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 .
Claims 1-32 have been canceled. Claims 33-45 have been added and are examined on the merits.
Information Disclosure Statement
The IDS filed on 12/1/2023 is “X-ed” out because it is a duplicate of the IDS filed 11/22/2023.
Priority
Applicant has not provided translations for the foreign applications JP2021-034016 and JP2021-034018. Thus, the effective filing date for purpose of prior art determination is considered to be 3/3/2022.
Claim Rejections - 35 USC § 112
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 33-45 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.
(A)The recitation of “1.20 times or higher as compared with a control fibroblast”. In claims 33, 39 and 41 render the claims indefinite because neither the claims nor the specification provide a limiting definition of what constitutes a “control fibroblast” in terms of species and tissue origin.
(B)Regarding claim 35, it is unclear if applicant intends that “treating fibrosis” is the result of administration or transplantation of the pharmaceutical composition, or if applicant intends the administration of a separate anti-fibrotic agent or treatment.
(C)The recitation of “the cell population” in claim 39 lacks specific antecedent basis within the claim.
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.
Claim 33-39, 41, 42, 44 and 45 are rejected under 35 U.S.C. 103 as being unpatentable over as Iwamiya et al (WO2020/045547, reference of the IDS filed 11/22/23) as evidenced by Iwamiya et al (US2021/0254009, reference of the IDS filed 11/22/23) in view of Iwamiya et al (PLoS One, 2020, Vol. 15, No. 9, article 0237810, reference of the IDS reference of the IDS filed 11/22/23).
Claim 33 is drawn to a method for ameliorating a disease condition in a subject comprising administering or transplanting a pharmaceutical composition comprising a fibroblast highly expressing ADM and/or HHEX to the subject, wherein the gene expression level of ADM and/or HHEX in the fibroblast is 1.2o times or higher as compared to a control fibroblast, wherein the disease or condition is reduced lymphangiogenesis ability. Claim 34 specifies that the fibroblast is an adult-derived fibroblast. Claim 35 requires treating fibrosis. Claim 36 specifies that the pharmaceutical composition is injectable. Claim 37 specifies that the pharmaceutical composition is a planar or three-dimensional cellular tissue. Claim 38 requires that the fibroblast is a cardiac fibroblast.
Claim 39 is drawn in part to a method for ameliorating a condition of reduced lymphangiogenesis ability in a subject, the method comprising administering or transplanting into the subject (a)a fibroblast highly expressing ADM or (b) a cell population comprising the fibroblast highly expressing ADM, wherein gene expression level of ADM of the fibroblast highly expressing ADM is 1.20 times higher than that of a control fibroblast.
Claim 41 requires that the fibroblast highly expressing ADM highly expresses VEGF-C wherein the gene expression level of VEGF-C in the fibroblast highly expressing ADM is 1.20 times or higher as compared with a control fibroblast. Claim 42 specifies that the fibroblast highly expressing ADM is CD106+. Claim 44 specifies that the pharmaceutical composition is injectable. Claim 45 specifies that the pharmaceutical composition is a planar or three-dimensional cellular tissue.
Iwamiya et al (‘547) teach methods of producing CD106-positive and CD90-positive fibroblasts and pharmaceutical compositions comprising the fibroblasts for treatment of heart diseases (paragraph [0002]), wherein the heart disease includes heart failure, ischemic heart diseases, myocardial infarction, cardiomyopathy, myocarditis, hypertrophic cardiomyopathy (paragraph [0089]). Iwamiya et al teach that the culture of the fibroblasts in TNFα and Il-4 leads to an increase in the number of CD106+ and CD90+ fibroblasts paragraph [0008]). Iwamiya et al teach that the pharmaceutical composition of the invention comprising CD106+ and CD90+ fibroblasts can be used to improve cardiac function, and in the prevention of fibrosis progression in cardiac tissues,(paragraph [0089]) which meets the limitation of claim 35 as fibrosis is treated as a result of administration of the pharmaceutical composition. Iwamiya et al teach that the pharmaceutical composition is used as an injectable composition (paragraphs [0092-0095]) which meets the limitation in claim 36 and 44. Iwamiya et al teach that the fibroblast population may be used as a planar or three-dimensional tissue (paragraphs [0097-0098]) which meets the same limitation in claims 37 and 45. Iwamiya et al teach that the fibroblast is an adult-derived cardiac fibroblast cultured in TNFα and Il-4 (paragraphs [0023-0024]).
Iwamiya et al (‘547) teach the administration of the fibroblast for the treatment of heart failure and myocardial infarction. Iwamiya et al do not teach the administration of the fibroblasts to a subject for amelioration of a condition of reduced lymphangiogenesis ability. Iwamiya et al do not specifically teach that the CD106+ and CD90+ fibroblasts produced by culture with TNFα and Il-4 highly express adrenomedullin and/or HHEX.
Iwamiya et al (PLoS One) teach that human cardiac fibroblasts expressing VCAM1 improve heart function in postinfarct heart failure rat models by stimulating lymphangiogenesis (title). VCAM1 is otherwise known as CD106. Iwamiya et al (PLoS One) teach that VCAM1 expressing cardiac fibroblasts when injected into the infarct restore the properties of ventricular walls by mobilizing lymphatic endothelial cell into the infarct (abstract)
It would have been prima facie obvious at the time prior to the effective filing date to administer the fibroblasts of Iwamiya et al (‘547) to subjects with heart failure after myocardial infarction to treat reduced lymphangiogenesis in the subjects by stimulating lymphangiogeneisi. One of skill in the art would have been motivated to do so by the teachings of Iwamiya et al (PLoS One) that VCAM1/CD106 expressing cardiac fibroblasts restore the properties of ventricular walls by mobilizing lymphatic endothelial cell into the infarct.
Regarding the gene expression level of ADM and/or HHEX in the CD106+ and CD90+ fibroblasts, the instant specification teaches:
(D1) A method for producing a fibroblast highly expressing ADM, the method comprising: contacting TNF-α and IL-4 with a fibroblast; and culturing the fibroblast contacted, under a condition where ADM is capable of being highly expressed. (D2) The method according to (D1), wherein the fibroblast highly expresses VEGF-C. (D3) The method according to (D1) or (D2), wherein the fibroblast is CD106-positive. (D4) The method according to (D3), comprising selecting or concentrating a fibroblast highly expressing ADM, by use of an anti-CD106 antibody.
According to the instant specification, the culture of fibroblasts with TNFα and Il-4 afford a fibroblast population with increased CD106+ cells and CD90+ cells as well as high expression of ADM and VEGF-C. Thus, the fibroblasts of Iwamiya et al would have high expression of ADM and VEGF-C relative to a control fibroblast cell, such that the expression level of ADM and VEGF-C would be 1.2 times higher than in a control fibroblast cell.
Claim 33-36, 38, 39, 41, 42 and 44 are rejected under 35 U.S.C. 103 as being unpatentable over as Iwamiya (WO2018/155651, reference of the IDS filed 4/28/25) as evidenced by Iwamiya et al (US2019/0224250, reference of the IDS filed 4/28/25) in view of Iwamiya et al (PLoS One, 2020, Vol. 15, No. 9, article 0237810, reference of the IDS).
Iwamiya (‘250) teaches an (A1) injectable composition for treatment of a cardiac disease, the composition comprising fibroblasts, wherein the fibroblasts contain fibroblasts that are positive for vascular cell adhesion molecule-1 (VCAM-1, CD106). (A2) The injectable composition according to (A1), wherein the fibroblasts contain fibroblasts that are positive for Thymus cell antigen-1 (Thy-1, CD90) (paragraph [0008]).
Iwamiya (‘250) teaches that the fibroblasts are cardiac fibroblasts form adult tissue or cardiac fibroblasts isolated after differentiation of somatic stem cells (paragraph [0067]) which meets the limitations of claims 34 and 38.
Iwamiya teaches (‘250 ) (C1) A method for treatment of a heart disease, comprising carrying out injection of an injectable composition containing fibroblasts into a necrotic cardiac tissue region or a vicinity thereof, and/or infusion of the composition into a coronary artery, wherein the fibroblasts contain CD106-positive fibroblasts. (C2) The method for treatment of a heart disease according to (C1), wherein the fibroblasts contain CD90-positive fibroblasts (paragraph [0012]).
Iwamiya (‘250) teaches that CD106+CD90+ fibroblasts are capable of suppressing the progression of fibrosis (paragraph [0055] which meets the limitation of claim 35 35 as fibrosis is treated as a result of administration of the pharmaceutical composition
Iwamiya teaches (‘250) that heart disease in the present embodiment include, but are not limited to, diseases caused by disorder, deficiency, dysfunction, or the like of a myocardial tissue, such as heart failure, ischemic heart diseases, myocardial infarction, cardiomyopathy (paragraph [0051]),.
Iwamiya (‘250) does not teach the administration of the fibroblasts to a subject for amelioration of a condition of reduced lymphangiogenesis ability. Iwamiya et al do not specifically teach that the CD106+ and CD90+ fibroblasts produced by culture with TNFα and Il-4 highly express adrenomedullin and/or HHEX.
Iwamiya et al (PLoS One) teach that human cardiac fibroblasts expressing VCAM1 improve heart function in postinfarct heart failure rat models by stimulating lymphangiogenesis (title). VCAM1 is otherwise known as CD106. Iwamiya et al (PLoS One) teach that VCAM1 expressing cardiac fibroblasts when injected into the infarct restore the properties of ventricular walls by mobilizing lymphatic endothelial cell into the infarct (abstract)
It would have been prima facie obvious at the time prior to the effective filing date to administer the fibroblasts of Iwamiya et al (‘547) to subjects with heart failure after myocardial infarction to treat reduced lymphangiogenesis in the subjects by stimulating lymphangiogeneisi. One of skill in the art would have been motivated to do so by the teachings of Iwamiya et al (PLoS One) that VCAM1/CD106 expressing cardiac fibroblasts restore the properties of ventricular walls by mobilizing lymphatic endothelial cell into the infarct.
Regarding the gene expression level of ADM and/or HHEX in the CD106+ and CD90+ fibroblasts, the instant specification teaches:
(D1) A method for producing a fibroblast highly expressing ADM, the method comprising: contacting TNF-α and IL-4 with a fibroblast; and culturing the fibroblast contacted, under a condition where ADM is capable of being highly expressed. (D2) The method according to (D1), wherein the fibroblast highly expresses VEGF-C. (D3) The method according to (D1) or (D2), wherein the fibroblast is CD106-positive. (D4) The method according to (D3), comprising selecting or concentrating a fibroblast highly expressing ADM, by use of an anti-CD106 antibody.
According to the instant specification, the culture of fibroblasts with TNFα and Il-4 afford a fibroblast population with increased CD106+ cells and CD90+ cells as well as high expression of ADM and VEGF-C. Thus, the fibroblasts of Iwamiya et al would have high expression of ADM and VEGF-C relative to a control fibroblast cell, such that the expression level of ADM and VEGF-C would be 1.2 times higher than in a control fibroblast cell.
All claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAREN A CANELLA whose telephone number is (571)272-0828. The examiner can normally be reached M-F 10-6:30.
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KAREN A. CANELLA
Examiner
Art Unit 1643
/Karen A. Canella/Primary Examiner, Art Unit 1643