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 response to the restriction requirement mailed on 9/16/2025 was acknowledged. Applicant stated that claims 16-20 were erroneously presented as “composition” claims, and they should be directed to the method claims. Applicant has amended claims 16-20 as method claims dependent on claim 1.
Based on the applicant’s argument, the restriction requirement was moot as there were no distinct groups of inventions presented in the claims.
Claims 1-20 have been considered on the merits.
Priority
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/319,878, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Claim 1 discloses “perinatal tissue” as a source of the claimed regenerative source. However, the prior filed provisional application fails to provide support to the subject matter directed to the “perinatal tissue” as the scope of perinatal tissue is broader than the subject matter disclosed in the ‘878 application which only discloses “subepithelial area of the umbilical cord”, i.e. Wharton’s jelly, or placenta perivascular tissue. Thus, the priority claim to the ‘878 application is not granted and the earliest filing date of the instant application is determined as 3/15/2023.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
The specification is objected to as failing to provide proper antecedent basis for the claimed subject matter. See 37 CFR 1.75(d)(1) and MPEP § 608.01(o). Correction of the following is required: claim 1 discloses the term “perinatal tissue” for the source of the claimed regenerative cells. Other than claim 1, there is no disclosure of this term in the instant specification. Thus, there is no antecedent basis of the claimed “perinatal tissue” in the instant specification. While umbilical cord is considered as a perinatal tissue, however, the scope of the “perinatal” tissue appears to be broader than umbilical cord, and the instant specification does not provide sufficient support for the entire scope of “perinatal tissue”.
Claim Objections
Claims 4, 8 and 10 are objected to because of the following informalities:
Claim 4 discloses “VEGF-D 6Ckine”, “VEGFR1Adiponectin”, “XEDARActivin A”. They appear to be typographical errors. There should be a comma between these terms. In addition, the listed species of claim 4 contains duplicates: e.g. HGF, uPAR, VEGF, etc. Applicant is advised to carefully review the names of the listed species.
Claim 8 discloses the term “derivates” in line 1. It appears a typographical error for “derivatives”.
Claim 10 discloses “TLR. 1.” It appears a typographical error of “TLR-1”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 7 and 9 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 7 discloses the limitation of “derivatives of said regenerative cell”. The scope of the term “derivatives” is extensive to encompass not only the derivatives disclosed in claim 8 but also any cells derived from the regenerative cells including genetically modified cell thereof; or differentiated cells thereof, etc.
Applicant generically claims a method employing “derivatives” of the regenerative cells of claim 1, however the specification does not contain an adequate description for the entire scope of this limitation and thus the claims. The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
Claim 9 discloses that the regenerative cells are treated with an activator of an immune receptor. The scope of “an activator of an immune receptor” is extremely broad as the “immune receptor” is not particularly defined and thus, it includes any chemokine, cytokine or pathogen receptors including pattern recognition receptors including TLRs or NLRs, complement receptors, Fc receptors, B cell receptors, T cell receptors, cytokine receptors. The instant specification discloses that the immune receptors are TLRs and the activator thereof.
The specification fails to provide sufficient written description to support that the inventors had possession on the entire scope of the claimed genus of an activator of an immune receptor as it only discloses TLRs and their activators.
M.P.E.P. §2163 recites, “The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus…when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus.”
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 1-20 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 1 discloses that the regenerative cells are derived from the subepithelial area of the umbilical cord and/or perinatal tissue. It is not clear if the subepithelial area is limited to the umbilical cord or it also refers to the perinatal tissue. In other words, it is not clear if the regenerative cells are derived from 1) subepithelial area of umbilical cord and/or 2) perinatal tissue; or from subepithelial area of 1) umbilical cord and/or 2) perinatal tissue. Under the interpretation of “subepithelial area of perinatal tissue”, it is vague what subject matter this limitation intends to point out. Clarification is required.
For search purpose, the limitation is interpreted as the regenerative cells are derived from 1) subepithelial area of the umbilical cord, or 2) perinatal tissue.
Claim 3 discloses the term “reduction suppression”. It is not clear what this term intends to point out. Is it meant to be “reduction” and/or “suppression” or “suppression” is “reduced”?
Claim 4 discloses species of growth factors. Some of the listed species does not appear to be growth factors. For example, the species includes M-CSF R, NGF R, SCF R, VEGFR2, VEGFR3, GIRT, IL-1 R4, IL-1 RI, IL-10 Rbeta, etc. These appear to be receptors for the corresponding growth factors, not the growth factors per se. It is not clear how these species belong to the claimed growth factors. There are other molecules not typically known as a growth factor, for example, I-309, IL-1 ra, CD40 ligand, Fas Ligand, Axl, syndecan-1, Fcg RIIB/C, etc. Clarification is required.
Claim 4 disclose “Light” in line 11. It is not clear what the subject matter the term intends to point out. There is no known growth factor named as “Light” in the art. Clarification is required.
Claim 7 discloses that the derivatives of the regenerative cell of claim 1 are utilized for radioprotection. As claim 1 does not disclose “radioprotection”, this limitation appears to direct to an additional purpose of the derivatives of the regenerative cell. The term “radioprotection” is not particularly defined for its scope and thus, under the broadest reasonable interpretation, the scope of “radioprotection” could include preventative means against any radiation exposure or treatment to radiation exposure as intended in claim 1. It is not clear what the metes and bounds of the “radioprotection” are. Clarification is required. For search purpose, the wherein clause of claim 7 is interpreted as an optional clause because the derivatives of the regenerative cell is not required by the claimed method of treating radiation exposure.
Claim 10 discloses the term “TLR. 1.” It is not clear what subject matter this term intends to point out. For search purpose, the limitation is interpreted as TLR-1.
Claim 14 discloses the term “said cell population” in line 1. There is no antecedent basis for this term as claim 1 does not disclose any “population”.
Claim 17 discloses the term “said regenerative adjuvant” in line 1. There is no antecedent basis for this term as claim 1 does not disclose any “regenerative adjuvant”.
Claim 19 discloses that the anti-inflammatory cytokine is VEGF. It is not clear how VEGF is considered as anti-inflammatory cytokine as it is well known in the art that VEGF is pro-inflammatory cytokine. Clarification is required.
Claim 20 discloses the term “said composition” in line 1. There is no antecedent basis for the “composition” as claim 1 does not disclose any “composition”. Thus, the claim is indefinite as it is not clear which composition it refers to.
Claim 4 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of growth factors in claim 4 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: the species listed in claim 4 are just a list of any known molecules that have been reduced by radiation exposure. As discussed above, some of the species are not even considered as growth factors, e.g. receptors or ligand, etc., and there is no structural similarity between the listed growth factors.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
It is also noted that the species of claim 4 are not required for the claimed method to be carried out, rather the species of claimed growth factors and other molecules are those with reduced expression as a result of the radiation exposure, and they do not provide any weight in determining patentability of the claimed method. Thus, applicant is suggested to either cancel claim 4 or amend to only include growth factors within the Markush group.
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 16 and 19 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.
Claim 16 discloses that the cells of claim 1 are obtained from placenta perivascular tissue. Claim 1 discloses that the regenerative cells are obtained from the subepithelial area of the umbilical cord and/or perinatal tissue. There is no indication that placenta perivascular tissue is within the scope of the subepithelial area of the umbilical cord and/or perinatal tissue. Thus, claim 16 does not further limit the limitation of claim 1.
Claim 19 discloses that the anti-inflammatory cytokine is VEGF, and claim 19 is dependent on claim 18. Claim 18 discloses that the anti-inflammatory cytokine is selected from the group which does not include VEGF. Thus, claim 19 does not further limit claim 18.
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 § 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.
Claim(s) 1-8, 11-14 and 20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bandekar et al. (2020, Am. J. Transplant.) as evidenced by Bandekar2021 (2021, Current Stem Cell Reports)
Regarding claim 1, Bandekar et al. teach a method of treating acute radiation syndrome in mice exposed to ionizing radiation (IR) by administering Wharton’s jelly mesenchymal stem cell (WJ-MSCs) from human umbilical cord (Abstract; Materials and Methods, p.2045). Bandekar et al. transplanted WJ-MSCs at 1x106 intravenously (p.2045) to produce enhanced radioprotection (p.2046, 3.2. WJ-MSCs protected mice against lethal dose of IR), and this teaching would meet the therapeutic dose of regenerative cells. The Wharton’s jelly is considered to meet the subepithelial area of the umbilical cord or perinatal tissue. This is because the it is known in the art that Wharton’s jelly is a layer of gelatinous tissue that lies under the epithelial lining of the umbilical cord, and thus, Wharton’s jelly is considered as the subepithelial area of the umbilical cord or perinatal tissue. It is also noted that the instant specification discloses that the regenerative cell is obtained from Wharton’s jelly (p.16, claim 159).
Regarding the wherein clause of claim 2 directed to the radiation exposure being associated with damage to the hematopoietic system, the limitation does not require any active step to be carried out for the method of claim 1, rather it is directed to the characteristics of the radiation exposure. Thus, the limitation does not provide any patentable weight in determining patentability of the claimed method. Nevertheless, it is known that radiation exposure would damage the hematopoietic system of the subject as Bandekar et al. teach that IR-induced damage includes the hematopoietic and gastrointestinal system (see Abstract). This teaching would also meet the limitation of claim 5.
Regarding claims 3-4 directed to the damage to the hematopoietic system being reduction/suppression of growth factors produced by bone marrow stromal cell, and the types of growth factors being reduced, the wherein clause does not require any active step to be carried out for the method of claim 1, rather it is directed to the characteristics of the hematopoietic damage and/or the results of the radiation exposure. As Bandekar et al. teach that the IR induces hematopoietic damage, it is expected that the IR would produce the same hematopoietic damage and the reduction of growth factors produced by bone marrow stromal cells as claimed.
Regarding claim 6 directed to the radiation exposure being associated with damage to the respiratory system, the wherein clause of claim 6 is also considered as a result of the radiation exposure. Thus, the limitation does not require any active step to be carried out for the method of claim 1, and thus, do not limit the claimed method. Furthermore, it is known in the art that radiation exposure to whole body induces multi-organ toxicity including hematopoietic, gastro-intestinal and lung damage according to Bandekar2021.
Regarding claims 7-8 directed to the derivatives of the regenerative cell being utilized for radioprotection, and the derivatives include exosomes, Bandekar et al. do not particularly teach the limitation. However, it is considered that the exosomes of the WJ-MSCs of Bandekar et al. would inherently contain exosomes within the cells and thus, when the WJ-MSCs of Bandekar et al. are administered to treat a radiation exposure, it would inherently contain derivatives of the cells, i.e. exosomes.
Regarding claim 20, the “composition” is not disclosed in claim 1 and thus, it is interpreted as the regenerative cells of claim 1. The wherein clause of claim 20 is directed to the characteristics of the regenerative cells. As the WJ-MSCs of Bandekar et al. are considered identical to the claimed regenerative cells, the characteristic of the WJ-MSCs of Bandekar et al. would inherently identical to the claimed cells.
Thus, the reference anticipates the claimed invention.
Claim(s) 1-8, 11-14 and 20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Patel (US 9,803,176) as evidenced by Lopez et al. (2011, Reports of Practical Oncology and Radiotherapy)
Patel teaches a method of treating a medical condition including acute radiation syndrome by administering the isolated stem cells from a subepithelial layer of a mammalian umbilical cord (isolated SL cells) (col.2, 2nd para. and last para.; col. 12, line 64 thru col. 13, line 22; Example 12-13, col.18). Example 12 discloses that the mice were received lethal irradiation and thus, this teaching would meet the radiation exposure.
Regarding the wherein clause of claim 2 directed to the radiation exposure being associated with damage to the hematopoietic system, the limitation does not require any active step to be carried out for the method of claim 1, rather it is directed to the characteristics of the radiation exposure. Thus, the limitation does not provide any patentable weight in determining patentability of the claimed method. The acute radiation syndrome taught by Patel is considered to cause the identical damage to the hematopoietic system as claimed as Lopez et al. teach that the acute changes seen within the first 2 months following exposure include damages to skin, CNS, lung, GI tract and hematopoietic tissues (p.141, 6. Phases of acute radiation injury). Thus, the acute radiation syndrome of Patel would inherently cause the damage to the hematopoietic system (claim 2), the gastrointestinal system (claim 5) and/or the respiratory system (claim 6).
Regarding claims 3-4 directed to the damage to the hematopoietic system being reduction/suppression of growth factors produced by bone marrow stromal cell, and the types of growth factors being reduced, the wherein clause does not require any active step to be carried out for the method of claim 1, rather it is directed to the characteristics of the hematopoietic damage and/or the results of the radiation exposure. As the acute radiation syndrome taught by Patel would inherently include hematopoietic system damage, it is expected that the reduction suppression of growth factors produced by bone marrow stromal cells as claimed would be inherently produced in the subject having acute radiation syndrome of Patel.
Regarding claim 7 directed to the derivatives of the regenerative cell being utilized for radioprotection, Patel teaches that differentiated SL cells can be delivered to the subject to treat the medical condition (col. 12, lines 5-7). The differentiated cells from SL cells would meet the derivatives of the regenerative cell.
Regarding claim 8 directed to the derivatives being exosomes, it is submitted that the SL cells inherently contain exosomes in the cells as they are secreted from the SL cells when cultured. Thus, the method of administering the SL cells for treating acute radiation syndrome taught by Patel would meet the limitation.
Regarding claim 11 directed to the cells express GM-CSF receptor, Patel does not teach the limitation. However, the SL cells of Patel are identical to the regenerative cells obtained from subepithelial area of the umbilical cord, and thus, the property of the SL cells of Patel is inherently the same as the claimed cells.
Regarding claim 12 directed to the cells express surface vimentin and a marker as listed including CD29 or CD90, Patel does not teach the limitation. However, the SL cells of Patel are identical to the regenerative cells obtained from subepithelial area of the umbilical cord, and thus, the property of the SL cells of Patel is inherently the same as the claimed cells.
Regarding claim 13 directed to the ability of the regenerative cells, directed to the cells express GM-CSF receptor, Patel does not teach the limitation. As the SL cells of Patel are identical to the regenerative cells obtained from subepithelial area of the umbilical cord, and thus, the property of the SL cells of Patel is inherently the same as the claimed cells.
Regarding claim 14 directed to the cell population expresses IL-6 receptor and CD73, Patel teaches the expression of CD73 (Abstract). However, it does not teach the IL-6R. However, the SL cells of Patel are identical to the regenerative cells obtained from subepithelial area of the umbilical cord, and thus, the property of the SL cells of Patel is inherently the same as the claimed cells.
Regarding claim 20, the “composition” is not disclosed in claim 1 and thus, it is interpreted as the regenerative cells of claim 1. The wherein clause of claim 20 is directed to the characteristics of the regenerative cells. As the WJ-MSCs of Bandekar et al. are considered identical to the claimed regenerative cells, the characteristic of the WJ-MSCs of Bandekar et al. would inherently identical to the claimed cells.
Thus, the reference anticipates the claimed invention.
Claim(s) 1 and 16 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Aberman et al. (US2017/0368106A1) as evidenced by Park et al. (2011, Stem Cells & Development) and Deus et al. (2020, Acta Biomaterialia)
Regarding claims 1 and 16 directed to a method of treating radiation exposure by administering a regenerative cell obtained from the subepithelial area of the perinatal tissue, Aberman et al. teach a method of treating radiation exposure by using adherent stromal cells (Abstract; paras. 8, 79, 84, 240), and the stromal cells are originated from placenta (para. 84-85). The placental adherent stromal cells of Aberman et al. are derived from a fetal portion of the placenta, e.g. chorionic villi (para. 181). The chorionic villi is considered as a placenta perivascular tissue as Park et al. teach that the perivascular mesenchymal progenitors of placenta are derived from chorionic villi (Abstract; Materials and Methods). The chorionic villi is considered as a perinatal tissue as the chorion is a fetal tissue of the placenta and Deus et al. teach that the perinatal tissues include chorionic villus (see Fig. 1). Aberman et al. teach a step of administering to the subject a therapeutically effective amount of the cells to treat the radiation exposure (para. 227 and 244).
Thus, the reference anticipates the claimed invention.
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.
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.
Claim(s) 9-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bandekar et al. (supra) as applied to claim 1 as above, in view of Ichim et al. (US2017/0296588A1) and Noronha et al. (2019, Stem Cell Research & Therapy).
Bandekar et al. anticipate the subject matter of claims 1-8, 11-14 and 20 as discussed above and thus, render them obvious.
Regarding claims 9-10 directed to the cells being treated with an activator of an immune receptor, and the receptor being TLR-1, Bandekar et al. do not teach the limitation.
Ichim et al. teach that the placenta derived mesenchymal stem cells can be utilized for a therapeutic purpose in regenerative, immune modulatory and angiogenic applications (Abstract). Ichim et al. teach that the mesenchymal stem cells are stimulated by an inflammatory signal and the inflammatory signal includes an activator of a toll-like receptor (TLR) including TLR-1, and the activator of TLR-1 is Pam3CSK4 (paras. 121-124).
It would have been obvious to a person skilled in the art to treat the WJ-MSCs of Bandekar et al. with Pam3CSK4, an activator of TLR-1, in order to stimulate the cells for the method of treating a subject exposed by radiation. A person of ordinary skilled in the art would have been motivated to do so because Ichim et al. teach that the stimulation of MSCs with an inflammatory signal would prime the MSCs enhance their anti-inflammatory properties according to Noronha et al. (p.2, MSC priming with cytokines; p.6, Other combinatory strategies of pro-inflammatory cytokines). As Ichim et al. teach that a TLR-1 activator is a pro-inflammatory signal, one skilled in the art would expect that the treating of MSCs with an activator of TLR-1 taught by Ichim et al. would prime the WJ-MSCs of Bandekar et al. anti-inflammatory for the method of treating a radiation exposure with a reasonable expectation of success.
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.
Claim(s) 9-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Patel (supra) as applied to claim 1 as above, in view of Ichim et al. (supra) and Noronha et al. (supra).
Patel anticipates the subject matter of claims 1-8, 11-14 and 20 as discussed above and thus, render them obvious.
Regarding claims 9-10 directed to the cells being treated with an activator of an immune receptor, and the receptor being TLR-1, Patel does not teach the limitation.
Ichim et al. teach that the placenta derived mesenchymal stem cells can be utilized for a therapeutic purpose in regenerative, immune modulatory and angiogenic applications (Abstract). Ichim et al. teach that the mesenchymal stem cells are stimulated by an inflammatory signal and the inflammatory signal includes an activator of a toll-like receptor (TLR) including TLR-1, and the activator of TLR-1 is Pam3CSK4 (paras. 121-124).
It would have been obvious to a person skilled in the art to treat the SL cells of Patel with Pam3CSK4, an activator of TLR-1, in order to stimulate the cells for the method of treating acute radiation syndrome. A person of ordinary skilled in the art would have been motivated to do so because Ichim et al. teach that the stimulation of MSCs with an inflammatory signal would prime the MSCs enhance their anti-inflammatory properties according to Noronha et al. (p.2, MSC priming with cytokines; p.6, Other combinatory strategies of pro-inflammatory cytokines). As Ichim et al. teach that a TLR-1 activator is a pro-inflammatory signal, one skilled in the art would expect that the treating of MSCs with an activator of TLR-1 taught by Ichim et al. would prime the SL cells of Patel to possess anti-inflammatory properties for the method of treating acute radiation syndrome with a reasonable expectation of success.
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.
Claim(s) 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bandekar et al. (supra) as applied to claim 1 as above, in view of Cheema et al. (2021, Animal Microbiome).
Bandekar et al. anticipate the subject matter of claims 1-8, 11-14 and 20 as discussed above and thus, render them obvious.
Regarding claim 15 directed to the patient being also treated in a manner to alter the gut microbiome, Bandekar et al. do not teach the limitation.
Cheema et al. teach that the treatment of irradiated mice with BIO300 restored normal gut microbiota and alleviated the inflammatory metabolic phenotype in the irradiated mice (Abstract; p.6). BIO300 is synthetic genistein formulated as a nanoparticle suspension, and genistein is a naturally occurring isoflavone found in soybean, and it has been shown to be an effective radiation countermeasure with radioprotective efficacy (p.2, 2nd col.).
It would have been obvious to a person skilled in the art to use the method of treating a subject exposed to radiation with BIO300 taught by Cheema et al. along with the WJ-MSCs of Bandekar et al. A person of ordinary skilled in the art would have been motivated to do so because BIO300 is known to be effective in treating radiation exposure according to Cheema et al. As Cheema et al. teach that BIO300 restores normal gut microbiome, the use of BIO300 would meet the limitation of “in a manner to alter the gut microbiome” as claimed.
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.
Claim(s) 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Patel (supra) as applied to claim 1 as above, in view of Cheema et al. (supra).
Patel anticipates the subject matter of claims 1-8, 11-14 and 20 as discussed above and thus, render them obvious.
Regarding claim 15 directed to the patient being also treated in a manner to alter the gut microbiome, Patel does not teach the limitation.
Cheema et al. teach that the treatment of irradiated mice with BIO300 restored normal gut microbiota and alleviated the inflammatory metabolic phenotype in the irradiated mice (Abstract; p.6). BIO300 is synthetic genistein formulated as a nanoparticle suspension, and genistein is a naturally occurring isoflavone found in soybean, and it has been shown to be an effective radiation countermeasure with radioprotective efficacy (p.2, 2nd col.).
It would have been obvious to a person skilled in the art to use the method of treating a subject exposed to radiation with BIO300 taught by Cheema et al. along with the SL cells of Patel in treating acute radiation syndrome. A person of ordinary skilled in the art would have been motivated to do so because BIO300 is known to be effective in treating radiation exposure according to Cheema et al. As Cheema et al. teach that BIO300 restores normal gut microbiome, the use of BIO300 would meet the limitation of “in a manner to alter the gut microbiome” as claimed.
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.
Claim(s) 17-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bandekar et al. (supra) as applied to claim 1 as above, in view of Van der Meeren et al. (1999, Cytokine)
Regarding claims 17-18 directed to the regenerative adjuvant being an anti-inflammatory cytokine including IL-4 and IL-10, Bandekar et al. do not teach the limitation.
Van der Meeren et al. teach that cytokines IL-4 and IL-10 regulate radiation-induced IL-6 and IL-8 production, and IL-4 and IL-10 can be used for cytokine-mediated intervention and/or therapy of radiation damage (Abstract).
It would have been obvious to a person skilled in the art to use IL-4 and/or IL-10 along with the method of Bandekar et al. in treating a radiation exposure with a reasonable expectation of success. A person of ordinary skilled in the art would have been motivated to do so because IL-4 and IL-10 were taught to be used for treating radiation damage according to Van der Meeren et al. and one skilled in the art would recognize the benefit of these cytokines for the same purpose of the method treating a radiation exposure of Bandekar et al.
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.
Claim(s) 17-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Patel (supra) as applied to claim 1 as above, in view of Van der Meeren et al. (supra)
Regarding claims 17-18 directed to the regenerative adjuvant being an anti-inflammatory cytokine including IL-4 and IL-10, Patel does not teach the limitation.
Van der Meeren et al. teach that cytokines IL-4 and IL-10 regulate radiation-induced IL-6 and IL-8 production, and IL-4 and IL-10 can be used for cytokine-mediated intervention and/or therapy of radiation damage (Abstract).
It would have been obvious to a person skilled in the art to use IL-4 and/or IL-10 along with the method of Patel in treating acute radiation syndrome with a reasonable expectation of success. A person of ordinary skilled in the art would have been motivated to do so because IL-4 and IL-10 were taught to be used for treating radiation damage according to Van der Meeren et al. and one skilled in the art would recognize the benefit of these cytokines for the same purpose of the method treating acute radiation syndrome of Patel.
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.
Claim(s) 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bandekar et al. (supra) as applied to claim 1 as above, in view of Chen et al. (2017, J. Rad. Res.)
Regarding claim 19 directed to the anti-inflammatory cytokine being VEGF, Bandekar et al. do not teach the limitation.
Chen et al. teach that in vivo study showed that VEGF treatment significantly promoted the migration of megakaryocytes into the vascular niche and accelerated platelet recovery in irradiated mice (Abstract).
It would have been obvious to a person skilled in the art to use VEGF along with the method taught by Bandekar et al. as the effect of VEGF is beneficial for recovery of endothelial cells after radiation exposure. A person of ordinary skilled in the art would have been motivated to do so because a person skilled in the art would recognize the benefit of VEGF in treating radiation exposure, and thus, combine VEGF with the regenerative WJ-MSCs of Bandekar et al. for the same purpose of treating radiation exposure.
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.
Claim(s) 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Patel (supra) as applied to claim 1 as above, in view of Chen et al. (supra)
Regarding claim 19 directed to the anti-inflammatory cytokine being VEGF, Patel does not teach the limitation.
Chen et al. teach that in vivo study showed that VEGF treatment significantly promoted the migration of megakaryocytes into the vascular niche and accelerated platelet recovery in irradiated mice (Abstract).
It would have been obvious to a person skilled in the art to use VEGF along with the method taught by Patel as the effect of VEGF is beneficial for recovery of endothelial cells after radiation exposure. A person of ordinary skilled in the art would have been motivated to do so because a person skilled in the art would recognize the benefit of VEGF in treating radiation exposure, and thus, combine VEGF with the regenerative SL-MSCs of Patel for the same purpose of treating radiation exposure.
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.
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/TAEYOON KIM/ Primary Examiner, Art Unit 1631