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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.
Remarks
The amendments and remarks filed on 01/20/2026 have been entered and considered. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action. The rejections and/or objections presented herein are the only rejections and/or objections currently outstanding. Any previously presented objections or rejections that are not presented in this Office Action are withdrawn.
Claims 1-3, 5-13 and 16-28 are pending.
Claims 4 and 14-15 are cancelled.
Claims 27-28 are new.
Claims 2-3, 6-8, 17, and 24-26 are withdrawn.
Claims 1, 5, 9-13, 16, 18-23, and 27-28 have been examined on the merits.
Priority
This application, U.S. Application number 17/309178, is a national stage entry of International Application Number PCT/US2019/059683, filed on 11/04/2019, which claims the priority to U.S. provisional application number 62/755,553 filed on 11/04/2018.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 1/20/2026 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97., and has been considered by the examiner.
Rejections - Withdrawn
The rejections of Claims 1, 5, 9-13, 16, and/or 18-23 under 35 U.S.C. 103 over Chen et al. in view of Wang et al., Ichim et al., Huang et al., Denu et al., Lim et al. and/or Sun et al. are withdrawn in favor of the rejections listed below.
The provisional rejections of Claims 1, 5, 9-13, 16, and/or 18-23 on the ground of nonstatutory obviousness-type double patenting over claims of U.S. Application No. 17/755837 in view of Chen et al., Wang et al., Ichim et al., Huang et al., Denu et al., Lim et al. and/or Sun et al. are withdrawn in favor of the rejections listed below.
The provisional rejections of Claims 1, 5, 9-13, 16, and/or 18-23 on the ground of nonstatutory obviousness-type double patenting over claims of U.S. Application No. 17/999588 in view of Chen et al., Wang et al., Ichim et al., Huang et al., Denu et al., Lim et al. and/or Sun et al. are withdrawn in favor of the rejections listed below.
8. The provisional rejections of Claims 1, 5, 9-13, 16, and/or 18-23 on the ground of nonstatutory obviousness-type double patenting over claims of U.S. Application No. 18/057262 in view of Chen et al., Wang et al., Ichim et al., Huang et al., Denu et al., Lim et al. and/or Sun et al. are withdrawn in favor of the rejections listed below.
Claim Interpretation
Claim 28 is directed to a method of inducing regeneration and/or healing in the brain of an individual suffered from a stroke and/or transient ischemic attack, comprising steps: enriching a population of fibroblasts enriched for fibroblasts expressing CXCR4 and CD73; and administering enriched fibroblasts to the individual. The claim does not specifically recite any limitation to define how the enriching step is conducted. Based on the disclosure of the specification and Applicant’s declaration under 37 CFR 1.132 filed on 1/20/2026, the enriching step in the claim is interpreted as: enriching a unsorted population of fibroblasts for fibroblasts expressing CD73 and CXCR4 by isolating or purifying the fibroblasts expressing CD73 and CXCR4 from the unsorted population of fibroblasts, thereby generating a population of enriched fibroblasts for expressing CD73 and CXCR4”.
Claim Rejections - 35 USC § 112, Second Paragraph
Claim 27 is 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 pre-AIA the applicant regards as the invention.
Claim 27 is indefinite due to the recitation of “wherein the population of fibroblasts … enriched for fibroblasts expressing CXCR4 and CD73”. It is noted that the term ‘enriched” is a relative term and it is not defined in the specification. Given the claim does not recite any comparison phase, it is unclear based on which specific benchmark the recited population of fibroblasts can be considered to be enriched for CXCR4+ and CD73+ fibroblasts. For the purpose of examination, the phrase is interpreted as “wherein the population of fibroblasts are enriched for fibroblasts expressing CXCR4 and CD73 by isolating or purifying the fibroblasts expressing CXCR4 and CD73 from an unsorted population of fibroblasts”, based on the disclosure of the specification and Applicant’s declaration under 37 CFR 1.132 filed on 1/20/2026.
Claim Rejections - 35 USC § 103
Claims 1, 5, 9-13, 16, 18, and 20-23 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (J. Neuropathol. Exp. Neurol., 2012, 71(12): 1123-1136, of record) in view of Wang et al. (Current Drug Targets, 2012, 13:166-172, of record) and Ichim et al. (US 2018/0071342, published on 3/15/2018, cited in IDS), as evidenced by Denu et al. (Acta Haematologica, 2016, 136: 85-97, cited in IDS).
Chen et al. teach that intracerebral hemorrhage (ICH) is a devastating form of stroke (i.e. a hemorrhagic stroke) (page 1123, right col., Introduction/lines 1-2). Chen et al. further teach a rodent model of a hemorrhagic stroke, and a method of inducing regeneration or healing response in the brain of an individual (mouse) that has suffered from intracerebral hemorrhage (hemorrhagic stroke), comprising: administering locally to the brain of the individual a therapeutically effective amount of un-transfected fibroblasts (3T3 cell lines) or BDNF-transfected fibroblasts that overexpress a brain-derived neurotrophic factor (BDNF), wherein administration of fibroblasts leads regeneration of the brain, which results in less brain tissue loss and more surviving neurons compared to control, and induce/enhance functional restoration of mice (title, abstract; page 1124/left col./paras 3-4, and right col/last para; page 1125/left col./paras 1-2, Figs. 1-2).
Regarding the limitation “CXCR-4” recited in the amended claim 1, Chen et al. are silent about whether fibroblasts express CXCR-4. However, it would have been obvious to administer to the individual transfected fibroblasts that express CXCR-4 (in addition to BDNF) in the method of Chen et al. for inducing regeneration or healing response in the brain suffered from stroke, because CXCR-4 plays an important role in facilitating neurological recovery in an individual subsequent to a stroke, and it is known in the art to transfect cells with BDNF and CXCR4 for the cells to possess enhanced neuromodulatory and neuroprotective properties for treating stroke. In support, Ichim et al. teach inducing and accelerating neurological recovery subsequent to a stroke by administering cells derived from amniotic fluid into a patient having undergone stroke (abstract), wherein the amniotic fluid cells are transfected with heterologous genes, such as gene of BDNF and gene of CXCR4, for the cells to possess enhanced neuromodulatory and neuroprotective properties (para 0098, lines 1-8, 12-13, and 23). Further in support, Wang et al. teach that CXCR-4 (a G-protein coupled receptor) works in junction with a chemokine ligand CXCL12 that is expressed by all cell types in the central nervous system, and plays important roles in repairing after a stroke, which include inflammatory response, focal angiogenesis, and recruiting BMCs and neural progenitor cells to injury regions (abstract/lines 1-8).
Regarding the limitations about phenotypes of fibroblasts: CD73+, CD105+, CD90+, and CD45-, respectively recited in the claims 1, 13, 16, and 18, Chen et al. teach the fibroblasts used in their method are fibroblasts of Swiss albino mouse 3T3 cell lines (page 1124, left col, para 3/line 1) and they are silent about whether the fibroblasts have the phenotypes of CD73+, CD105+, and/or CD90+ (i.e. expressing CD73, CD105, and/or CD90). However, it appears to be a common feature for fibroblast cell lines to have the phenotypes of CD73+, CD105+, CD90+, and CD45-, as evidenced by Denu et al., who investigated phenotypic characteristics of four different fibroblast cell lines well-established in the art, which are derived from various human tissues including foreskin, lung, and breast (abstract/the section of “Methods”, page 86/right col./para 3); and demonstrated that fibroblasts of all the four cell lines they tested express the surface markers CD73, CD105, and CD90, but do not express CD45 (just like mesenchymal stromal/stem cells or MSCs), i.e. being positive for CD73, CD90, and CD105, and negative for CD45 (page 87/right col./last paragraph/lines 1-4 and 7-11, Fig. 2).
As such, it is highly likely that the fibroblasts of Swiss albino mouse 3T3 cell lines are positive for CD73 along with CD90 and CD105, and are negative for CD45. “As a practical matter, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons therewith.” In re Brown, 459 F.2d 531, 535, 173 USPQ 685, 688 (CCPA 1972). The Patent and Trademark Office is not equipped to conduct experimentation in order to determine whether Applicants’ fibroblasts differ in the claimed phenotypes and, if so, to what extent, from that of discussed references. Therefore, with the showing of the references, the burden is shifted to Applicant to show a novel or unobvious difference between the claimed fibroblasts and the fibroblasts of the prior art, in the phenotypes of CD73+, CD105+, CD90+, and CD45-.
Regarding Claims 9-11, Chen et al. teach the fibroblasts possess regenerative activity and produce BDNF, as indicated above. With regard to the limitation in claim 11, Chen et al. further teach that BDNF augments neurogenesis of the brain and induces neuronal differentiation of endogenous progenitor cells (stem cells) (page 1123, right col., las full para/lines 3-7), which suggests BDNF stimulates differentiation and proliferation of neural and stem cells. Furthermore, the limitation in claim 11 is directed to inherent features/properties of the fibroblasts. The fibroblasts in the method of the Chen et al. have all the structural limitations of fibroblasts recited in the claim. In the absence of contrary, it is presumed that substances/cells having substantially the same structures have the same properties.
Regarding Claim 12, this claim does not require the claimed method to comprise an active step of separating fibroblasts from the tissues recited in the claim. Chen et al. are silent about which tissue the fibroblasts are derived/separated from. However, the limitation recited in the claim is a product-by-process limitation, because it describes fibroblasts and a process/steps involved in producing the fibroblasts from the tissues.
Product-by-process limitations are not limited to the manipulations of the recited steps, only to the structure implied by the steps. Thus, determination of patentability is based on the product itself, not on a method for its production. The fibroblasts taught by Chen et al. appears to be structurally the same as the fibroblasts recited in the claim, or be an obvious varied since the prior art teaches a substantially similar product. Now, the burden is shifted to applicant to show a novel or unobvious difference. See MPEP 2113.
Regarding Claim 18, Chen et al. teach culturing (i.e. expanding) fibroblasts and also isolating trypsinized fibroblasts and further isolating transfected fibroblasts after culturing, prior to the administration step (page 1124, left col., paras 3-4). It is a common practice in the art to isolate cells and further expand the cells in a culture medium. The teachings of Chen et al. would render the claim 18 to be obvious.
Regarding Claims 21-23, Chen et al. are silent about applying an additional therapy or a medical procedure for a brain injury of the individual. However, it would have been obvious to one of ordinary skill in the art to further provide a medical procedure (additional therapy) of repairing skull fractures to the individual in the method of Chen et al. for maintaining the individual under a stable and healthy condition, thus allowing the effect of fibroblasts to be revealed in a long term. This is because Chen et al. teach that the skull of the individual is damaged and has fractures due to administration of fibroblasts or agent into the brain through a burr hole of the skull, which is generated by breaking the skull of the individual (page 1125, left col., para 2, lines 7 and 12-14). One of ordinary skill of the art would have been recognized that it is necessary to repair the skull for maintaining the individual under good and stable condition.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (J. Neuropathol. Exp. Neurol., 2012, 71(12): 1123-1136, of record) in view of Wang et al. (Current Drug Targets, 2012, 13:166-172, of record), Ichim et al. (US 2018/0071342, published on 3/15/2018, cited in IDS), as applied to Claims 1, 5, 9-13, 16, 18, and 20-23, further in view of Lim et al. (Stem Cell Research & Therapy, 2011, 2:38, pages 1-13, of record), as evidenced by Denu et al. (Acta Haematologica, 2016, 136: 85-97, cited in IDS).
The teachings of Chen et al. as modified by Wang and Ichim are described above.
Regarding Claim 19, Chen et al. teach directly administering fibroblasts through the skull into the brain (i.e. intracerebral delivery), and they do not teach administering the fibroblasts intrathecally.
Lim et al. teach a cell-based therapy for treating cerebral ischemia (ischemic stroke) in a rat stroke model by intrathecally delivering mesenchymal stem cells (MSCs) into the cerebrospinal fluid (CSF) through the spinal cord, and demonstrate that a significantly higher number of migrated cells migrated into the ischemic area, and the cells survived and significantly improved motor function, reduced ischemic damage, and differentiated significantly into neurons and astrocytes (title, abstract, page 3/left col/para 2). Lim et al. further teach that intrathecal delivery is considered as a safe, effective approach for cell transplantation and recovery of ischemic damage, and is useful and feasible for treating brain injuries (page 2: the para spanning both columns; page 11: left col/the section of conclusions).
It would have been obvious to one of ordinary skill in the art to modify the method suggested by Chen et al. and other cited prior art by administering the fibroblasts to the individual intrathecally for inducing regeneration or healing response in the brain, because intrathecal administration is a route commonly used in the art for delivering a therapeutic agent into the CSF and brain, and it is well known in the art that cells delivered through intrathecal route achieve brain-specific sites and is effective at treating neurological diseases including stroke, as supported by Lim et al. Furthermore, delivering fibroblasts through intrathecal route is an alternative approach of the intracerebral delivery taught by Chen et al., for directly delivery fibroblasts into the CSF and brain. Lim et al. teach that the intrathecal delivery has the advantage of being safe for cell transplantation, effective for recovery of brain, and useful and feasible for treating brain injuries. Although cells taught by Lim et al. are not fibroblasts, it would have been obvious to try administering fibroblasts to the individual in the method suggested by Chen et al. for inducing regeneration and healing response in the damaged brain, because there are a limited number of routes known in the art for directly delivering cells into the CSF and brain of an animal for cell-based therapy of a stroke. See MPEP 2143 I.E., the rationale “obvious to try” supports a conclusion of obviousness when there is a finite number of identified and predictable solutions in the prior art, and choosing from such a finite number of identified and predictable solutions would have a reasonable expectation of success.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Claims 1, 5, 9-13, 16, 18, and 20-23 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (J. Neuropathol. Exp. Neurol., 2012, 71(12): 1123-1136, of record) in view of Wang et al. (Current Drug Targets, 2012, 13:166-172, of record), Ichim et al. (US 2018/0071342, published on 3/15/2018, cited in IDS), and Denu et al. (Acta Haematologica, 2016, 136: 85-97, cited in IDS).
This rejection renders the phenotypic limitations in the claims 1, 13, 16, and 18 to be obvious based on a rational different from that in the 103 rejection above (pages 7-8).
Chen et al. teach that intracerebral hemorrhage (ICH) is a devastating form of stroke (i.e. a hemorrhagic stroke) (page 1123, right col., Introduction/lines 1-2). Chen et al. further teach a rodent model of a hemorrhagic stroke, and a method of inducing regeneration or healing response in the brain of an individual (mouse) that has suffered from intracerebral hemorrhage (hemorrhagic stroke), comprising: administering locally to the brain of the individual a therapeutically effective amount of un-transfected fibroblasts (3T3 cell lines) or BDNF-transfected fibroblasts that overexpress a brain-derived neurotrophic factor (BDNF), wherein administration of fibroblasts leads regeneration of the brain, which results in less brain tissue loss and more surviving neurons compared to control, and induce/enhance functional restoration of mice (title, abstract; page 1124/left col./paras 3-4, and right col/last para; page 1125/left col./paras 1-2, Figs. 1-2).
Regarding the limitation “CXCR-4” recited in the amended claim 1, Chen et al. are silent about whether fibroblasts express CXCR-4. However, it would have been obvious to administer to the individual transfected fibroblasts that express CXCR-4 (in addition to BDNF) in the method of Chen et al. for inducing regeneration or healing response in the brain suffered from stroke, because CXCR-4 plays an important role in facilitating neurological recovery in an individual subsequent to a stroke, and it is known in the art to transfect cells with BDNF and CXCR4 for the cells to possess enhanced neuromodulatory and neuroprotective properties for treating stroke. In support, Ichim et al. teach inducing and accelerating neurological recovery subsequent to a stroke by administering cells derived from amniotic fluid into a patient having undergone stroke (abstract), wherein the amniotic fluid cells are transfected with heterologous genes, such as gene of BDNF and gene of CXCR4, for the cells to possess enhanced neuromodulatory and neuroprotective properties (para 0098, lines 1-8, 12-13, and 23). Further in support, Wang et al. teach that CXCR-4 (a G-protein coupled receptor) works in junction with a chemokine ligand CXCL12 that is expressed by all cell types in the central nervous system, and plays important roles in repairing after a stroke, which include inflammatory response, focal angiogenesis, and recruiting BMCs and neural progenitor cells to injury regions (abstract/lines 1-8).
Regarding the limitations about phenotypes of fibroblasts CD73+, CD105+, CD90+, and/or CD45- respectively recited in the claims 1, 13, 16, and 18, Chen et al. are silent about specific phenotypes of CD73, CD105, CD90, and CD45 of fibroblasts. However, it would have been obvious to use fibroblasts with CD73+, CD105+, CD90+, and/or CD45-, transfect with CXCR-4 and BDNF, and then administer the fibroblasts to the individual in the method suggested by Chen et al., Ichim et al. and Wang et al. for inducing regeneration or healing response in the brain suffered from stroke. This is because fibroblasts with phenotypes of CD73+, CD105+, CD90+ and CD45- are well established and readily available in the art; and these fibroblasts have the advantages of easy access and propagation and they are commonly used as paradigms of fibroblasts. In support, Denu et al. teach multiple types of fibroblasts derived from various human tissues (foreskin, lung, breast) and investigated their cell surface markers, and demonstrated that all these fibroblasts express the surface markers of mesenchymal stromal/stem cells (MSCs), i.e. being positive for CD73, CD90, and CD105, and negative for CD45 (abstract, page 86/right col/para 3, page 87/last paragraph under Results/lines 1-4 and 7-11, Fig. 2). Denu et al. teach these fibroblasts are well-established and have been used as paradigms of fibroblasts for a decade or more and can be easily cultured/propagated in conventional DMEM culture media (page 86: left col/last 6 lines, right col/para 3).
Regarding Claim 12, Chen et al. do not teach that the fibroblasts are derived from skin or foreskin. However, it would have been obvious to apply fibroblasts derived from skin/foreskin with phenotypes of CD73+, CD105+, and CD90+ in the method suggested by Chen et al. and other cited prior art for treating the individual with a stroke, because the skin is an easy and common source for obtaining fibroblasts having phenotypes of CD73+, CD105+, and CD90+, as supported by Denu et al.
Regarding Claim 18, Chen et al. teach isolating and expanding fibroblasts prior to the administration step. It would have been obvious to isolate and expand fibroblasts that do not express CD45 prior to the administration in the method suggested by Chen et al. and other cited prior art for treating the individual with a stroke, because it is well known in the art that fibroblasts with CD73+, CD105+, and CD90+ phenotypes do not express CD45, as supported by Denu et al.
Regarding Claims 9-11 and 21-23, these claims would have been obvious over the teachings of Chen et al. for the reasons indicated above (see pages 8-9).
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (J. Neuropathol. Exp. Neurol., 2012, 71(12): 1123-1136, of record) in view of Wang et al. (Current Drug Targets, 2012, 13:166-172, of record), Ichim et al. (US 2018/0071342, published on 3/15/2018, cited in IDS), and Denu et al. (Acta Haematologica, 2016, 136: 85-97, cited in IDS), as applied to Claims 1, 5, 9-13, 16, 18, and 20-23, further in view of Lim et al. (Stem Cell Research & Therapy, 2011, 2:38, pages 1-13, of record).
The teachings of Chen et al. as modified by Wang, Ichim, Huang, and Denu are described above.
Regarding Claim 19, Chen et al. teach directly administering fibroblasts through the skull into the brain (i.e. intracerebral delivery), and they do not teach administering the fibroblasts intrathecally.
The teachings of Lim et al. are described above.
It would have been obvious to one of ordinary skill in the art to modify the method suggested by Chen et al. and other cited prior art by administering the fibroblasts to the individual intrathecally for inducing regeneration or healing response in the brain, because intrathecal administration is a route commonly used in the art for delivering a therapeutic agent into the CSF and brain, and it is well known in the art that cells delivered through intrathecal route achieve brain-specific sites and is effective at treating neurological diseases including stroke, as supported by Lim et al. Furthermore, delivering fibroblasts through intrathecal route is an alternative approach of the intracerebral delivery taught by Chen et al., for directly delivery fibroblasts into the CSF and brain. Furthermore, Lim et al. teach that the intrathecal delivery has the advantage of being safe for cell transplantation, effective for recovery of brain, and useful and feasible for treating brain injuries. Although cells taught by Lim et al. are not fibroblasts, it would have been obvious to try administering fibroblasts to the individual in the method suggested by Chen et al. for inducing regeneration and healing response in the damaged brain, because there are a limited number of routes known in the art for directly delivering cells into the CSF and brain of an animal for cell-based therapy. See MPEP 2143 I.E., the rationale “obvious to try” supports a conclusion of obviousness when there is a finite number of identified and predictable solutions in the prior art, and choosing from such a finite number of identified and predictable solutions would have a reasonable expectation of success.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Double Patenting
Claims 1, 5, 9-13, 16, and 18-22 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1, 3, 5, 11, 13-14, 20-26, 28-35, 37, 42-43, 49-52, 58-59, and 76-82 of copending Application No. 17/755837 in view of Wang et al. (Current Drug Targets, 2012, 13:166-172, of record), Ichim et al. (US 2018/0071342, published on 3/15/2018, cited in IDS), and Denu et al. (Acta Haematologica, 2016, 136: 85-97, cited in IDS).
The claims of the copending ‘837 application are directed in part to a method of
treating a ischemic stroke or hemorrhagic stroke in a subject, comprising a step of providing to the subject an effective amount of fibroblasts intraventricularly, intrathecally, or intravenously; wherein the fibroblasts stimulate proliferation of neural progenitor cells in the subject; wherein the fibroblasts reduce neuroinflammation and provide neuroprotection in the subject; wherein the fibroblasts possess ability to produce or stimulate the production of VEGF, NGF, BDNF, PDGF and/or PDGF-B; wherein the method further comprises providing to the subject a treatment with TNF-a inhibitor or anti-apoptotic agent (reading on generic term “additional therapy” recited in the instant claims 21 and 22).
Regarding the limitation “CXCR-4” recited in the instant claim 1, the claims of the ‘837 application do not describe that fibroblasts express CXCR-4.
The teachings of Wang, Ichim, and Denu are described above.
It would have been obvious to administer to the individual transfected fibroblasts that express CXCR-4 (along with BDNF) in the method of the ‘837 application for inducing regeneration or healing response in the brain and treating stroke, because CXCR-4 plays an important role in facilitating neurological recovery in an individual subsequent to a stroke, and it is known in the art to transfect cells with BDNF and CXCR4 for the cells to possess enhanced neuromodulatory and neuroprotective properties for treating stroke, as supported by Ichim et al. and Wang et al.
Regarding the limitation about CD73, CD105, CD90, and CD45 respectively recited in the claims 1, 13, 16 and 18, the claims of the ‘837 application do not describe that the fibroblasts has the CD73+, CD105+, and CD90+ phenotypes. However, it would have been obvious to administer to the individual fibroblasts expressing CD73, CD90, and CD105 (expressing CXCR-4 and BDNF), but not CD45 in the method suggested by the claims of the ‘837 application, Ichim et al. and Wang et al., for treating the individual suffering from stroke, because fibroblasts with phenotypes of CD73+, CD105+, CD90+ and CD45- are well-established and commonly used in the art, as supported by Denu et al. et al.
Regarding the instant claim 12, the claims of the ‘837 applications do not teach that the fibroblasts are derived from skin. However, it would have been obvious to administer the fibroblasts derived from skin to the individual in the methods of the ‘837 application for treating the individual suffering from a stroke, because skin is an easy and common source for obtaining fibroblasts expressing CD73, CD90, and CD105, as supported by Denu et al.
Regarding Claim 18, it would have been obvious to isolate and expand fibroblasts that do not express CD45 prior to the administration in the method suggested by the claims of the ‘837 applications for treating the individual with a stroke, because it is well known in the art that fibroblasts with CD73+, CD105+, and CD90+ phenotypes do not express CD45, as supported by Denu et al. Furthermore, it is a common practice in the art to isolate and culture (expand) fibroblasts in a culture medium for obtaining a desired amount of cells, as supported by Denu et al.
Therefore, in view of the cited prior art, the method of Claims 1, 5, 9-13, 16, and 18-22 of the instant application is deemed obvious over claims 1, 3, 5, 11, 13-14, 20-26, 28-35, 37, 42-43, 49-52, 58-59, and 76-82 of copending Application No. 17/755837.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Claims 1, 9-13, 16, 18, and 21-22 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-3, 8-10, 29, and 39 of copending Application No. 17/999588 in view of Wang et al. (Current Drug Targets, 2012, 13:166-172, of record), Ichim et al. (US 2018/0071342, published on 3/15/2018, cited in IDS), and Denu et al. (Acta Haematologica, 2016, 136: 85-97, cited in IDS).
The claims of the copending ‘588 application are directed in part to a method of
Increasing efficacy of a fibroblast-based treatment, comprising: the steps: a) treating dysbiosis in an individual in need thereof; and b) administering the fibroblast-based treatment to the individual, wherein the fibroblast-based treatment is a fibroblast-based cellular treatment, and is for treating a stroke; wherein the fibroblast-based cellular treatment comprises fibroblast cells, which possess regenerative activity; wherein the regenerative activity of the fibroblasts cells includes augmentation of tissue self-renewal; and wherein the fibroblasts cells express CD105 and CD73. It is noted that the treatment of dysbiosis in the individual in the claimed method of the ‘588 application reading on generic term “additional therapy” recited in the instant claims 21 and 22.
Regarding the limitation “CXCR-4” recited in the instant claim 1, the claims of the ‘588 application do not describe that fibroblasts express CXCR-4.
The teachings of Wang, Ichim, and Denu are described above.
It would have been obvious to administer to the individual transfected fibroblasts that express CXCR-4 in the method of the ‘588 application for inducing regeneration or healing response in the brain and treating stroke, because CXCR-4 plays an important role in facilitating neurological recovery in an individual subsequent to a stroke, and it is known in the art to transfect cells with CXCR4 for the cells to possess enhanced neuromodulatory and neuroprotective properties for treating stroke, as supported by Ichim et al. and Wang et al.
Regarding the limitation about CD73, CD105, CD90, and CD45 respectively recited in the claims 1, 13, 16 and 18, the claims of the ‘588 application teach the fibroblasts cells express CD105 and CD73. It would have been obvious to administer to the individual fibroblasts further expressing CD90 (expressing CXCR-4), but not CD45 in the method suggested by the claims of the ‘588 application, Ichim et al. and Wang et al., for treating the individual suffering from stroke, because fibroblasts with phenotypes of CD73+, CD105+, CD90+ and CD45- are well-established and commonly used in the art, as supported by Denu et al. et al.
Regarding Claims 10-11, the claims of the copending ‘588 application teach the fibroblasts possess regenerative activity. Although they are silent about the specific regenerative activity recited in claims 10-11, the further limitations in these claims are directed to inherent features/properties of the fibroblasts. The fibroblasts in the method suggested by the ‘588 application have all the structural limitations of fibroblasts recited in the instant claim 1. In the absence of contrary, it is presumed that substances/cells having substantially the same structures have the same properties. Therefore, the fibroblasts of the copending ‘588 application meet the limitations recited in Claims 10-11.
Regarding the instant claim 12, the claims of the ‘588 applications do not teach that the fibroblasts are derived from skin. However, it would have been obvious to administer the fibroblasts derived from skin to the individual in the method of the ‘588 application for treating the individual suffering from a stroke, because skin is an easy and common source for obtaining fibroblasts expressing CD73, CD90, and CD105, as supported by Denu et al.
Regarding Claim 18, it would have been obvious to isolate and expand fibroblasts that do not express CD45 prior to the administration in the method suggested by the claims of the ‘588 applications for treating the individual with a stroke, because it is well known in the art that fibroblasts with CD73+, CD105+, and CD90+ phenotypes do not express CD45, as supported by Denu et al. Furthermore, it is a common practice in the art to isolate and culture (expand) fibroblasts in a culture medium for obtaining a desired amount of cells, as supported by Denu et al.
Therefore, in view of the cited prior art, the method of Claims 1, 9-13, 16, 18, and 21-22 of the instant application is deemed obvious over claims 1-3, 8-10, 29, and 39 of copending Application No. 17/999588.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Claims 1, 5, 9-13, 16, and 18 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-17, 19-21, and 23-24 of copending Application No. 18/057262 in view of Wang et al. (Current Drug Targets, 2012, 13:166-172, of record), Ichim et al. (US 2018/0071342, published on 3/15/2018, cited in IDS), and Denu et al. (Acta Haematologica, 2016, 136: 85-97, cited in IDS).
The claims of the copending ‘262 application are directed in part to a method of
treating a disease and/or condition in an individual, comprising: administering a therapeutically effective amount of fibroblasts and/or fibroblast-like cells to the individual, fibroblasts being contacted with one or more hormones; wherein the disease can be stroke and/or ischemia; wherein the fibroblasts can be derived from skin tissue; wherein the fibroblast population comprises fibroblasts that are plastic adherent; and wherein the fibroblasts are obtained by a purification method for the marker CD105.
The teachings of Wang, Ichim, and Denu are described above.
Regarding the limitation “CXCR-4” recited in the instant claim 1, the claims of the ‘262 application do not describe that fibroblasts express CXCR-4. However, it would have been obvious to administer to the individual transfected fibroblasts that express CXCR-4 in the method of the ‘262 application for inducing regeneration or healing response in the brain and treating stroke, because CXCR-4 plays an important role in facilitating neurological recovery in an individual subsequent to a stroke, and it is known in the art to transfect cells with CXCR4 for the cells to possess enhanced neuromodulatory and neuroprotective properties for treating stroke, as supported by Ichim et al. and Wang et al.
Regarding the limitation about CD73, CD105, CD90, and CD45 respectively recited in the claims 1, 13, 16 and 18, the claims of the ‘262 application teach the fibroblasts cells express CD105. It would have been obvious to administer to the individual fibroblasts further expressing CD73 and CD90 (expressing CXCR-4) in the method suggested by the claims of the ‘262 application, Ichim et al. and Wang et al., for treating the individual suffering from stroke, because fibroblasts with phenotypes of CD73+, CD105+, CD90+ and CD45- are well-established and widely used in the art, as supported by Denu et al. et al.
Regarding Claim 5, the claims of the copending ‘262 application teach the disease can be a combination of ischemia and stroke, i.e. ischemic stroke.
Regarding Claims 9-11, the further limitations in these claims are directed to inherent features/properties of the fibroblasts. The fibroblasts in the method of the copending ‘262 application have all the structural limitations of fibroblasts recited in the instant claim 1. In the absence of contrary, it is presumed that substances/cells having substantially the same structures have the same properties. Therefore, the fibroblasts of the copending ‘262 application the teachings of meet the limitations recited in Claims 9-11.
Regarding Claim 18, it would have been obvious to isolate and expand fibroblasts that do not express CD45 prior to the administration in the method suggested by the claims of the ‘262 applications for treating the individual with a stroke, because it is well known in the art that fibroblasts with CD73+, CD105+, and CD90+ phenotypes do not express CD45, as supported by Denu et al. Furthermore, it is a common practice in the art to isolate and culture (expand) fibroblasts in a culture medium for obtaining a desired amount of cells, as supported by Denu et al.
Therefore, in view of the cited prior art the method of Claims 1, 5, 9-13, 16, and 18 of the instant application is deemed obvious over claims 1-17, 19-21, and 23-24 of copending Application No. 18/057262.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Claims 20-23 and/or 5 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over the claims of copending Application Nos. 18/057262, 17/999588, and 17/755837, respectively, in view of Wang, Ichim, and Denu, as applied to Claims 1, 5, 9-13, 16, and/or 18-22, further in view of Chen et al. (J. Neuropathol. Exp. Neurol., 2012, 71(12): 1123-1136, of record).
The subject matter of the claims of the Application Nos. 18/057262, 17/999588, and 17/755837, as modified by Wang, Ichim, and Denu, are described above.
Regarding the instant claim 20, the claims of the ‘262 and ‘588 applications are silent about how fibroblasts are administered to the individual, and the claims of the ‘262, ‘837 and ‘588 applications do not teach administering cells locally to the brain.
The teachings of Chen et al. are described above.
It would have been obvious to administer the fibroblasts locally to the brain in the methods suggested by the ‘262, ‘837 and ‘588 applications and cited prior art, respectively, for treating the individual suffering from a stroke, because it is a common practice in the art to administer fibroblast cells locally into the brain for treating neurological diseases including a stroke, as supported by Chen et al.
Regarding Claims 21-23, the claims of the ‘262, ‘588, and ‘837 applications do not teach their claimed method comprises a step of providing a medical procedure of repairing skull fractures as an additional therapy. However, it would have been obvious to one of ordinary skill in the art to further provide a medical procedure (additional therapy) of repairing skull fractures to the individual in the method suggested by the claims of the copending applications for maintaining the individual under a stable and healthy condition. This is because Chen et al. teach that the skull of the individual is damaged and has fractures due to local administration of fibroblasts into the brain through a burr hole of the skull, which is generated by breaking the skull of the individual. One of ordinary skill of the art would have been recognized that it is necessary to repair the skull for maintaining the individual under good and stable condition.
Regarding the instant claim 5, the claims of the ‘588 application are silent about whether the stroke treated by their claimed method is a hemorrhagic stroke. However, it would have been obvious to practice the claimed method of the ‘588 application for treating a hemorrhagic stroke by administering fibroblasts to an individual suffered from hemorrhagic stroke, because it is well known in the art that fibroblasts are effective at treating hemorrhagic stroke, as supported by Chen et al.
Therefore, in view of the cited prior art, the method of Claims 20-23 and/or 5 of the instant application is deemed obvious over the claims of copending Application Nos. 18/057262, 17/999588, and 17/755837, respectively.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Claim 19 is provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over the claims of copending Application Nos. 18/057262 and 17/999588, respectively, in view of Wang, Ichim, and Denu, as applied to claims 1, 9-13, 16, 18, and/or 21-22, further in view of Lim et al. (Stem Cell Research & Therapy, 2011, 2:38, pages 1-13).
The subject matter of the claims of the Application Nos. 18/057262 and 17/999588 as modified by Wang, Ichim, and Denu are described above.
Regarding the instant claim 19, the claims of the ‘262 and ‘588 applications are silent about how fibroblasts are administered to the individual.
The teachings of Lim et al. are described above.
It would have been obvious to administer the fibroblasts to the individual intrathecally in the modified methods of the ‘262 and ‘588 applications, respectively, for treating the individual suffering from a stroke, because intrathecal administration is a route commonly used in the art for delivering a therapeutic agent, and it is well known in the art that cells delivered through intrathecal route achieve brain-specific sites and are effective at treating neurological diseases including a stroke, as supported by Lim et al.
Therefore, in view of the cited prior art, the method of Claim 19 of the instant application is deemed obvious over the claims of copending Application Nos. 18/057262 and 17/999588, respectively.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Claims 1, 5, 9-13, 18-23, and 27-28 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1, 3, 7-8, 16, 18, 27, 33, 38, 42, 52, 55, 64, 66, 68-69, and 71-73 of copending Application No. 17/996102 in view of Chen et al. (J. Neuropathol. Exp. Neurol., 2012, 71(12): 1123-1136, of record).
The claims of the copending ‘102 application are directed in part to a method of
stimulating regeneration of cells or tissue in an individual, comprising: administering an effective amount of fibroblasts to an anatomical area in need of cell or tissue regeneration in the individual, wherein the fibroblasts are administered locally or systemically; wherein the fibroblasts express CD73; wherein the fibroblasts express CXCR4; wherein the fibroblasts express CD105; and wherein the fibroblasts do not express CD45.
The claimed method of the ‘102 application differs from the instantly claimed method in that the claims of the ‘102 application do not specifically teach administering the fibroblasts to the brain for inducing regeneration of cells or tissue in the brain suffered from a stroke/hemorrhagic stroke.
The teachings of Chen et al. are described above.
It would have been obvious to administer fibroblasts that express CXCR-4 and CD73 (along with transfected BDNF) to the brain of the individual in the claimed method of the ‘102 application for inducing regeneration of cells or tissue in the brain and treating hemorrhagic stroke, because it is well known in the art that fibroblasts (transfected with BDNF) promote regeneration and functional recovery of the brain in an individual subsequent to hemorrhagic stroke, as supported by Chen et al.
Regarding the claims 27 and 28, it would have been obvious to include a step of enriching fibroblasts expressing CD73 and CXCR4 from an unsorted population of fibroblasts in the method suggested by the claims of the ‘102 application and Chen et al. for treating the stroke because the claims of the ‘102 application specifically require the fibroblasts to express CD73 and CXCR4 for inducing regeneration of cells or tissue.
Regarding the claims 9-12, 18, and 21-23, they would have been obvious over the combined teachings of the claims of the ‘102 application and Chen et. al. for the reasons indicated above.
Therefore, in view of the cited prior art, the method of Claims 1, 5, 9-13, 18-23, and 27-28 of the instant application is deemed obvious over the claims of copending Application No. 17/996102.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Allowable Subject Matter
The subject matter of Claims 27 and 28 is free of art.
Response to Arguments
Applicant's arguments about the rejection of claims 1, 9-13, 16, 18, and 21-23 in the response filed on 01/20/2026 (pages 6-11) have been fully considered but they are not persuasive for the following reasons.
In response to Applicant’s arguments based on inherency in the 01/20/2026 response (page 7), these arguments are misleading and unpersuasive because the 103 rejection of record is not based on the rational that fibroblasts used in the method of Chen inherently express CD73, CD90, and/or CD105. Rather, the obviousness is based on fibroblasts of CD73(+), CD90(+), CD105(+) and CD45(-) taught by the secondary references cited in the rejection. Applicant’s additional arguments in pages 7-8 of the response are based on the feature not recited in the claims, because none of the claims 1, 9-13, 16, 18, and 21-23 requires that all fibroblasts administered to an individual in the claimed method are positive for CD73, CD90, and CD105 and negative for CD45; furthermore, none of the claims require the fibroblasts to meet all these phenotypes at the same time. As evidenced by the Declaration under 37 CFR 1.132 by Dr. Ichim, an unsorted population of fibroblasts comprise both CD73(+) and CD73(-) fibroblasts and this unsorted population of fibroblasts also has the effect at increasing insulin after being transplanted. As such, even though the prior art cited in Applicant’s the arguments reveal that an unsorted population of fibroblasts comprise subpopulations of fibroblasts with CD73(-) or CD105(-) phenotype, the teachings of the cited prior art do not change the fact that the unsorted population of fibroblasts comprise subpopulations of fibroblasts with the phenotypes of CD73(+), CD90(+), CD105(+) and CD45(-). Thus, the unsorted population of fibroblasts used in the method suggested by Chen and other cited prior art meets the claimed limitations about CD73(+), CD90(+), CD105(+) and/or CD45(-). Finally, in response to Applicant’s arguments in page 8/last 2 lines, Examiner notes that the “at various stages” stated by Balducci can be considered as all stages, because Baldacci cannot reveal/find a single stage at which fibroblasts do not have the phenotypes of CD73(+), CD90(+), CD105(+) and CD45(-), and Baldacci has to use other surface markers in Table 30.1 for defining an MSC population. See Baldacci’s continuous teachings in page 442/right col/para 1/last 5 lines.
In response to Applicant’s arguments based different therapeutic effect between CD73(-) and CD73(+) fibroblasts showed in the Declaration under 37 CFR 1.132 by Dr. Ichim in the 01/20/2026 response (page 8/para 1), Examiner notes that the Declaration is insufficient to overcome the 103 rejection because the objective evidence of nonobviousness is not commensurate in scope with the claims. Specifically, the fibroblasts recited in the claim 1 is not limited to any enriched CD73(+) fibroblasts, which are sorted from an unsorted population of fibroblasts. Rather, the fibroblasts recited in the claim encompasses unsorted, non-selected, or unseparated populations of fibroblasts with any mixed subpopulations of phenotypic fibroblasts including those with CD73(-) phenotypes at any cell number.
In response to Applicant’s arguments based on the teachings of Huang et al. in the 01/20/2026 response (pages 9-10), it is noted that Huang et al. only compared FDSCs with a single fibroblast cell line. In view of the status of the prior art, it appears to be inconclusive whether these FDSCs are fibroblast cells, as evidenced by Hematti (Cytotherapy, 2012, 14: 516-521, cited in IDS), who teach that ex vivo culture-expanded MSC and fibroblasts are indistinguishable by morphology, cell-surface markers, differentiation potential and immunologic properties (see abstract/last 2 lines); and as evidenced by Wong et al. (British Journal of Dermatology, 2007 156:1149-1155, cited in IDS), who teach that Fibroblasts are mesenchymal cells that can be readily cultured in the laboratory (see Summary/first line); and as evidenced by Denu et al. (of record), who concluded that they could not find any immunophenotypic characteristic that distinguish fibroblasts from MSCs (see abstract/last 5 lines). Nevertheless, Huang et al. demonstrate that fibroblasts of the Hs68 cell line are positive for CD73, CD90, Oct-4, and Nanog, and negative for CD45 (Fig. 2, page 1494/left col/para 1/last 6 lines), all of which meet the fibroblast phenotypes recited in the instant claims. Even assuming that FDSCs of Huang et al. are not fibroblasts, the claimed fibroblasts with the phenotypes of CD73(+), CD90(+), CD105(+) and/or CD45(-) are still obvious to one of ordinary skill in the art, because these phenotypes are common features of fibroblasts, as evidenced by fibroblasts of Denu or Balducci, and by Hs68 fibroblasts of Huang et al. Finally, it is noted that Applicant’s arguments based on not all fibroblasts express CD73, CD90, and/or CD105 in pages 9-10 are not persuasive for the reasons indicated above.
In response to Applicant’s arguments based on motivation in the 01/20/2026 response (pages 10-11), one of ordinary skill in the art would have been motivated to apply fibroblasts having the phenotypes of CD73(+), CD90(+), CD105(+) and/or CD45(-) in the method suggested by Chen and other cited prior art for BDNF transfection and further administration into a patient for inducing regeneration or healing response in the brain suffered from stroke, because fibroblasts with phenotypes of CD73+, CD105+, CD90+ and CD45- are well established and readily available in the art, with the advantages of easy access and propagation; and they are commonly used in the art as paradigms of fibroblasts, as supported by Denu. Furthermore, regardless of whether Huang presented evidence that fibroblasts differentiate into neural cells, Chen et al. demonstrate that administration of fibroblasts leads regeneration of the brain, which results in less brain tissue loss, more surviving neurons, and enhancing functional restoration. Thus, the claimed method would have been obvious over the combined teachings of the cited prior art.
Applicant's arguments about the rejection of claims 1, 9-13, 16, and 18-23 in the response filed on 01/20/2026 (pages 11-12) have been fully considered but they are not persuasive. Examiner notes that inflammation possibly caused by fibroblasts in organs such as GI tract, skin, and joints is not relevant to fibroblasts delivered into the CSF by a intrathecal route taught by Lim et al., because these delivered fibroblasts cannot be released to the organs for inducing inflammation due to the presence of the blood-brain barrier. The claims would have been obvious over the cited prior art for all the reasons indicated above.
Applicant’s arguments based on phenotypes of CD90 and CD105 in the section D of the 01/20/2026 response (page 13) have been fully considered, but are not persuasive for the reasons indicated above. Examiner reminds Applicant that none of the claims 1, 9-13, 16, 18, and 21-23 recite any imitation to require selection of fibroblasts expressing CD90 and CD105 from an unsorted population of fibroblasts. Overall, claims 13 and 16 would have been obvious over the cited prior art for all the reasons indicated above.
Applicant’s arguments based on new claims 27-28 in the section E of the 01/20/2026 response (page 13) are moot because they are not rejected under 35 U.S.C. 103. As indicated above, the subject matter of the claims are free of the art.
Applicant’s arguments in the section F of the 01/20/2026 response (pages 14-17) have been fully considered, but are not persuasive. In response to Applicant’s arguments in the section F of the 01/20/2026 response (pages 14-16), Examiner points out that the fibroblasts used in the claimed method of claim 1 are not limited to fibroblasts selected for enrichment of expressing CXCR4 or any other surface markers; and the claim 1 does not recite any limitation for enriching fibroblasts in the claimed method. With regard to Applicant’s remaining arguments in page 14/para 1, they are misleading and not persuasive. It is noted that although tumor cells use regulation pathways of normal cells (including CXCR4 pathway) for promoting their cell proliferation, CXCR4 itself is not a carcinogen agent and CXCR4 is important for performing function of normal cells (non-tumor cells). Furthermore, Fibroblasts are not tumor cells either. Given Chen demonstrates fibroblasts are safe for being delivering to the brain, one of ordinary skill in the art would have been motivated to modify the method of Chen et al. by introducing CXCR-4 into the fibroblasts because of its important roles in repairing injure after stroke as taught by the cited prior art. With regard to Applicant’s arguments based on the teachings of Balducci in pages 14-15, they are not persuasive. Regardless of whether MSCs and fibroblasts are different or have different characteristics, it is well known in the art that fibroblasts have phenotypes of CD73+, CD105+, CD90+ and CD45-, as evidenced by Balducci et al. and Denu et al. The fibroblasts with the claimed phenotypes used in the claimed method would have been obvious over the cited prior art, as indicated above.
In response to Applicant’s additional arguments in the section F of the 01/20/2026 response (pages 15-16), the teachings of Ichim indicate that fibroblasts may be utilized as a more practical and more effective cell therapy than mesenchymal stem cells (abstract/lines 7-8), and investigators demonstrated similar expression patters for CD45(-), CD105(+), CD73(+), and CD90(+) between the stem cells and fibroblasts (see last para of page 3). The situation of ”in some case” taught by Ichim is certainly appliable to the method of Chen, because Chen utilized fibroblasts as an effective cell therapy in replacement of MSCs for treating stroke. it would have been obvious to apply fibroblasts having CD73+, CD105+, CD90+ and CD45- phenotypes for treating an individual suffered from a stroke for all the reasons indicated above. Applicant’s arguments based on the office has not established MSCs share functional characteristics with fibroblasts are moot, because Chen already successfully established the method of using fibroblasts as an effective and practical cell therapy.
With regard to Applicant’s arguments based on CXCR4-CXCR12 interaction in pages 16-17 of the response, it is noted that using antibodies to neutralize CXCL12 as well as sequestration of CXCL12 in cancer cells are not relevant to the method of using fibroblasts for treating stroke suggested by Chen, because there is no use of antibody or involvement of cancer cells in Chen’s method. Furthermore, it is common knowledge that a ligand’s expression can be upregulated for producing sufficient ligand when there is a need for regular cell function. One of ordinary skill in the art would reasonably expect that introducing CXCR-4 into fibroblasts would facilitate repairing injure after stroke.
Overall, the conclusion of the obviousness of the claims 1, 5, 9-13, 16, 18-23 has been established for all the reasons indicated above.
Applicant’s arguments about the double patenting rejections in the section G of the 01/20/2026 response (pages 17-19) have been fully considered, but they are not persuasive. As indicated above, the cited prior art provides the motivation for administering fibroblasts expressing CD73 and CXCR4 as claimed. It is also noted Applicant’s arguments in page 19/para 2 are moot because the instant claims are not at allowable condition. Thus, the instant claims would have been obvious over the claims of cited copending U.S. applications in combined with the cited prior art for all the reason indicated above.
Conclusion
No claim is in condition for allowance.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Qing Xu, Ph.D., whose telephone number is (571) 272-3076. The examiner can normally be reached on Monday-Friday from 9:30 AM to 5:00 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath N. Rao, can be reached at (571) 272-0939. Any inquiry of a general nature or relating to the status of this application or proceeding should be directed to the receptionist whose telephone number is (571) 272-1600.
/Qing Xu/
Patent Examiner
Art Unit 1656