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 .
Claims 5, 7, 15, 19, 20, 24, 41, 46, 54, 56, 60-63, 68 and 70 are pending in this application and were examined on their merits.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 11/20/2025 has been entered.
Response to Amendment
The Declaration under 37 CFR 1.132 filed 11/20/2025 is insufficient to overcome the rejection of claims 5, 7, 15, 19, 20, 24, 41, 46, 54, 56, 60-63, 68 and 70 based upon at least Peak et al. (04/09/2018), as evidenced by Thoma (2015) as set forth in the last Office action because:
The Declaration presents evidence of the unexpected superiority of exosomes from CH-MSC (with and without miR-124) in killing PD-L1 positive cancer cells as compared to killing PD-L1 negative/low cancer cells (Declaration, Pgs. 1-3).
This is not found to be persuasive for the following reasons, the Declarant’s allegations of unexpected results are not commensurate in scope with the claimed invention. That is, the declaratory results are drawn to the unexpected superiority of exosomes from CH-MSC (with and without miR-124) in killing PD-L1 positive high lung/breast cancer cells as compared to killing PD-L1 negative/low lung/breast cancer cells in vitro. This is not reflected in the instant claims which are drawn generally to “treating PD-L1 positive cancer” and does not require the PD-L1 cancer be “high” or that the treatment is less effective against PD-L1 negative or “low” cancers. The Examiner further notes that the claims are not limited to PD-L1 cancer of any particular organ, much less the lung or breast of the Declaration. The declaratory data further require administration of a particular amount of exosomes (5x108) to achieve the effect while the claims do not require any particular amount of exosomes be administered in the pharmaceutical composition.
Finally, the declaratory data is a measurement of the relative proliferation of cancer cells (Pg. 3, Fig. X1), however the Declarant asserts that a reduction of relative cell proliferation is a correlative measure of cell death. The two processes are not necessarily correlative such that the ordinary artisan would readily comprehend that a reduction if relative cell proliferation is equated to an increase in cell death. A reduction in cell number could indicate that the cells have stopped growing and/or are growing more slowly not that the cells are necessarily dead or dying at an increased rate.
Claim Rejections - 35 USC § 103
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.
Claim(s) 5, 60 and 68 are rejected under 35 U.S.C. § 103 as being
unpatentable over Peak et al. (04/09/2018), as evidenced by Thoma (2015), both of
record, as necessitated by Applicant’s amendments to the claims filed 07/02/2025.
Peak et al. teaches isolating and culturing placenta-derived stem cells (PLSC)
from chorionic tissue of the placenta (therefore devoid of amniotic placenta MSC and
exosomes thereof) (Pg. 1005, Column 1, Lines 24-26);
wherein PLSC are a form of MSC (Pg. 1004, Column 2, Lines 12-14);
isolating exosomes (reading on a composition “consisting of’) from said PLSC
Pg. 1005, Column 1, Lines 57-58);
and contacting prostate cancer (PCa) cells with said isolated exosomes wherein
the treatment reduced PCa viability but did not affect non-tumorigenic cells (Pg. 1007,
Fig. 3), and reading on Claims 5, 60 and 68.
The reference further suggests the use of PLSC exosomes in in vivo tumor
models (Pg. 1009, Column 1, Lines 42-44).
The Specification as filed at Paragraph [0050] indicates that prostate cancer is a PD-L1 cancer. Further, Thoma evidences that PD-L1 is expressed in tumors of greater than 50% of patients with primary prostate cancer (Column 1, Lines 1-6).
The teachings of Peak et al. were discussed above.
Peak et al. did not teach a method of selecting a subject suffering from a PD-L1 positive cancer and administering to the selected subject a pharmaceutical composition comprising exosomes from CH-MSC, as required by Claims 5 and 68;
or wherein the administered pharmaceutical composition consists of exosomes from CH-MSC, as required by Claim 60.
It would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Peak et al. of treating PD-L1 prostate cancer cells in vitro with a pharmaceutical composition consisting of CH-MSC exosomes to select and treat a subject with PD-L1 cancer with CH-MSC exosomes because the reference suggests the use of the treatment in in vivo models. Those of ordinary skill in the art would have been motivated to make this modification in order to establish whether an in vitro PD-L1 prostate cancer treatment would also be effective against PD-L1 prostate cancer in vivo. There would have been a reasonable expectation of success in making this modification because the reference teaches an in vitro treatment and suggests its use in vivo.
Claim(s) 5, 24, 60 and 68 are rejected under 35 U.S.C. § 103 as being unpatentable over Peak et al. (04/09/2018), as evidenced by Thoma (2015), as applied to Claims 5, 60 and 68 above, and further in view of Yuan et al. (2017), all of record.
The teachings of Peak et al. were discussed above.
Peak et al. did not teach a method wherein the CH-MSC exosomes express the anti-cancer therapeutic MTRAIL, as required by Claim 24.
Yuan et al. teaches MSC derived exosomes expressing TRAIL is an effective anticancer therapy (Pg. 1, Abstract) and that MSCTRAIL-derived EVs/exosomes express membranal TRAIL (Pg. 4, Column 2, Lines 34-50).
It would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Peak et al. of treating PD-L1 prostate cancer in vivo with a pharmaceutical composition consisting of CH-MSC exosomes to modify those exosomes to additionally comprise MTRAIL as taught by Yuan et al. because this would provide the anti-prostate cancer CH-MSC exosomes of Peak et al. with an additional anti-cancer treatment. Those of ordinary skill in the art would have been motivated to make this modification in order to provide a combined treatment against PD-L1 prostate cancer in vivo. There would have been a reasonable expectation of success in making this modification because both Peak and Yuan are drawn to the same field of endeavor, that is, the use of MSC exosomes as cancer treatments.
Claim(s) 5, 54, 56, 60 and 68 are rejected under 35 U.S.C. § 103 as being unpatentable over Peak et al. (04/09/2018), as evidenced by Thoma (2015), as applied to Claims 5, 60 and 68 above, and further in view of Vanacore et al. (2017), all of record.
The teachings of Peak et al. were discussed above.
Peak et al. did not teach a method further comprising administering at least one anticancer treatment, as required by Claim 54;
or wherein the anticancer treatment is irradiation, as required by Claim 56.
Vanacore et al. teaches that radiation therapy is the main local disease treatment after surgery while treatment of advanced prostate cancer is founded on chemotherapy (Pg. 50241, Column 1, Lines 40-41 and 53-55).
It would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Peak et al. of treating PD-L1 prostate cancer in vivo with a pharmaceutical composition consisting of CH-MSC exosomes to modify those exosomes to additionally administer a conventional prostate cancer treatment such as radiation or chemotherapy as taught by Vanacore et al. because this would provide the anti-prostate cancer CH-MSC exosomes of Peak et al. with an additional known anti-prostate cancer treatment. Those of ordinary skill in the art would have been motivated to make this modification in order to provide a combined treatment against PD-L1 prostate cancer in vivo. There would have been a reasonable expectation of success in making this modification because both Peak and Vanacore are drawn to the same field of endeavor, that is, prostate cancer treatments.
With regard to the limitation of Claim 56, that the combined treatment: a) sensitize said PD-L1 positive cancer to irradiation, chemotherapy or both, b) protect healthy cells from said irradiation, chemotherapy or both, or c) both a) and b), this is an inherent feature of the claimed method and the prior art which teaches administration of the same treatment as claimed to the same population. Therefore, the results would be the same. This is evidenced by the Specification as filed at Pg. 17, Paragraph [0102] which states:
“In some embodiments, the MSC, extracellular vesicles, miRs, pre-miRs, mimics or combinations thereof sensitize the cancer to at least one anti-cancer therapy. In some embodiments, the MSC, extracellular vesicles, miRs, pre-miRs, mimics or combinations thereof sensitize the cancer to irradiation.
In some embodiments, the MSC, extracellular vesicles, miRs, pre-miRs, mimics or combinations thereof sensitize the cancer to chemotherapy. In some embodiments, the MSC, extracellular vesicles, miRs, pre-miRs, mimics or combinations thereof protect a healthy cell form irradiation, chemotherapy or both”.
Thus, the CH-MSC exosomes of Peak et al. would also be expected to sensitize cancer (glioma) cells to radiation while protecting normal cell from irradiation.
Claim(s) 5, 7, 60, 68 and 70 are rejected under 35 U.S.C. § 103 as being unpatentable over Peak et al. (04/09/2018), as evidenced by Thoma (2015), as applied to Claims 5, 60 and 68 above, and further in view of Lang et al. (2017) and Shi et al. (2013), all of record.
The teachings of Peak et al. were discussed above.
Peak et al. did not teach wherein the exosomes from CH-MSC comprise miR- 124, as required by Claims 7 and 70.
Lang et al. teaches that MSCs can be transduced with lentivirus vectors containing miR-124a and isolating vesicles (exosomes) containing miR-124a from the medium (Pg. 381, Abstract).
Shi et al. teaches that miR-124 can inhibit the growth of prostate cancer cells in vitro and in vivo (Pg. 4130, Abstract).
It would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Peak et al. of treating PD-L1 prostate cancer in vivo with a pharmaceutical composition consisting of CH-MSC exosomes to modify those exosomes to additionally comprise miR-124a as taught by Lang et al. because this would provide the anti-prostate cancer CH-MSC exosomes of Peak et al. with an additional anti-prostate cancer treatment, as taught by Shi et al. above. Those of ordinary skill in the art would have been motivated to make this modification in order to provide a combined treatment against PD-L1 prostate cancer in vivo. There would have been a reasonable expectation of success in making this modification because both Peak and Lang are drawn to the same field of endeavor, that is, the use of MSC exosomes as cancer treatments.
Claim(s) 5, 7, 15, 19, 20, 41, 46, 60, 61, 62, 63, 68 and 70 are rejected under 35 U.S.C. § 103 as being unpatentable over Peak et al. (04/09/2018), as evidenced by Thoma (2015), in view of Lang et al. (2017, as applied to Claims 5, 7, 60, 68 and 70 above, and further in view of Bader et al. (US 2014/0378528 A1) and Kao et al. (2014), all of record.
The teachings of Peak et al. and Lang et al. were discussed above.
Neither Peak et al. or Lang et al. taught wherein the CH-MSC exosomes comprise miR-34 and miR-30b, as required by Claims 15, 19, 41, 61, 62 and 63.
Bader et al. teaches treating a subject with prostate cancer with miR-34 (Pg. 24, Claims 1-2).
Kao et al. teaches that lentiviral expression of miR-30b in prostate cancer cells inhibits invasion, migration and Epithelial-to-Mesenchymal transition (EMT) (Pg. 2496, Column 2, Lines 23-25 and 53-56 and Pg. 2499, Fig. 3).
It would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Peak et al. and Lang et al. of treating PD-L1 prostate cancer in vivo with a pharmaceutical composition consisting of CH-MSC exosomes comprising miR-124a with the modification of the exosomes to comprise miR-34 and miR-30b as taught by Bader et al. and Kao et al. respectively because this would provide the anti-prostate cancer CH-MSC exosomes of Peak et al. and Lang et al. with additional anti-prostate cancer treating miRs. Those of ordinary skill in the art would have been motivated to make this modification in order to provide a combined treatment against PD-L1 prostate cancer in vivo. There would have been a reasonable expectation of success in making this modification because both Peak is drawn to the use of MSC exosomes as cancer treatments, Lang is drawn to the use of MSC exosomes comprising a miR as a cancer treatment and Bader and Kao teach particular miRs as suitable treatments for prostate cancer.
With regard to Claims 20 and 46, the Specification as filed at Paragraph [0050]
indicates that prostate cancer is a PD-L1 cancer. Further, Thoma evidences that PD-L1
is expressed in tumors of greater than 50% of patients with primary prostate cancer
(Column 1, Lines 1-6).
Response to Arguments
Applicant's arguments filed 11/20/2025 have been fully considered but they are not persuasive.
The Applicant cites the Declaration as providing unexpected results over the Peak reference (Remarks, Pg. 3, Lines 8-13).
This is not found to be persuasive for the reasoning provided in the Response to Amendment above, that is, the showing of unexpected results is not commensurate in scope with the claimed invention.
The Applicant argues that Peak teaches PLSC and states that PLSCs are one of various forms of MSC but does not state that PLSCs are devoid of other cell types. Applicant notes the PLSC were isolated according to De Coppi which Applicant alleges contains other cell types and would have led Peak to name the cells PL-MSC instead of PLSC and asserts the cells of Peak would contain other cell types besides MSC (Remarks, Pg. 3, Lines 14-29 and Pg. 4, Lines 1-9).
This is not found to be persuasive for the following reasons, as discussed in the prior action and above, Peak teaches isolating and culturing placenta-derived stem cells (PLSC) from chorionic tissue of the placenta (therefore devoid of amniotic placenta MSC and exosomes thereof) (Pg. 1005, Column 1, Lines 24-26); wherein PLSC are a form of MSC (Pg. 1004, Column 2, Lines 12-14); isolating exosomes (reading on a composition “consisting of’) from said PLSC (Pg. 1005, Column 1, Lines 57-58). The claims only require the composition consists of EVs from CH-MSC. Applicant has not provided evidence that the isolated chorionic PLSC-MSC population necessarily contains other cell types or that these cell types necessarily produce EVs. Thus, the Examiner maintains that the isolated chorionic PLSC-MSC of Peak from which EVs were then isolated would anticipate the limitations of instant Claim 60.
The Applicant argues that the Examiner’s interpretation that prostate cancer is a PD-L1 positive cancer in light of the teachings in the Specification is incorrect. Applicant opines that the Specification as filed which states at Pg. 6, Paragraph [050]:
“According to some embodiments, the PD-L1 positive cancer is selected from a brain cancer cell, a lung cancer cell, a breast cancer cell, a melanoma cell, a meningioma cell, a pancreatic cancer cell, a prostate cancer cell, a medulloblastoma cell, a glioma cell and a metastatic cell of a brain cancer”,
means that in some embodiments the PD-L1 positive cancer is prostate cancer not that all prostate cancers are PD-L1 positive. Applicant asserts that no type of cancer is always PD-L1 positive or negative and therefore all prostate cancers cannot be PD-L1 positive.
Applicant notes that Peak tested both PD-L1 positive and negative cancers and did not differentiate a difference in the treatment thereof (Remarks, Pg. 4, Lines 10-23).
This is not found to be persuasive for the following reasons, as discussed above,
Peak teaches treatment of prostate cancer cell lines (one of which was known in the art
to be PD-L1 positive before the time of the invention, CWR-R1-R, as evidenced by Martin, of record) and C4-2B-R (which inherently is PD-L1 positive, as evidenced by Xu, of record). Peak further suggests the use of PLSC exosomes in in vivo tumor models. At the time of the invention, PD-L1 was known to be expressed in tumors of greater than 50% of patients with primary prostate cancer (see Thoma, of record), thus motivating the ordinary artisan to select a subject with the prevalent cancer phenotype. The instant Specification acknowledges that in some embodiments, prostate cancer is a PD-L1 cancer. Thus, those of ordinary skill in the art would have been motivated to apply the in vitro treatment of Peak in vivo in order to establish whether an in vitro PD-L1 prostate cancer treatment would also be effective against PD-L1 prostate cancer in vivo.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to PAUL C MARTIN whose telephone number is (571)272-3348. The Examiner can normally be reached Monday-Friday 12pm-8pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, Applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Sharmila G Landau can be reached at (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL C MARTIN/Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653