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 .
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1, 2, 5 and 6) in the reply filed on 1/9/2026 is acknowledged. The election of species is moot as none of the species belong to the elected Group I.
Claims 3-4 and 7-18 have been withdrawn from consideration as being drawn to non-elected subject matter, and claims 1-2 and 5-6 have been considered on the merits.
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) 1-2 and 5-6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Daley et al. (US20010033835A1) in view of Mintz et al. (2014, Molecular Therapy), Sagaradze et al. (2019, Int. J. Mol. Sci.), Vallee et al. (WO86/06079) and Sahoo et al. (2012, Circ. Res.)
Daley et al. teach a method of culturing CD34+ hematopoietic cells using a serum free medium comprising a basal medium, human serum albumin and growth factors (paras. 102, 121, 123-124, 146; Example 2). The CD34+ hematopoietic cells of Daley et al. are considered as progenitor cells or comprise progenitor cells (para.53 and 147). Daley et al. teach that the SFM is StemProTM-34 SFM comprising a basal medium with various supplement (para.107; Table 1). Thus, Daley et al. teach the step (a) of claim 1.
Daley et al. do not teach a step of obtaining conditioned medium from culturing CD34+ hematopoietic cells in a serum-free medium without HSA or growth factors.
Mintz et al. teach the method of producing a conditioned medium (CM) from human CD34+ hematopoietic stem cell using a serum-free medium for using the CM for tissue repair (see entire document; p.150, 1st col.).
It would have been obvious to a person skilled in the art to use the CD34+ hematopoietic cells of Daley et al. to produce conditioned medium for the purpose of utilizing in tissue repair taught by Mintz et al. with a reasonable expectation of success.
Regarding the step (b) directed to removing the first serum-free culture medium from the progenitor cells, it would have been obvious to a person skilled in the art to remove the culture medium utilized for culturing the CD34+ hematopoietic cells of Daley et al. in order to collect conditioned medium of the CD34+ hematopoietic cells of Mintz et al.
Regarding the step (c) directed to culturing the progenitor cells in a second serum-free medium without HSA or growth factors, Daley et al. in view of Mintz et al. do not teach the limitation.
Sagaradze et al. teach that the conditioned medium is collected using basal medium, DMEM-LG (low glucose) or DMEM with NutriStem XF Basal Medium (p.10, 4.3. Collection of MSC conditioned medium). Sagaradze et al. teach that it is important to note that only basal media without nutrimental supplement (FBS or NutriStem supplement) were used for MSC conditioning (p.2, 2.2. Development of MSC-CM Bioprocessing Protocol). Sagaradze et al. compared two basal media for the secreted growth factors or other proteins.
Vallee et al. teach that a method of purifying a protein having an angiogenic activity from a conditioned medium is obtained by culturing cells in serum-free and exogenous protein-free medium (p.29, claim 21). While the cells of Vallee et al. were cultured in a medium (DME; basal medium) comprising FBS for a routine maintenance, these cells were cultured in a DME without FBS for obtaining conditioned medium (Example 1).
It would have been obvious to a person skilled in the art to try using the serum-free basal medium taught by Daley et al. without human serum albumin or growth factors for collecting the CM of the CD34+ hematopoietic cells taught by Mintz et al. A person of ordinary skilled in the art would have been motivated to do so because Sagaradze et al. and Vallee et al. teach the use of a basal medium without any other nutrimental supplement (exogenous protein-free). While the types of cells and culture medium (basal medium) of Sagaradze et al. or Vallee et al. is different from those taught by Daley et al. in view of Mintz et al., however, one skilled in the art would recognize that the protocol for collecting a conditioned medium taught by Sagaradze et al. and Vallee et al. can be applicable to any type of cells. Furthermore, one skilled in the art would understand that the presence of exogenous supplement as the purpose of the collecting/obtaining conditioned medium is to use the cell-secreted factors not the factors added to the culture medium, particularly animal proteins. As serum albumin and growth factors supplemented to the basal medium as taught by Daley et al., one skilled in the art would recognize that in order to obtain a conditioned medium comprising solely those secreted from the cells, these exogenous proteins should be removed from the medium for the conditioned medium as taught by Sagaradze et al. and Vallee et al. Furthermore, one skilled in the art would recognize that such exogenous proteins could introduce unwanted risk of contamination in preparing the conditioned medium as a therapeutic composition or the composition comprising extracellular vesicles including exosomes isolated from the conditioned medium as they are manufactured as a therapeutic composition for their angiogenic activity according to Sahoo et al. (see abstract).
Regarding claim 2 directed to the concentrating or enriching for a small extracellular vesicle-enriched fraction (sEV) from the medium, while Mintz et al. teach the use of conditioned medium for tissue repair, however, it does not disclose that the step of concentrating or enriching the sEV. However, it is also well known in the art that exosomes are isolated from the conditioned medium of CD34+ stem cell and utilized for their proangiogenic paracrine activity according to Sahoo et al. Sahoo et al. teach that CD34+ exosomes are enriched with pro-angiogenic microRNAs (p.4, 2nd para.). It is noted that the exosomes of Sahoo et al. are considered the same as sEV of the instant claims.
It would have been obvious to a person skilled in the art to enrich the conditioned medium of Daley et al. in view of Mintz et al., Sagaradze et al. and Vallee et al. to obtain CD34+ exosomes for therapeutic angiogenesis with a reasonable expectation of success.
Regarding claims 5-6 directed to the therapeutic composition suitable for administration to a patient comprising producing a secretome-containing composition of claim 1 or sEV of claim 2, the combined teachings of the cited references would meet the step of producing a secretome-containing composition or an sEV-containing composition, i.e. conditioned medium or enriched exosomes, as discussed above.
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.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TAEYOON KIM whose telephone number is (571)272-9041. The examiner can normally be reached 9-5 EST Monday-Friday.
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, JAMES 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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/TAEYOON KIM/Primary Examiner, Art Unit 1631