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 .
This action is responsive to papers filed 03/24/2026.
Claim 1 has been amended.
No claims have been newly added or newly canceled.
Claims 1, 7-9, 13, 16, 19-20, 22-23, 25, 32-33, 35, 37, 39-41, 50-51, 54-56, 59 and 62 are currently pending.
Claims 19-20, 22-23, 25, 41, 54-56 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/27/2025.
Claims 1, 7-9, 13, 16, 32-33, 35, 37, 39-40, 50-51, 59, and 62 have been examined
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn due to amendment. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 16, 37, 51 and 62 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Cowan et al (WO 2017/109757-from IDS filed10/17/2022).
Regarding claim 1, Cowan disclose a method for treating a patient with frontotemporal dementia (FTLD) by creating a patient specific iPSC by isolating a somatic cell from the patient wherein the somatic cell is a fibroblast and implanting the cell derived from that fibroblast into the patient (pages 160-161, claims 3-5).
Regarding claim 16, Cowan disclose wherein FTLD is associated with the destruction of neurons (neuronal cell death and apoptosis) (page 36 para 225).
Regarding claim 37, Cowan disclose wherein their method includes exosomes (page 170 claim 68).
Regarding claim 51, while Cowan are silent with regard to the capability of the fibroblasts and/or fibroblast-derived products on the stimulation of HUVEC cells, stimulation of astrocyte production of VEGF or stimulation of astrocyte production of SDF-1, these are deemed to be inherent capabilities of the fibroblasts and/or fibroblast-derived products baring evidence to the contrary depending on their intended use or modifications (page 28 para 190).
Regarding claim 59, Cowan disclose wherein the genetically modified cells are injected directly into the patient’s nervous system (page 101 para 482).
Regarding claim 62, Cowan disclose wherein the cells (derived from the somatic cell, fibroblast) administered to the patient are hematopoietic progenitor cells or neural cells (page 160, claims 3-5). These cells inherently express CD105 or are present on their surface.
Therefore, the teaching of Cowan et al anticipates Applicant’s invention as claimed.
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.
Claim(s) 1, 32-33, 35, 51 and 59 are rejected under 35 U.S.C. 103 as being unpatentable over Lande et al (WO 2018/049079) in view of Hutton et al (WO 2008/019187).
Regarding claims 1, 32-33, 35, 59, Lande disclose methods and compositions for modulating gene expression (Title, abstract). In some embodiments cells may be excised from a subject and gene expression altered prior to transplantation of the cells back into a subject wherein the cells include fibroblasts (page 97 lines 21-25). These methods include treatment of neurological diseases or disorders including frontotemporal dementia (page 115 lines 4-15). Modes of administration include inject, intravenous, intraspinal and system (contact with subject’s vasculature and/or nervous system) (page 101 lines 20-32).
Lande do not specifically disclose an embodiment with a fibroblast or fibroblast-derived product administered to a subject with frontotemporal dementia.
Hutton disclose methods of treating dementia by administering compositions comprising a nucleic acid encoding a progranulin (PGRN) polypeptide to a subject such that the level of a PGRN polypeptide is increased in the subject (page 3 lines 24-29) and the symptoms can improve by at least 25% (page 7 lines 3-11). The type of dementia includes frontotemporal dementia (page 7 lines 15-16). The nucleic acid encoding PGRN polypeptide can be administered using a viral vector (page 7 lines 15-24).
One of ordinary skill in the art would have been motivated to genetically modify cells such as fibroblasts with a nucleic acid encoding PGRN for administration in the method of Lande for the treatment of frontotemporal dementia because Hutton teach and suggest that increasing the expression of PGRN nucleic in a subject with frontotemporal dementia provides symptom improvement by at least 25%. One of ordinary skill in the art would have had a reasonable expectation of success because Hutton disclose methods and compositions for the providing the nucleic acid encoding PGRN polypeptide and Lande indicate that fibroblast cells can be genetically modified for the treatment of frontotemporal dementia.
Regarding claim 51, while Lande and Hutton are silent with regard to the capability of the fibroblasts and/or fibroblast-derived products on the stimulation of HUVEC cells, stimulation of astrocyte production of VEGF or stimulation of astrocyte production of SDF-1, these are deemed to be inherent capabilities of fibroblasts and/or fibroblast-derived products, baring evidence to the contrary, depending on their potential modifications.
Therefore, the combined teachings of Lande et al and Hutton et al render obvious Applicant’s invention as claimed.
Claim(s) 7-9, 13 and 50 are rejected under 35 U.S.C. 103 as being unpatentable over Lande et al (WO 2018/049079) in view of Hutton et al (WO 2008/019187) as applied to claims 1, 32-33, 35, 51 and 59 above, and further in view of O’Heeron et al (US 2018/0195044) and Matsuyama et al (WO2018/110686).
Regarding claims 7-9, 13 and 50, the combined teachings of Lande et al and Hutton et al render obvious Applicant’s invention as described above, but do not specifically teach including treating the fibroblasts or fibroblast-derived products with one or more compositions capable of activating NF-kappa B or wherein the fibroblasts or fibroblast-derived products are angiogenic.
O’Heeron disclose methods of enhancing fibroblast therapeutic activity (Title). O’Heeron disclose that any particular therapeutic activity of fibroblasts may be enhanced upon one or more exposures to one or more biologically active substance and/or one or more conditions and the activity is anti-inflammatory, angiogenic, and/or regenerative (page 2 para 18) by culturing the fibroblasts with growth factors (page 2 para 20). The growth factors can include interleukin-1 and TNF and combinations thereof (page 3 para 30).
Matsuyama disclose pharmaceutical compositions useful for healing and repairing diseased tissue comprising adherent cells derived from mesenchymal tissues treated with a polypeptide, wherein the polypeptide is one or more of interleukin-1 and TNF-alpha (page 4).
One of ordinary skill in the art would have been motivated to treat the fibroblasts of Lande with interleukin-1 and/or TNF-alpha (activating NF-kappa B and endowing them with abilities such as those claimed) because O’Heeron and Matsuyama teach and suggest that it is suitable and beneficial to treat cells, such as fibroblasts, with these growth factors to enhance their therapeutic activity to repair and regenerate damaged tissue. One of ordinary skill in the art would have been motivated to treat the fibroblasts and/or fibroblast-derived products such that they are angiogenic because O’Heeron suggest that this is desirable and beneficial for the treatment of damaged tissue. One of ordinary skill in the art would have had a reasonable expectation of success because Lande suggest that their cells can be treated to improve their therapeutic effect and fibroblasts are a mesenchymal cell type.
Therefore, the combined teachings of Lande et al, Hutton et al, O’Heeron et al and Matsuyama et al render obvious Applicant’s invention as claimed.
Claim(s) 1, 16, 37, 39-40 are rejected under 35 U.S.C. 103 as being unpatentable over Cowan et al (WO 2017/109757-from IDS filed10/17/2022) as applied to claims 1, 16, 37, 51 and 62 above, and further in view of Becker et al (WO 2020/061404) and Wang et al (Neuroscience 2015).
Regarding claims 1, 16, and 37, Cowan disclose a method for treating a patient with frontotemporal dementia (FTLD) by creating a patient specific iPSC by isolating a somatic cell from the patient wherein the somatic cell is a fibroblast and implanting the cell derived from that fibroblast into the patient (pages 160-161, claims 3-5). Cowan disclose wherein their method includes exosomes (page 170 claim 68). Cowan disclose wherein FTLD is associated with the destruction of neurons (neuronal cell death and apoptosis) (page 36 para 225).
Cowan do not specifically describe an embodiment for treating FTLD with a fibroblast-derived product comprising exosomes or apoptotic vesicles derived from fibroblasts or the use of phosphatidylserine and Annexin V.
Becker disclose compositions and methods for inhibiting brain trauma induced neurodegeneration and related conditions (Title), particularly the treatment of conditions such as dementia involving programmed neuronal loss (neuronal apoptosis) (pages 2-3 para 7, pages 3-5 para 10-12). Becker also disclose that biomarkers and/or diagnostic criteria of anecrotic cell death may be monitored to determine the efficacy of treatment and that cellular changes can be observed to occur during the process that leads to anecrotic or preprogrammed cell death (apoptotic cell death) in exosomes through the changed expression of key proteins involved in cellular dysfunction and death (page 24 para 103). The antibody Annexin V strongly binds with phospholipid phosphatidylserine (PS) and its detection has been widely used for imaging of anecrotic or preprogrammed cell death both in cellular studies and in vivo, including humans and imaging of externalized PS using Annexin V is one non-limiting example or means for monitoring hallmarks of anecrotic cell death to determine the efficacy of treatment (pages 24-25 para 103).
Wang teaches that there are numerous causes for frontotemporal dementia (FTD) including traumatic brain injury (abstract).
Therefore, one of ordinary skill in the art would have been motivated with a reasonable expectation of success to include fibroblast-derived exosomes that comprise or express phosphatidylserine along with Annexin V in the Cowan method because Becker teach and suggest that this is beneficial and desirable for the monitoring apoptotic neuronal cell death during dementia treatment caused by brain trauma and Wang teach that frontotemporal dementia can be caused by brain trauma.
Therefore, the combined teachings of Cowan et al, Becker et al and Wang et al render obvious Applicant’s invention as claimed.
Response to Arguments
Applicant's arguments filed 03/24/2026 have been fully considered but they are not persuasive. Applicant’s arguments have been addressed in so far as they relate to the rejections above.
Applicant argues that the Cowan reference method does not teach a method of treating frontotemporal dementia by administering fibroblasts or fibroblast-derived products and points to paragraphs 22 and 247 and claims 3-5 as evidence that Cowen is administering pluripotent stem cells instead.
This is not found persuasive. The cell that Cowan is administering to the frontotemporal dementia patient is a cell that has been derived from a fibroblast and is thus deemed to be a fibroblast-derived product. While Applicant has cited examples of fibroblast-derived products in their Specification, there is no definitive recitation of a definition of what encompasses a “fibroblast-derived product” and therefore this limitation has been given its broadest reasonable interpretation consistent with the art of cell therapy as any product that has been derived from a fibroblast. Since the cells administered in the Cowen method have been derived from a fibroblast they are deemed to meet this interpretation of a fibroblast-derived product and thus anticipate Applicant’s invention as claimed.
Applicant argues that it is self-evident that the skilled artisan would have no need to consider the teachings of the combined cited references of Lande and Hutton because of their incompatible teachings. Applicant asserts that their combined disclosures instruct the skilled artisan to utilize either a PGRN polypeptide or a nucleic acid or a site-specific targeting moiety and an epigenetic modifying agent. Applicant asserts that this combination is not instructive which to utilize to treat frontotemporal dementia and impermissible hindsight is being used here. Applicant asserts that in particular one cannot use hindsight reconstruction to pick and choose among isolated disclosures in the prior art to deprecate the claimed invention and point to In re Fine and W.L. Gore & Assocs., Inc v Garlock, Inc as evidence.
This is not found persuasive. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
In addition, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
In the current case, Lande teach using fibroblasts that have been genetically modified to treat illness and diseases, such as frontotemporal dementia, and Hutton disclose that there are genetic constructs that can be incorporated into treatments for frontotemporal dementia.
Applicant argues that Lande in combination with Hutton fails to disclose fibroblasts or fibroblast-derived products for an individual with frontotemporal dementia. Applicant argues that Hutton in combination with Lande states that any appropriate cell type can be used to identify or characterize agents that can increase the level of PGRN polypeptide and treat dementia, including Chinese Hamster Ovary cells, fibroblasts, neuronal cells, lymphoblast cells or neuroglioma cells at page 43. Applicant argues again that the examiner is using hindsight reasoning for combining these references having unrelated disclosures.
This is not found persuasive. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
In the current case fibroblasts are a well-known commonly used cell type in the field of cell therapy and clearly shown to be an option from the cited prior art.
Applicant argues that O’Heeron and Matsuyama fail to address the failings of the combination of Lande and Hutton.
This is not found persuasive. The combination of Lande and Hutton is not deemed to be defective.
Applicant argues that any combination that includes Cowan cannot render the claim obvious because Cowan is limited to the treatment of ALS or frontotemporal dementia with cells that are not fibroblasts and asserts that this is a required element in the presently claimed invention.
This is not found persuasive. The claims require either fibroblasts and/or fibroblast-derived products. Since any product derived from a fibroblast that has a therapeutic effect when administered into patients with frontotemporal dementia can meet the requirements of the claims and Cowen recites such a fibroblast-derived product as described above, the claim requirements are deemed to be met.
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Crabtree et al., “MicroRna Mediated Neuronal Cell Induction”, WO 2013/089819, (Discloses treatment of neurodegenerative diseases, such as frontotemporal dementia, by administering fibroblast-derived products, see page 2 lines 15-21, page 9 lines 7-18, page 24 lines 6-20, page 26, page 28, , page 31 lines 3-14).
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA J SCHUBERG whose telephone number is (571)272-3347. The examiner can normally be reached 8:30-5:00 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James (Doug) Schultz can be reached at 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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LAURA J. SCHUBERG
Primary Examiner
Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631
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