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 .
Notice of Pre-AIA or AIA Status
DETAILED ACTION
Status of the Claims
Claims 1-20 are pending. Claims 3-6 and 18-20 are withdrawn. Claims 1-2 and 7-17 are under examination.
Priority
This application is a national stage entry of PCT/KR2021/018354 filed on 12/06/2021, which claims priority from KR10-2020-0168689 filed on 12/4/2020.
Information Disclosure Statement
The information disclosure statements filed on 6/2/2023 and 7/5/2023 have been considered by the examiner.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-2 and 7-17) and species a) umbilical cord blood stem cells and b) IL-10 in the reply filed on 12/15/2025 is acknowledged. Claims 3-6 and 18-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 12/15/2025.
Claim Objections
Claim 1 is objected to for “an concentration” which needs to be “a concentration”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 7-17 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 7 recites the limitation "separating umbilical cord blood stem cells, their culture conditioned medium, and/or their exosomes obtained from step (i)" in where the claim provides for two step (i) items with the first being “(i) treating umbilical cord blood stem cells during culture” and the second being “(i) with lipoteichoic acid (LTA)…”, then there is another option (ii) that appears to be contained within the context of the initial step (i). (also note that there are two option (i)’s and two option (ii)’s in the claim.) It is unclear which option (i) is being referred to when considering the limitation in step (ii) of the claim and if applicant means to perform or not perform this step if the cells are treated with lipopolysaccharide and lipoteichoic acid. There is insufficient antecedent basis for this limitation in the claim. This issue may be corrected by having the main steps of “treating…” and “optionally, separating” provided as (a) and (b) rather than (i) and (ii), so there is a noted difference in what is being referred to. Dependent claim would have to be changed accordingly.
Claims 8-17 are rejected for being dependent on an indefinite claim without repairing the issue of indefiniteness.
Claim 8 recites the limitation "(i) involves treating stem cells during cultivation with both lipopolysaccharide and lipoteichoic acid" in dependence to claim 7, which provides for “(ii) with lipopolysaccharide (LPS) and lipoteichoic acid (LTA)..” and “(i) treating umbilical cord blood stem cells during culture (i) with lipoteichoic acid (LTA) or (ii) with lipopolysaccharide and lipoteichoic acid (LTA)…”. It is unclear if applicant is trying to limit the step “(i) treating..” to what would be the step (ii) option or if applicant is trying to redefine the other step “(i) with lipoteichoic acid” limitation as “lipopolysaccharide and lipoteichoic acid”. As noted above, this issue may be corrected by having the main steps in claim 7 of “treating…” and “optionally, separating” provided as (a) and (b) rather than (i) and (ii), so there is a noted difference in what is being referred to. Then claim 8 may be amended to say “step (a) involves treating the stem cells during cultivation (ii) with both lipopolysaccharide (LPS) and lipoteichoic acid (LTA).”
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 10-12, and 16 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. These claims provide for treatment with lipopolysaccharide and/or lipoteichoic acid where claim 7, on which they depend requires treatment with lipoteichoic acid and lipopolysaccharide as one of the options. As these claims (10-12 and 16) would be toward treatment with lipopolysaccharide as a separate option, they extend the treatment that was previously recited in claim 7 to being lipopolysaccharide alone. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. Applicant may recite “lipoteichoic acid or a combination of lipoteichoic acid and lipopolysaccharide” in claims 10-12 and 16 instead.
Claim 17 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 17 defines the stem cells as umbilical cord blood stem cells, but these are already the cells used in claim 7. There is no further limitation provided. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 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.
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 1-2 and 7-17 are rejected under 35 U.S.C. 103 as being unpatentable over Gonzalez US 20170166869 and Ti et al (Journal of Translational Medicine, 2015, volume 13, pages 1-14).
Gonzalez teaches mesenchymal stem cells augmented with immune modulatory activity where an agent or agents induces a stress response in the mesenchymal stem cells (claims 1 and 9 of Gonzalez and paragraph 6). Gonzalez teaches agents including lipoteichoic acid (LTA) from gram positive bacteria and lipopolysaccharide (LPS) (claim 10 of Gonzalez). Gonzalez teaches umbilical cord mesenchymal stem cells (claim 11 of Gonzalez). Gonzalez teaches human umbilical cords to obtain cells (paragraph 23). In example 1, Gonzalez provides for stimulating a stress response by culturing for 48 hours in interferon gamma (another agent) in DMEM media (paragraph 23). Gonzalez teaches serum free culture mediums known in the art (paragraph 20). Gonzalez teaches “amount of cells, conditioned media or exosomes that, when administered to a mammal for treating a chronic wound, or angiogenic insufficiency is sufficient to effect such treatment” (paragraph 10). Thus, each of the components including the exosomes is seen as therapeutic in Gonzalez. Gonzalez allows for purifying exosomes from the MSC’s (paragraph 18). Gonzalez teaches “the invention provides means to “prime” MSC in vitro before administration, for augmentation of homing, immune modulatory, and therapeutic activity” (paragraph 6). Gonzalez teaches regeneration of blood vessels (paragraph 8). Gonzalez teaches “Specific embodiments of the invention include stimulation of angiogenic and immune modulatory properties by preconditioning with interferon-gamma, as well as other physiologically-relevant stressors” (abstract). Gonzalez teaches chronic wound treatment (paragraphs 9-11).
Gonzalez does not examine the increase in IL-10 or TGFbeta-1 in the exosomes during the culture and uses a different stressor agent even though it allows for both LTA and LPS as options for the stressor agent.
Ti teaches LPS preconditioned mesenchymal stromal cells have a potential for wound healing and for chronic inflammation therapies (abstract and conclusions). Ti teaches using human umbilical cord MSCs and “After the medium was aspirated, the cells were rinsed three times with PBS and treated with LPS (100 ng/ml in serum-free medium, Sigma, USA) or serum-free medium alone as a negative control and then incubated for 2 days prior to supernatant collection” (page 3, first column). Ti teaches using LPS pre-treatment enhanced exosome secretion (figure 2). Ti teaches LPS pre-treatment also produced more anti-inflammatory cytokines (IL-10, TGF beta) (page 6, first column and figure 3). Ti shows treating a wound with the exosomes (figure 7). Ti teaches exosome extraction by filtering and centrifugation (page 3, first column). The LPS in Ti is used to pre-treat the cells to stimulate the cells, but would not become internalized into the exosome itself.
One of ordinary skill in the art before the time of filing would have reasonably expected that cells treated with the stressor agents including LTA with or without LPS would be capable of inducing more exosome secretion as well as more IL-10 and TGF beta in the combination of Gonzalez and Ti since Gonzalez recognizes LTA and LPS as stressor agents to pre-treat cells as well as separating exosomes from the cell culture, while Ti provides that LPS (another stressor found in Gonzalez) induces IL-10, TGF beta and more exosome secretion. Both references recognize the ability of stressor agent (LPS, LTA) treatment to be useful for wound therapy development by using them to pre-treat stem cells. Therefore, there was a reasonable expectation of success through the combination of the prior art of pre-treating umbilical cord blood stem cells with LPS and/or LTA during cell culture and obtaining the exosomes or an anti-inflammatory and/or regenerative composition that will be useful for wound treatment. In regards to claim 14, as the teachings of the prior art allow for an anti-inflammatory and healing/regenerative composition (e.g. exosomes), it will allow for such reduction of pro-inflammatory factor and increases in TGFbeta-1 and/or IL-10 when applied to cells (these are anti-inflammatory effects). Also, note that claim 14 is toward the result of a use of the product made in the process of making and not a limitation to the process of making itself.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARK V STEVENS whose telephone number is (571)270-7080. The examiner can normally be reached M-F 9:00 am to 6:00 pm EST.
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/MARK V STEVENS/Primary Examiner, Art Unit 1613