims 1, Kaneko et al. administered Muse cells (i.e. SSEA-3+ CD105+ pluripotent stem cells obtained from mesenchymal tissue) into the tail vein (i.e. intravenously) of a mouse in a model of liver fibrosis in order to treat the organ. The study of the chronic liver fibrosis disorder demonstrated significant suppression of fibrosis (1st page of Translation).
As evidenced by Yoshida et al., Muse cells are SSEA-3 and CD-105 positive and show negative expression for CD117, CD146, NG2, CD34, vWF and CD271 (Col. 8, lines 18-44). Furthermore, Yoshida teaches the Muse cells inherently have low or absent telomerase activity, ability to differentiate into embryonic endoderm, ectoderm, and mesoderm germ layers, with absence of neoplastic proliferation; and (v) ability to self-renew (Claim 1; Col. 8, lines 45-54). These muse cells are not reprogrammed or induced pluripotent cells (i.e. created in vitro to induce pluripotency).
Regarding the limitation of regenerating the organ through lysis of fibrotic tissue, Iseki teaches that Muse cells inherently produce matrix malloproteases (MMPs) which are involved in fibrolysis and/or suppression of fibrosis (p. 831, 1st column; p. 835, 2nd column). Therefore, lysis of fibrotic tissue is an inherent function of Muse cells themselves, rendering obvious treatment of fibrosis.
Wakao et al taught that some Muse cells, upon administration, were present “in the lung and spleen, but, interestingly, the majority of Muse cells integrated into damaged tissues and not into intact tissues” (p. 1053, para 4.). Muse cells naturally integrate into damaged tissues, as they are perceptive of damaged sites and contribute to tissue reconstruction via their ability to differentiate into tissue specific cells (p. 1053).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date that the Muse cells of Kaneko which treat liver fibrosis would be capable of treating disorders of damaged tissue present in organs such as the lung as taught by Wakao, with a reasonable expectation of success. An artisan would have been motivated to utilize Muse cells in damaged tissue of various organs (i.e. the lung) as Wakao teaches Muse cells naturally integrate into damaged tissues, as they are perceptive of damaged sites and contribute to tissue reconstruction via their ability to differentiate into tissue specific cells.
However, Kaneko, Wakao, Iseki and Yoshida do not teach the treatment of lung fibrosis.
Young et al. teaches administering pluripotent stem cells isolated from blood (i.e. mesenchymal tissue from a body) intravenously which have SSEA-3+ cell markers in order to treat pulmonary diseases such as Interstitial Pulmonary Fibrosis (IPF; i.e. lung fibrosis) (Abstract, para. 0017, 0064; claim 87). Young discloses that the pluripotent stem cells can be utilized to treat neuropathies, skeletal muscle injuries, disorders of the skin as well as lung conditions (para. 0064).
Prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to utilize the Muse cells of Kaneko, Yoshida and Wakao for the purpose of treating lung fibrosis with a reasonable expectation of success. An artisan would be motivated to do so as Young teaches SSEA-3+ pluripotent stem cells are utilized in methods of treating disorders such as Interstitial Pulmonary Fibrosis.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
New grounds of objections/ Rejections in response to Applicants’ arguments or amendments
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 11 and 12 are newly rejected under 35 U.S.C. 103 as being unpatentable over Kaneko et al. (March 2015. Research Project for Control Measures for Hepatitis: 1-11; IDS Reference AM filed on 04/01/2019) as evidenced by Yoshida (U.S. Patent No. 9,844,570; previously cited in PTO-892) and Iseki (Cell Transplantation, Vol. 26, pp. 821–840, 2017; IDS Reference) in view of Wakao (Cells 2012, 1, 1045-1060; previously cited)
This rejection has been necessitated by Applicant’s amendments filed 08/21/2025.
Regarding claims 11 and 12, Kaneko et al. teaches administered Muse cells (i.e. SSEA-3+ CD105+ pluripotent stem cells obtained from mesenchymal tissue) into the tail vein (i.e. intravenously) of a mouse in a model of liver fibrosis in order to treat the organ. The study of the chronic liver fibrosis disorder demonstrated significant suppression of fibrosis (1st page of Translation).
As evidenced by Yoshida et al., Muse cells are SSEA-3 and CD-105 positive and show negative expression for CD117, CD146, NG2, CD34, vWF and CD271 (Col. 8, lines 18-44). Furthermore, Yoshida teaches the Muse cells inherently have low or absent telomerase activity, ability to differentiate into embryonic endoderm, ectoderm, and mesoderm germ layers, with absence of neoplastic proliferation; and (v) ability to self-renew (Claim 1; Col. 8, lines 45-54). These muse cells are not reprogrammed or induced pluripotent cells (i.e. created in vitro to induce pluripotency).
Regarding the limitation of regenerating the organ through lysis of fibrotic tissue, Iseki teaches that Muse cells inherently produce matrix malloproteases (MMPs) which are involved in fibrolysis and/or suppression of fibrosis (p. 831, 1st column; p. 835, 2nd column). Therefore, lysis of fibrotic tissue is an inherent function of Muse cells themselves.
However the combined teachings of Kaneko, Yoshida and Iseki do not teach the treatment of fibrosis utilizing pluripotent stem cells wherein the fibrosis is skin fibrosis.
Wakao teaches that MSCs comprising the Muse cells (i.e. pluripotent stem cells) naturally home to damaged sites and naturally differentiate into hepatocytes and keratinocytes or epidermal cells, integrating and contributing to tissue repair (p. 1046, 2nd-3rd paragraphs). Wakao further teaches that upon administration, the cells naturally home to damaged sites (i.e. sites of fibrosis) and can integrate as functional cells into damaged tissue and differentiate into endodermal or ectodermal according to the site of integration (p. 1053, Tissue Repairing Function of Muse Cells). This is particularly reduced to practice in the animal model of Figure 4 wherein the Muse cells are administered via tail vein (i.e. intravenous administration) for internal disorders and locally for skin injury models.
Prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to have modified the method taught by Kaneko, Yoshida and Iseki with the method of Wakao al to arrive at the instantly claimed method with a reasonable expectation of success. The ordinary artisan would have been motivated to make the modification because said modification would have resulted in a method having the added advantage of treating skin fibrosis or skin injury as explicitly taught by Wakao. In addition, it would have been obvious to the ordinary artisan that the known techniques of Wakao et al could have been applied to the method of Kaneko, Yoshida and Iseki et al with predictable results because the known techniques of Wakao et al predictably results in methods useful treatment of for skin injury.
Regarding the limitations of the patient having claim 11 recites “wherein skin collagen content is decreased in the skin of the patient” and claim 12 recites “wherein dermal thickness is decreased in the skin of the patient,” as these are interpreted to be results of the active method steps of claim 11, they are rendered obvious by the combination of Keneko and Wakao. Each and every method step is taught and therefore, the same method steps yield the same predictable results with a reasonable expectation of success.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Response to Applicants’ Arguments as they apply to rejection under 35 USC § 103 in relation to the teachings of Keneko and Wakao.
Applicant’s arguments filed 08/21/2025 have been considered, however they are not persuasive.
Applicant argues the same points of the 102 Wakao wherein “the method did not treat skin fibrosis but rather administration following removal of skin. Wakao also does not disclose treating lung fibrosis. The Office Action asserts that a skilled artisan would have substituted one known element for another to yield predictable results. However, because Wakao does not teach what the Office Action asserts that it does (see discussion rebutting the Q 102 rejection above) the premise this assertion is based on is flawed. Therefore, the rejections under 35 U.S.C§103 should be withdrawn.” Moreover, “The cited art does not identify these therapeutic benefits as a goal and certainly provides no basis to expect success in achieving them.”
Examiner does not utilize the references in the same manner in the 103 rejection than the 102. The 102 rejection has been withdrawn due to the sole teaching of Wakao, however the combination of Keneko with Wakao allows for a reasonable expectation of success in yielding predictable results and the results of the new feature limitations. As discussed above, “animal model of Figure 4 wherein the Muse cells are administered via tail vein (i.e. intravenous administration) for internal disorders and locally for skin injury models” does not indicate that lung or skin fibrosis is treated explicitly, however skin injury as evidenced, is accompanied by skin fibrosis. Though the methods in the cited references within Wakao for review are for skin regrowth and defect, the suggestion of “skin injury” would encompass that of skin fibrosis. There is suggestion to apply to the skin, the treatment of fibrosis would be another result of the treatment of skin injury. Iseki teaches that Muse cells inherently produce matrix malloproteases (MMPs) which are involved in fibrolysis and/or suppression of fibrosis (p. 831, 1st column; p. 835, 2nd column). Therefore, lysis of fibrotic tissue is an inherent function of Muse cells themselves which is effective in treating organ fibrosis. Therefore, the teaching of Keneko that an artisan would administer Muse cells to a subject with fibrosis would result inherently that the cells would exhibit fibrolytic activity within the organ.
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 1, 11 and 12 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 1 recites “wherein incidence of increased respiration rate is reduced in the patient.”
Claim 11 recites “wherein skin collagen content is decreased in the skin of the patient.”
Claim 12 recites “wherein dermal thickness is decreased in the skin of the patient.”
It is unclear whether these properties are present in the patient prior to the treatment or as a result of the treatment.
This renders the claims indefinite.
Conclusion
No claims are allowed.
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.
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/ALEXANDRA F CONNORS/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634