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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 2/12/2026 has been entered.
Claims 1-41, of record 2/20/2026, are pending. Claims 1-23 and 25-26 remain withdrawn. Claim 24 is amended. Claims 35-41 are newly added.
Status of Prior Rejections/Response to Arguments
RE: Objection to the drawings:
The submission of a replacement drawing is effective to obviate the objection. The objection is withdrawn.
RE: Rejection of claims 24 and 27-31 under 35 U.S.C. 103 over Kang et al. (Experimental Neurology, 2003), evidenced by K. Chen et al. (Oncotarget, 2016) and Jiang et al. (Mediators of Inflammation, 2010), in view of Fauzi et al. (Journal of Stem Cells & Regenerative Medicine, 2016), Dykstra et al. (Stem Cells Translational Medicine, 2017), and B. Chen et al. (Journal of Neuroscience Research, 2012):
RE: Rejection of claims 24 and 27-32 under 35 U.S.C. 103 over Kang et al. (Experimental Neurology, 2003), evidenced by K. Chen et al. (Oncotarget, 2016) and Jiang et al. (Mediators of Inflammation, 2010), in view of Fauzi et al. (Journal of Stem Cells & Regenerative Medicine, 2016), Dykstra et al. (Stem Cells Translational Medicine, 2017), and B. Chen et al. (Journal of Neuroscience Research, 2012), further in view of Kondo et al. (Nature, 2015):
RE: Rejection of claims 24, 27-28, 30-31, and 33-34 under 35 U.S.C. 103 as being unpatentable over Kang et al. (Experimental Neurology, 2003), evidenced by K. Chen et al. (Oncotarget, 2016) and Jiang et al. (Mediators of Inflammation, 2010), in view of Fauzi et al. (Journal of Stem Cells & Regenerative Medicine, 2016), Dykstra et al. (Stem Cells Translational Medicine, 2017), and B. Chen et al. (Journal of Neuroscience Research, 2012), further in view of Palejwala et al. (Surgical Neurology International, 2014):
The applicant asserts that:
Kang et al. teach stromal cells, which are not necessarily stem cells, and that the stromal cells are differentiated to neural cells prior to transplantation (Applicant Remarks, page 12).
No reasonable expectation of success is provided in modifying the cells of Kang et al. to not induce neural differentiation prior to transplantation, which would alter its principle of operation, or to include a stromal vascular fraction (Applicant Remarks, page 13-14).
Dykstra et al. teach the use of isolated stromal vascular fraction components and do not teach or render obvious the use of a stromal vascular fraction concentrate (Applicant Remarks, page 12).
Dykstra et al., in teaching that challenges remain for the application of the stromal vascular fraction and its components, contradict a reasonable expectation of success in the therapeutic use of the whole stromal vascular fraction (Applicant Remarks, page 14-15).
The level of ordinary skill in the art has not been indicated or discussed (Applicant Remarks, page 15-16).
The applicant’s arguments have been considered but are not found persuasive. As an initial matter, the arguments concerning the reference Kang et al. and its combination with other references largely hinge on misinterpretation of the teachings of Kang et al. Kang et al. teach that the adipose-derived stromal cells were able to be differentiated in vitro to neural cells (See page 356, col. 2, full ¶2), which implies that these stromal cells are stem cells. The hATSCs are confirmed as being mesenchymal stem cells (See page 362, col. 2, ¶1). Kang et al. do not teach differentiation of the stromal cells prior to transplantation; markers expressed by in vitro-differentiated cells were compared to those expressed by engrafted cells (See fig. 2-3). The passage in the Abstract cited by the applicant (“Following neural induction, hATSCs changed toward neural morphology and… were injected into the lateral ventricle of the rat brain”) is in fact two separate sentences (“Following neural induction, hATSCs changed toward neural morphology and displayed expression of MAP2 and GFAP. hATSCs, which were labeled with LacZ adenovirus, were injected into the lateral ventricle of the rat brain”). There is no indication, either in the abstract or in the body of the text, that the neurally-induced hATSCs of the first sentence and the injected hATSCs of the second sentence are the same cells or that neural differentiation should be done prior to transplantation. Further, as the hATSCs are not differentiated prior to administration in the method of Kang et al., modification of the method with the teachings of Dykstra et al. would not change its principle of operation.
Regarding the argument that Dykstra et al. do not teach or suggest the use of a whole vascular fraction, much less a stromal vascular fraction concentrate, or a reasonable expectation of success in doing so, the explicit focus of the review is the stromal vascular fraction (See page 1096, col. 2, full 1 and page 1097, col. 1, ¶1). Because use of the stromal vascular fraction in therapy is relatively new, Dykstra et al. state that “one can attempt to define its real therapeutic potential by separately assessing the potential of each cell component that has been identified within the SVF to date” and that “encouraging studies mentioned here describing the isolation and characterization of SVF-derived HSCs, EPCs and pericytes attest to significant therapeutic promise. Hence, are we underestimating the therapeutic potential of SVF?” (See page 1100, col. 2, ¶1). These passages indicate that Dykstra et al. anticipate that the stromal vascular fraction be utilized as a whole and with the potential effect of being as beneficial, therapeutically, as the sum of its cell type parts. Individual cell types are addressed as a means of understanding the potential effects of the stromal vascular fraction, not necessarily as a recommendation that the isolated cells be used instead of the entire fraction. Additionally, in pointing out knowledge gaps surrounding the stromal vascular fraction, Dykstra et al. do not contradict its usage for therapy, but merely present a balanced discussion of a nascent therapy.
It is also noted that amended limitation “a stromal vascular fraction concentrate” is not defined by the instant specification and must therefore be considered under its broadest reasonable interpretation. A “concentrate” is generally considered to constitute a quantity (e.g., of cells) that is reduced in volume. Because stromal vascular fractions are produced from the enzymatic digestion of adipose tissue or mechanical isolation of the cells therein, followed by separation and pelleting of the cells by centrifugation (See Dykstra et al., page 1096, col. 2, full ¶1; page 1097, col. 1, ¶1; page 1098, col. 2, full ¶2; see also Oberbauer et al. (cited by Dykstra et al. at page 1097, col. 2, full ¶1), page 1, col. 2, full ¶1; page 3, col. 2, full ¶1; and fig. 1), a stromal vascular fraction is itself a concentrate. The amended limitation is thus rendered obvious by Dykstra et al.
Regarding the reasonable expectation of success required for a prima facie showing of obviousness, no specific language is required by the Office to articulate this. The “reasonable expectation of success” requirement refers to the likelihood of success” in combining or modifying prior art disclosures to meet the limitations of the claimed invention. As stated in MPEP 2143.02, a reasonable expectation of success can be implicitly shown via the prior art teachings or as part of the obviousness analysis. For instance, Fauzi et al. teach the use of an Ommaya reservoir for intraventricular administration of stem cells, which implies the successful wider application of the reservoir for compositions comprising stem cells, such as a stromal vascular fraction.
Regarding the level of ordinary skill in the art, this is implicit in the prior art, which requires conversance and expertise in such areas as surgery, physiology, and cell and molecular biology. Specifying a particular level of skill is not necessary where the prior art itself reflects an appropriate level. See MPEP 2141.03(II).
The rejections are maintained in modified form to address amended limitations.
RE: Rejection of claims 24, 30, and 33-34 on the ground of nonstatutory double patenting over claims 1-2, 4-5, and 7 of U.S. Patent No. 11730767:
The terminal disclaimer filed on 2/12/2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of US Patent No. 11730767 has been reviewed and is accepted. The terminal disclaimer has been recorded. The rejection is withdrawn.
New/Maintained Objections/Rejections
Claim Objections
Claims 39 and 41 are objected to because of the following informalities:
In line 2 of claim 39, the word “cell” should be inserted in front of “progenitors”.
In line 4 of claim 41, “Lrg5” should be replaced with “Lgr5”.
Appropriate correction is required.
Claim Interpretation
Claim 24 requires the limitation “a stromal vascular fraction concentrate”, which is not defined by the instant specification. A “concentrate” is generally considered to constitute a quantity (e.g., of cells) that is reduced in volume. Because stromal vascular fractions are produced from the enzymatic digestion of adipose tissue or mechanical isolation of the cells therein, followed by separation and pelleting of the cells by centrifugation (See Dykstra et al., page 1096, col. 2, full ¶1; page 1097, col. 1, ¶1; page 1098, col. 2, full ¶2; see also Oberbauer et al. (cited by Dykstra et al. at page 1097, col. 2, full ¶1), page 1, col. 2, full ¶1; page 3, col. 2, full ¶1; and fig. 1), a stromal vascular fraction is itself a concentrate. The broadest reasonable interpretation of “a stromal vascular fraction concentrate” is therefore considered to be any stromal vascular fraction.
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.
Claims 24, 27-31, 36, 38, and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Kang et al. (Experimental Neurology, 2003), evidenced by K. Chen et al. (Oncotarget, 2016) and Jiang et al. (Mediators of Inflammation, 2010), in view of Fauzi et al. (Journal of Stem Cells & Regenerative Medicine, 2016), of record, Dykstra et al. (Stem Cells Translational Medicine, 2017), and B. Chen et al. (Journal of Neuroscience Research, 2012).
Regarding claims 24, 27-28, 30, 36, and 40: Kang et al. teach transplantation of adipose-derived stromal cells (which read on “adipose-derived stem cells” and “neural differentiation of the adipose-derived stem cells is not induced prior to delivery”) from a stromal vascular fraction in rats with ischemic brain injury (See Abstract; page 356, col. 2, full ¶1; and page 357, col. 2, full ¶3). The cells were transduced with adenovirus vectors for expression of β-galactosidase or BDNF (which reads on “genetically modified” and “a pharmaceutical”) (See page 357, col. 2, full ¶3). The cell suspension was injected directly into the lateral ventricle (which reads on “a ventricular system of a brain”) (See page 357, col. 2, full ¶3).
Kang et al. do not expressly teach injection of the cells via an implanted reservoir, use of a stromal vascular fraction concentrate, or activation of Wnt.
Fauzi et al. teach the transplantation of autologous bone marrow-derived mesenchymal stem cells via Ommaya reservoir (which reads on “implanted reservoir”) for treating hemorrhagic stroke (See Abstract). The cells were injected intraventricularly using a syringe (which reads on “injector”) (See page 101, col. 2, ¶2).
Dykstra et al. teach that the stromal vascular fraction (which reads on “a stromal vascular fraction concentrate”) can be used therapeutically in regenerative medicine and that, in addition to adipose-derived stem cells, it comprises other cell types, such as pericytes, leukocytes, and endothelial progenitor cells, that modulate inflammation and vascularization (See Abstract and fig. 1). Stromal vascular fraction therapies can be autologous in nature (See page 1105, col. 1, ¶1).
B. Chen et al. teach that BDNF triggers the Wnt/β-catenin signaling pathway in neural stem cells and that the effect of BDNF is blocked by a Wnt signaling inhibitor (See Abstract and fig. 6-8).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Kang et al. to comprise use of an Ommaya reservoir, such as is taught by Fauzi et al., in a system for transplanting stem cells. One would be motivated to make this modification because Fauzi et al. teach that the Ommaya reservoir enables safe, effective, and repeated intraventricular transplantation of autologous stem cells (See Abstract). There would be a reasonable expectation of success in making this modification because the cells of Kang et al. could be readily delivered via Ommaya reservoir.
It also would have been obvious to one of ordinary skill to administer the modified stromal cells of Kang et al. with the remainder of the isolated stromal vascular fraction. One would be motivated to make this modification because Dykstra et al. teach that the differentiated cells of the stromal vascular fraction may have additional therapeutic benefits (See fig. 1). There would be a reasonable expectation of success in doing so because the stromal vascular fraction could readily be administered via Ommaya reservoir.
Further, it would have been obvious to one having ordinary skill in the art that the expression of heterologous BDNF in adipose-derived stromal cells in the modified method of Kang et al. may increase Wnt signaling within the cells, thereby reading on “wnt-activated”. The data of B. Chen et al. demonstrate the BDNF increases Wnt signaling in one type of stem cell (neural stem cells), and one of ordinary skill in the art could reasonably infer that similar results could be obtained in other types of stem cells.
Regarding claim 29: Following the discussion of claims 24, 27-28, 30, 36, and 40, Kang et al. do not expressly teach the stem cells as comprising exosomes.
K. Chen et al. (2016) teach that adipose-derived stem cells secrete exosomes (which reads on “comprise exosomes”, which can be used for preserving neurological function (See Abstract and page 74552, col. 1, ¶2-3).
Regarding claim 31: Following the discussion of claims 24, 27-28, 30, 36, and 40, Kang et al. teach the expression of BDNF in modified cells but do not expressly teach BDNF as an anti-inflammatory pharmaceutical. However, Jiang et al. teach that BDNF decreases local inflammation in a rat model of ischemic stroke by increasing expression of anti-inflammatory cytokines and inhibiting expression of pro-inflammatory cytokines (See section 3.4-3.5).
Regarding claim 38: Following the discussion of claims 24, 27-28, 30, 36, and 40, Kang et al. teach the administration of adipose-derived stem cells modified to express β-galactosidase and do not expressly teach the use of cells that are not genetically modified. However, the experiments of Kang et al. examined functional outcomes on injured rats as well as the fates and phenotypes of the transplanted cells (See page 361, col. 2, full ¶1 and fig. 4-5), and one of ordinary skill in the art would recognize that unmodified adipose-derived stem cells could be readily substituted if only the functional effects of the cells were to be assessed.
Claims 24, 27-32, 36, 38, and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Kang et al. (Experimental Neurology, 2003), evidenced by K. Chen et al. (Oncotarget, 2016) and Jiang et al. (Mediators of Inflammation, 2010), in view of Fauzi et al. (Journal of Stem Cells & Regenerative Medicine, 2016), of record, Dykstra et al. (Stem Cells Translational Medicine, 2017), and B. Chen et al. (Journal of Neuroscience Research, 2012), further in view of Kondo et al. (Nature, 2015).
The teachings of Kang et al., K. Chen et al., Jiang et al., Fauzi et al., Dykstra et al., and B. Chen et al. are set forth in the rejection above and are incorporated herein in their entirety.
Regarding claim 32: Following the discussion of claims 24, 27-28, 30, 36, and 40, Kang et al., evidenced by K. Chen et al. and Jiang et al., modified by Fauzi et al., Dykstra et al., and B. Chen et al., render obvious the injection of a modified stromal vascular fraction by Ommaya reservoir but do not teach the inclusion of an antibody.
Kondo et al. teach the intraventricular administration of an antibody against cis P-tau in mice for preventing neurodegeneration (See Abstract and Methods).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method rendered obvious by Kang et al., evidenced by K. Chen et al. and Jiang et al., modified by Fauzi et al., Dykstra et al., and B. Chen et al., to comprise an anti-cis P-tau antibody, such as is taught by Kondo et al., in the stem cell suspension. One would be motivated to make this modification because Kondo et al. teach that the antibody blocks cis P-tau, which is associated with neurodegenerative disorders such as Alzheimer’s disease (See Abstract). There would be a reasonable expectation of success in making this modification because an anti-cis P-tau antibody could be readily included in a composition for intraventricular injection via Ommaya reservoir.
Claims 24, 27-28, 30-31, 33-34, 36, 38, and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Kang et al. (Experimental Neurology, 2003), evidenced by K. Chen et al. (Oncotarget, 2016) and Jiang et al. (Mediators of Inflammation, 2010), in view of Fauzi et al. (Journal of Stem Cells & Regenerative Medicine, 2016), of record, Dykstra et al. (Stem Cells Translational Medicine, 2017), and B. Chen et al. (Journal of Neuroscience Research, 2012), further in view of Palejwala et al. (Surgical Neurology International, 2014).
The teachings of Kang et al., K. Chen et al., Jiang et al., Fauzi et al., Dykstra et al., and B. Chen et al. are set forth in the rejections above and are incorporated herein in their entirety.
Regarding claims 33-34: Following the discussion of claims 24, 27-28, 30, 36, and 40, Kang et al., evidenced by K. Chen et al., Jiang et al., modified by Fauzi et al., Dykstra et al., and B. Chen et al., render obvious the injection of a modified stromal vascular fraction by Ommaya reservoir but do not teach the use of a ventriculoperitoneal shunt.
Palejwala et al. teach the use of an Ommaya reservoir together with a ventriculoperitoneal shunt for maximizing delivery of intraventricular chemotherapy in a patient with hydrocephalus (See Abstract). The shunt comprised a high-resistance programmable valve (See Abstract).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method rendered obvious by Kang et al., evidenced by K. Chen et al. and Jiang et al., modified by Fauzi et al., Dykstra et al., and B. Chen et al., to comprise the use of a programmable shunt, such as is taught by Palejwala et al. One would be motivated to make this modification because Palejwala et al. teach that the shunt maximizes intraventricular dissemination of therapeutic agents in patients with hydrocephalus, and Palejwala et al. demonstrate that it can be used successfully with an Ommaya reservoir (See Abstract).
Claims 24, 27-31, 36, 38, and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Kang et al. (Experimental Neurology, 2003), evidenced by K. Chen et al. (Oncotarget, 2016) and Jiang et al. (Mediators of Inflammation, 2010), in view of Fauzi et al. (Journal of Stem Cells & Regenerative Medicine, 2016), of record, Dykstra et al. (Stem Cells Translational Medicine, 2017), and B. Chen et al. (Journal of Neuroscience Research, 2012), further in view of Williams et al. (US 20120201890 A1).
The teachings of Kang et al., K. Chen et al., Jiang et al., Fauzi et al., Dykstra et al., and B. Chen et al. are set forth in the rejections above and are incorporated herein in their entirety.
Regarding claim 37: Following the discussion of claims 24, 27-28, 30, 36, and 40, Kang et al., evidenced by K. Chen et al., Jiang et al., modified by Fauzi et al., Dykstra et al., and B. Chen et al., render obvious the injection of a modified stromal vascular fraction by Ommaya reservoir but do not teach the stromal vascular fraction as allogeneic.
Williams et al. teach the use of the stromal vascular fraction in transplantation for treating a disease or disorder (See Abstract and ¶0119). The stromal vascular fraction can be introduced into individuals as either autologous or allogeneic transplants (See ¶0155).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method rendered obvious by Kang et al., evidenced by K. Chen et al., Jiang et al., modified by Fauzi et al., Dykstra et al., and B. Chen et al., to comprise an allogeneic stromal vascular fraction. One would have been motivated to make this modification because Williams et al. suggest that autologous and allogeneic stromal vascular fractions can be used interchangeably (See ¶0155), and such a modification could be readily performed.
Allowable Subject Matter
Claims 35, 39, and 41 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter:
The prior art does not teach or suggest a system comprising a ventricle-coupled reservoir containing a therapeutic suspension comprising a stromal vascular fraction concentrate, wherein the suspension comprises endorphins, wherein the stromal vascular fraction comprises 7-8% ADSCs and 7-8% blood cell progenitors, or wherein the ADSCs comprise Wnt-activated MSCs and more than 50% of the Wnt-activated MSCs exhibit elevated expression of Lgr5 and/or Nestin.
Conclusion
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/J.S.S./Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633