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 .
Priority
This application is a 371 of PCT/US2022/013663 01/25/2022 which claims benefit of 63/141,665 01/26/2021.
Election/Restrictions
Applicant’s election without traverse of Group 1, claims 1 and 3-10 in the reply filed on 14 October 2025 was previously acknowledged.
Claims 13, 15, 17, 20-21, 40-46, and 48 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 14 October 2025.
Claim Status
Claims 2, 11-12, 14, 16, 18-19, 22-24, 26-39, 47, and 49-51 were previously canceled, claim 1 is currently amended, claims 13, 15, 17, 20-21, and 40-41 have been withdrawn from further consideration, and claims 1 and 3-10 have been considered on their merits.
Withdrawn Rejections
The claim rejections under 35 U.S.C. §102 have been withdrawn due to Applicant’s amendment the claim as the previous rejection did not address the new limitation. However, a substantially similar rejection is set forth below utilizing the same references.
The claim rejections under 35 U.S.C. §103 have been withdrawn due to Applicant’s amendment the claim as the previous rejection did not address the new limitation. However, a substantially similar rejection is set forth below utilizing the same references.
Claim Interpretation
Claim 1 recites the limitation “substantially homogenous” in reference to a cancerous mammalian cell population. The instant specification, at p. 24 para. [0096], states "Substantially homogenous" refers to a population of cells derived from the same mammalian organ or region of a mammalian organ wherein the majority between about 100% to about 70%; between about 100% to about 90% of the total number of cells have a specified characteristic of interest. The disclosure of cells having a specified characteristic of interest is very broad to include any characteristic of a cell, to include cell type. For example, a population of fibroblasts from a breast tumor reads as substantially homogenous because the population of cells are all fibroblasts, which reads as a morphological characteristic.
The instant specification, at p. 15 para. [0065], states "Cancer" or "tumor" or "cancerous" are well known in the art and refer to the presence, e.g., in a subject, of cells possessing characteristics typical of cancer-causing cells, such as uncontrolled proliferation, immortality, metastatic potential, rapid growth and proliferation rate, decreased cell death/apoptosis, and certain characteristic morphological features.
Therefore, “substantially homogenous” is interpreted as referring to a population of cells wherein at least 70% of said population have a characteristic in common.
Regarding the new limitation in amended claim 1, “wherein exosomes are removed from the cell-free conditioned medium (CM) or extract or concentrate thereof.”, the broadest reasonable interpretation of this limitation is, wherein at least some exosomes are removed.
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.
Claims 1 and 3-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Trujillo et al. (WO 2015/120150 A1, IDS ref., of record) as evidenced by Dong et al. (Scientific Reports, 2016, of record), Wang et al. (BioMed Research International, 2019, of record), and Knight et al. (Cellular Signaling, 2019, of record).
This is a new rejection, necessitated by Applicant’s amendments to the claims. A response to Applicant’s traversal follows the new rejection below.
Regarding claims 1 and 3-4, Trujillo teaches compositions comprising tumor-derived exosomes and methods of using the compositions in the treatment of cancer (p. 1, Field of Invention). Trujillo teaches breast tumor cells were rinsed with PBS and human mammary epithelial medium, which comprised DMEM supplemented with glutamine and epidermal growth factor (EGF) (p. 34, Tissue Preparation). Trujillo teaches fibroblasts from the tumor tissue (cancerous mammalian cell population) were grown to confluence, media was replaced, and conditioned media was removed (claim 1) (p. 35, Fibroblast Growth). Trujillo, in Figure 2x, display a population of fibroblasts and associated exosomes, wherein, the figure appears to comprise about 100% fibroblasts (p. 29), in view of the claim interpretation above, the population of fibroblasts read as substantially homogenous. Glutamine and EGF (claim 3) are both small molecules which drive cell proliferation, and thus, activate cell growth signaling, therefore, read as a small molecule activators of cell growth signaling pathways. Regarding the preamble, Trujillo teaches a pharmaceutical composition comprising an exosome according to any one of the embodiments which comprises a pharmaceutically-acceptable vehicle, carrier (claim 4), or excipient (p. 5, 1st para.). Trujillo teaches the factor causing the inhibition of the migration of normal breast epithelial cells can be removed from the conditioned media by centrifugation at 10,000Xg for 45 minutes, conditions typically used to pellet exosomes (p. 29, Example 1 and Fig. 6B). Trujillo teaches utilizing conditioned media with and without exosomes from three patient sample sets of tumor, THAN-1, THAN-3 and THAN-5 fibroblasts (p. 7, Figure 6B description and p. 29, Example 1). Therefore, Trujillo teaches a cell-free CM cultured from a mammalian cell culture medium comprising a cultured substantially homogenous cancerous mammalian cell population wherein the cancerous mammalian cell population is contacted by a small molecule cell growth signaling pathway activator and wherein exosomes are removed from the cell-free CM.
Regarding claims 5 and 6, while Trujillo is silent to specific protein expression profiles of the breast tumor cells, it is known in the art breast cancer cells overexpress and secrete Hsp90ab1, which is also known as Hsp90β, as evidenced by Dong (Dong, p. 2 Results and Fig. 1). Therefore, the conditioned medium would necessarily comprise (claim 5) and be enriched (claim 6) with Hsp90ab1 by the breast cancer cells.
Regarding claim 7, Trujillo teaches exosome-based cancer therapy can be used alone or in combination with a chemotherapeutic (p. 25).
Regarding claim 8, Trujillo teaches breast tumor cells were rinsed with PBS and human mammary epithelial medium, which comprised DMEM supplemented with glutamine and epidermal growth factor (EGF) (p. 34, Tissue Preparation). Glutamine is known in the art to activate the Wnt3a/β-catenin signaling pathway, as evidenced by Wang (Wang, Abstract). EGF is known in the art to activate the β-catenin, a key component of the canonical Wnt signaling pathway as evidenced by Knight (Knight, Abstract). Therefore, the glutamine or EGF of Trujillo teaches the small molecule cell growth signaling pathway activator is a small molecule Wnt signaling pathway activator.
Thus, the reference anticipates the subject matter of claims 1 and 3-8.
Response to Traversal
Regarding the arguments directed to the individual references not correcting the deficiencies of the preceding references, this is not persuasive because, as indicated above, the references utilized are shown to not be deficient.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1 and 3-9 are rejected under 35 U.S.C. 103 as being unpatentable over Trujillo et al. (WO 2015/120150 A1, IDS ref., of record) as evidenced by Dong et al. (Scientific Reports, 2016, of record), Wang et al. (BioMed Research International, 2019, of record), and Knight et al. (Cellular Signaling, 2019, of record) as applied to claims 1 and 3-8 above, and further in view of Ni et al. (In Vitro Cellular & Developmental Biology - Animal (2019), IDS ref., of record).
This is a new rejection, necessitated by Applicant’s amendments to the claims. A response to Applicant’s traversal follows the new rejection below.
Trujillo anticipates the subject matter of claims 1 and 3-8, and thus, also render them obvious.
Regarding claim 9, Trujillo does not teach the small molecule Wnt signaling pathway activator being BML-284.
Ni teaches in Wnt agonist BML-284 treated Wilms tumor-derived cells, G401, increased Apobec-1 complementation factor (A1CF) like other classical regulator of Wnt signal pathway, such as Axin2 and β-catenin (Abstract). Ni teaches A1CF is involved in many cellular processes such as cell proliferation, apoptosis, and migration (Abstract). Ni teaches A1CF promotes cell proliferation and migration and inhibits apoptosis in breast cancer cells (p. 253, Introduction).
Therefore, it would have been obvious to one of ordinary skill in the art to administer BML-284 to the cells of Trujillo prior to culturing the cells in cell culture media with a reasonable expectation of success because Ni teaches A1CF promotes cell proliferation and migration and inhibits apoptosis in breast cancer cells and A1CF is increased by administration of BML-284. One would be motivated to administer BML-284 to the breast cancer cells of Trujillo prior to culturing the cells in cell culture media because promoting cell proliferation and preventing apoptosis would increase the amount of cancerous mammalian cell-secreted proteins from the cancer cells into the conditioned medium.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Response to Traversal
Regarding the arguments directed to the individual references not correcting the deficiencies of the preceding references, this is not persuasive because, as indicated above, the references utilized are shown to not be deficient.
Claims 1, 3-8, and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Trujillo et al. (WO 2015/120150 A1, IDS ref.) as evidenced by Dong et al. (Scientific Reports, 2016, of record), Wang et al. (BioMed Research International, 2019, of record), and Knight et al. (Cellular Signaling, 2019, of record) as applied to claims 1 and 3-8 above, and further in view of Li et al. (Int Rev Cell Mol Biol. 2013).
This is a new rejection, necessitated by Applicant’s amendments to the claims. A response to Applicant’s traversal follows the new rejection below.
Trujillo anticipates the subject matter of claims 1 and 3-8, and thus, also render them obvious.
Regarding claim 10, Trujillo does not teach wherein the cancerous mammalian cells are cancerous mammalian bone cells.
Li teaches tumor cells constitutively secrete Hsp90β, to include breast cancer cells and osteocarcinomas (p. 6, Section 3.2).
Therefore, it would have been obvious to one of ordinary skill in the art to substitute cancerous bone cells for the breast tumor cells of Trujillo in the conditioned medium because both cells would have the equivalent effect of expressing cancerous mammalian cell-secreted proteins. Substitution of one known element for another known element, the elements having equivalent effect, is considered to be obvious, absent a showing that the result of the substitution yields more than predictable results. See MPEP 2143(I).
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Response to Traversal
Regarding the arguments directed to the individual references not correcting the deficiencies of the preceding references, this is not persuasive because, as indicated above, the references utilized are shown to not be deficient.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/N.A.H./Examiner, Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631
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