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 .
Applicant's election with traverse of Group I (claims 1-6, 14-15 and 19) in the reply filed on 07/24/2026 is acknowledged. The traversal is on the ground(s) that the teachings of Romanov or Mathen do not specifically teach each and every limitation of claim 1 and asserts that the secretome of claim 1 represents a contribution over the prior art and must constitute a special technical feature. Applicant asserts that this means group I and Group III are unified by this special technical feature. This is not found persuasive because, as shown below, the combined teachings of Mathen, Phan, Romanov et al, Amable et al and Nishida et al render obvious the secretome of claim 1 and thus claim 1 does not make a contribution over the prior art and is not a special technical feature.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-19 are currently pending.
Claims 7-13 and 16-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 07/24/2026.
Claims 1-6, 14-15 and 19 have been examined on their 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) 1-6, 14-15 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Mathen (US 2020/0230172-from IDS) in view of Phan (US 2013/0039893-from IDS), Romanov et al (Cell Technologies in Biology and Medicine 2019-from IDS), Amable et al (Stem Cell Research & Therapy, 2014-from IDS) and Nishida et al (EP 3333254-from IDS).
Regarding claims 1-6, 14-15 and 19, Mathen describes the wound healing activity of Human MSC derived conditioned media. The process for preparing a stem cell conditioned medium for clinical and cosmetic applications comprises cultivating stem cells (UC- or WJ-MSCs) in culture medium to allow the secretion of metabolites selected from the group comprising exosomes, micro-vesicles, soluble proteins, cytokines, chemokines, enzymes, hormones, regulatory and anti-inflammatory factors, signaling molecules and growth factors to obtain stem cell conditioned medium and harvesting the conditioned culture medium (page 2 para 13-17, para 34). In vivo studies were carried out in an animal model of excisional wound healing by MSC derived conditioned media (CM), which showed promising wound healing potential (pages 6-7 Example 4, para 110-111). This stem cell conditioned medium comprises hGCSF (50-1500 pg/ml), hHGF(50-3000 pg/ml), and IL-6 (100 to about 2000 pg/ml) (page 5 para 79-80). The conditioned medium maybe further concentrated by methods known in the art and formulated for therapeutic purposes (page 4 para 72-74).
Mathen does not specifically disclose a therapeutic conditioned medium (secretome) obtained from MSCs of umbilical cord tissue or Wharton’s jelly tissue that contain all the claimed components at the claimed ratios or concentrations.
Phan discloses a microarray for expression profiling analysis of the factors secreted by umbilical cord-MSCs (UCMC) in comparison with BM-MSCs (page 15 para 197). The results of this analysis show that UCMC secrete Interleukin-6 (IL-6); (MCP1); hepatocyte growth factor (HGF); Interleukin-8 (IL8); sTNFR1; GRO; TIMP1; TIMP2; TRAILR3; uPAR; ICAM1; IGFBP3; IGFBP6 (FIG. 11) (pages 15-16 para 198). UCMC were cultured and conditioned media was collected, concentrated and analyzed using a Cytokine Array (page 15 para 197). The gene expression profile showed expression of G-CSF, Angiopoietin (which renders obvious Angiopoietin-like protein 4), Follistatin, MMPs, TIMPs (page 17 para 206). Lysed UCMC were used to prepare a "UCMC extract" which has positive effects on skin keratinocytes and fibroblasts (page 27 para 271). This extract can be prepared for promoting wound healing, skin repair, regeneration and rejuvenation (page 27 para 271).
Romanov measured the production of cytokines and growth factors by cultured human umbilical cord tissue- and bone marrow-derived multipotent mesenchymal stromal cells by multiplex analysis. In most cases, the concentrations of bioactive factors in the culture medium conditioned by umbilical cord-derived cells was ten- to hundred-times higher than in the medium conditioned by bone marrow-derived cells (abstract, page 536-539 Results). In UC-MSC the concentration of some cytokines (IL-2RA, IL-3, LIF, MCP-1, MCP-3, M-CSF, SDF-1α, and TRAIL) attained 1000 pg/ml and even 1000-5000 pg/ml (G-CSF, HGF, IL-12, p40, IL-16, and MIF). The most abundant cytokines and growth factors in UC-MSC-conditioned media were GRO-α, IL-6, IL-8, and SCGF-ß (concentration range up to 5000-65,000 pg/ml) (page 536). A correlation between the "age" of cells (such number) and their secretory activity was shown (page 538). UC-MSC secretome in the form of conditioned medium is considered as a practically ready to use therapeutic product (pages 538-539).
Amable discloses a comparison of mesenchymal stem cells derived from BM, AT and WJ (Whartons Jelly) (page 2 column 1). The concentration of 49 different cytokines, growth factors and extracellular matrix-related proteins in the cell supernatant was quantified (page 3). WJ- MSC secrete a.o. pro-inflammatory cytokines (IL-8, IL-6) chemokines (MCP-1), angiogenic growth factors (angiopoietin-1), matrix metalloproteinases (MMP-1, -3) and growth factors (HGF, G-CSF). WJ MSC showed highest mitogenic profile (pages 3-9, Results and Discussion). The therapeutic application in regeneration is mentioned (page 1) and specifically that Wharton’s Jelly-derived MSCs provide a therapeutic effect that makes it a more angiogenic, neuroprotective and neurogenic option (page 2 column 1)..
Nishida discloses that exosomes derived from UC-MSC (umbilical cord-derived mesenchymal stem cells) and BM-MSC (bone marrow-derived mesenchymal stem cells) also express CD63 (column 21-22, para 88). These mesenchymal stem derived microparticles have activity that promotes the growth of corneal epithelial cells and protects corneal epithelium (column 22, para 89).
One of ordinary skill in the art would have been motivated to modify the therapeutic composition of Mathen to include the claimed additional components of conditioned medium (secretome) of cultured MSCs from umbilical cord tissue or Wharton’s Jelly tissue because Phan, Romanov, Amable and Nishida teach and suggest that these secreted factors are beneficial and desirable for use in a therapeutic composition. It is prima facie obvious to combine compositions which have been taught in the prior art to be useful for the same purpose in order to form another composition to be used for the very same purpose. The idea of combining them flows logically from their having been individually taught in the prior art (In re Kerkhoven) (see MPEP 2144.06).
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05).
The selection of specific concentrations clearly would have been a routine matter of optimization and experimentation on the part of the artisan of ordinary skill, said artisan recognizing that the therapeutic effect of the composition would have been affected by these concentrations. Purification of the condition medium to arrive at a composition that consists of only the most desirable components would have been motivated by Phan who teach and suggest that such purification is beneficial and desirable (page 10 para 135). One of ordinary skill in the art would have had a reasonable expectation of success because Mathen teach and suggest that the conditioned medium can be further concentrated by methods known to those in the art and formulated for therapeutic applications (page 4 para 72).
Regarding claims 14-15, these claims are product by process claims.
M.P.E.P. § 2113 reads, “Product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps.”
“Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted).
The structure implied by the process steps should be considered when assessing the patentability of product-by-process claims over the prior art, especially where the product can only be defined by the process steps by which the product is made, or where the manufacturing process steps would be expected to impart distinctive structural characteristics to the final product. See, e.g., In re Garnero, 412 F.2d 276, 279, 162 USPQ 221, 223 (CCPA 1979)
The use of 35 U.S.C. §§ 102 and 103 rejections for product-by-process claims has been approved by the courts. “[T]he lack of physical description in a product-by-process claim makes determination of the patentability of the claim more difficult, since in spite of the fact that the claim may recite only process limitations, it is the patentability of the product claimed and not of the recited process steps which must be established. We are therefore of the opinion that when the prior art discloses a product which reasonably appears to be either identical with or only slightly different than a product claimed in a product-by-process claim, a rejection based alternatively on either section 102 or section 103 of the statute is eminently fair and acceptable. 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).
Since claim 15 lists the same components as the composition of claim 1 and claim 1 is deemed to be rendered obvious by the teachings of Mathen, Phan, Romanov et al, Amable et al and Nishida et al as described above, claims 14-15 are also deemed to be rendered obvious as well.
Therefore, the combined teachings of Mathen, Phan, Romanov et al, Amable et al and Nishida et al render obvious Applicant’s invention as claimed.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Fong et al., “Human Wharton's Jelly Stem Cells and Its Conditioned Medium Enhance Healing of Excisional and Diabetic Wounds”, Journal of cellular Biochemistry, 2014, Vol. 115, pp.290–302.
(Fong disclose how the conditioned medium of stem cells from Wharton’s Jelly enhance healing of wounds.)
Pawitan et al., “Prospect of Stem Cell Conditioned Medium in Regenerative Medicine”, BioMed Research International, 2014, Volume 2014, Article ID 965849, pages 1-14.
(Pawitan disclose conditioned medium as a manufactured product)
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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LAURA J. SCHUBERG
Primary Examiner
Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631
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