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 amendment and response received on 03/16/2026 has been entered. Claim 34 has been canceled. Claims 1, 6, 9, 10 and 12 are amended.
Claims 1, 2, 4, 6, 7, 9, 10, 12, 14, 16, 18-31 are currently pending and under examination in the instant application. An action on the merits follows. Claims 1, 6 9, 30 and 31 are independent claims.
Priority
Applicant's claim for the benefit of a prior-filed application filed 07/19/2022 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Thus, the earliest possible priority for the instant application is 07/19/2022.
Response to Arguments
Withdrawn objections/rejection in response to Applicants’ arguments or amendment
Claim Objection
The objection of claim 1 is withdrawn in view of applicant’s claim which now does not contain a comma in the phrase. Applicant’s argument with regard to a withdrawn objection are moot.
Claim Rejections - 35 USC § 102/103
The rejection of claim 34 is withdrawn in view of applicant’s cancellation of claim 34. Applicant’s argument with regard to a withdrawn rejection are moot.
Claim Rejections - 35 USC § 112(b)
In view of Applicants’ amendment of claims 1, 6, 9, 10 and 12 , the rejection of claims 1, 2, 4, 6-7, 9-10, 12, 14, 16, 18-31 and 34 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite has been withdrawn.
Applicant’s argument with regard to a withdrawn rejection are moot.
Maintained Claim Rejections in response to Applicants’ arguments
35 USC § 103
Claim 1, 2, 4, 6, 7, 9, 10, 12, 14, 16, 18-31 are rejected under 35 U.S.C. 103 as being unpatentable over Gotoh et al (US Patent Number. 11,299,712B2), Volckaert et al (Developmental Dynamics. 2015, Page 342-366), Marotta et al (Methods in Molecular Biology, Page 1-15), and Yamamoto et al (Nature Methods. 2017, Page 1097-1106; as cited in IDS).
Regarding claim 1, Gotoh teaches a method for producing type II alveolar epithelial cells from pluripotent stem cells and subjecting the alveolar epithelial progenitor cells obtained to three-dimensional culture in a medium (abstract) and ventral anterior foregut cells (a type of lung progenitor cell) obtained in a medium containing a GSK inhibitor, Fibroblast Growth Factor 10 (FGF10), keratinocyte growth factor (KGF), and a NOTCH signal inhibitor (Examiner notes that gamma secretase inhibitor is a NOTCH signal inhibitor as evidenced by Wikipedia (Page 2, Function; downloaded 1/2/2026) (col 2, lines 20-27 ; claim 1, step 4), rendering obvious a method for differentiating lung progenitor cells (LPC) into alveolar type 2 (AT2) cell comprising step (i) as recited in claim 1;
subjecting the induced alveolar epithelial progenitor cells obtained in Step (4) to three-dimensional culture in a basal medium supplemented with additives consisting of a steroid drug, a cAMP derivative, a phosphodiesterase inhibitor, and KGF (claim 1, step 5), rendering obvious step (ii) passaging the cells of (i) in a base culture medium as recited in claim 1, step (ii);
subjecting the induced alveolar epithelial progenitor cells obtained in Step (4) to three-dimensional culture in a basal medium supplemented with additives consisting of a steroid drug, a cAMP derivative, a phosphodiesterase inhibitor, and KGF (claim 1, step 5, Figure 12 shows 7 day culture), rendering obvious step (iii) culturing the cells of (ii) in a base culture medium, and step (v) passaging the cells of (iv) having expression of EpCAM and/or CPM in a base culture medium which comprises KGF, dexamethasone, cAMP, and an inhibitor of cyclic nucleotide phosphodiesterase as recited in claim 1;
a step of isolating carboxypeptidase M-positive (CPM-positive) cells (claim 1, step 4; Figure 1, 3, 4, and 12 show CMP+ cell- sorting), rendering obvious (iv) separating the cells of (iii) having expression of epithelial cellular adhesion molecule (EpCAM) and/or carboxypeptidase M (CPM) of claim 1;
a further step of isolating cells positive for one or more type II alveolar epithelial cell markers selected from the group consisting of surfactant protein C (SFTPC) (claim 1, step 5), rendering obvious (vi) separating the cells of (v) having expression of surfactant protein C (SFTPC) to form AT2 cells of claim 1.
Gotoh does not teach a base culture media that also comprises a GSK3 inhibitor and FGF10 at step (ii) and (iii) and ROCK inhibitor for about 24 to about 48 hours at step (ii).
However, Volckaert teaches WNT signaling and FGF10 are essential for epithelial branching and are required for primary lung bud formation (page 4, col 1, para 4 and page 10, col 2, heading), demonstrating that addition of these factors to the base culture media would be important to ensure proper and robust differentiation of progenitors towards the lung cell fate. Moreover, Marotta teaches that addition of ROCK inhibitor is a known method in the art of cell culture, particularly cells used for differentiation, to maximize survival of cells after passaging.
It would have been prima fascia obvious to one of ordinary skill in the art prior to the filing of the instant application to include GSK3 inhibitor, which causes increase WNT signaling, and FGF10 as taught by Volckaert in steps (ii) and (iii) of Gotoh as they are both important for guiding specification of lung progenitor cells at step (ii), (iii), and (v) and to include ROCKi as described by Marotta in step (ii) of Gotoh as it improves cell survival at passaging. One would be motivated to combine the teachings because they would maximize the efficiency of differentiation of lung progenitor cells towards the AT2 cell state and their survival. There would have been reasonable expectations of success in combining these teachings as one of ordinary skill in the art would recognize to combine known elements in the art to give predictable results.
Further, changes in the sequence of adding ingredients is generally considered prima facie obvious. See MPEP 2144.04 IV(C). Ex parte Rubin, 128 USPQ 440 (Bd. App. 1959) (Prior art reference disclosing a process of making a laminated sheet wherein a base sheet is first coated with a metallic film and thereafter impregnated with a thermosetting material was held to render prima facie obvious claims directed to a process of making a laminated sheet by reversing the order of the prior art process steps.). See also In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946) (selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results); In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930). Therefore, the order of addition of the culturing agents at the various steps as taught by the prior art references support a prima facie case of obviousness for the claimed invention.
Regarding claim 2, the combined teachings of Gotoh, Volckaert and Marotta render obvious claim 1.
Moreover, Gotoh teaches the passaging of (v) is performed in a two-dimensional (2D) matrix (Figure 1).
Regarding claim 4, the combined teachings of Gotoh, Volckaert and Marotta render obvious claim 1.
Moreover, Gotoh teaches the passaging of (v) is performed in a three-dimensional (3D) matrix (Figure 1, shows 3D culture after CDM+ cell sorting).
Regarding claim 6, Gotoh teaches a method for producing type
II alveolar epithelial cells from pluripotent stem cells and subjecting the alveolar
epithelial progenitor cells obtained to three-dimensional culture in a medium (abstract), ventral anterior foregut cells (a type of lung progenitor cell) obtained in a medium containing a GSK3 inhibitor, Fibroblast Growth Factor 10 (FGF10), keratinocyte
growth factor (KGF), a NOTCH signal inhibitor (gamma secretase inhibitor is a NOTCH signal inhibitor) (claim 1, step 4), rendering obvious a method for differentiating lung progenitor cells (LPC) into alveolar type 2 (AT2) cell comprising step (i);
a step of isolating carboxypeptidase M-positive (CPM-positive) cells (claim 1, step 4; Figure 1, 3, 4, and 12 show CMP+ cell- sorting), rendering obvious (ii) separating the cells of (iii) having expression of epithelial cellular adhesion molecule (EpCAM) and/or carboxypeptidase M (CPM);
subjecting the induced alveolar epithelial progenitor cells obtained in Step (4) to three-dimensional culture in a basal medium supplemented with additives consisting of a steroid drug, a cAMP derivative, a phosphodiesterase inhibitor, and KGF (claim 1, step 5; Figure 12), rendering obvious (iii) passaging the cells of (ii) having expression of EpCAM and/or CPM in a base culture medium comprising KGF, dexamethasone, cAMP, and an inhibitor of cyclic nucleotide phosphodiesterase and step (iv) culturing the cells of (iii) in a base culture medium comprising a KGF, dexamethasone, cAMP, and an inhibitor of cyclic nucleotide phosphodiesterases free of ROCKi for about 7 days;
further step of isolating cells positive for one or more type II alveolar epithelial cell markers selected from the group consisting of surfactant protein C (SFTPC) (claim 1, step 5), rendering obvious step (v) separating the cells of (iv) having expression of SFTPC to form AT2 cells.
Gotoh does not teach a base culture media that also comprises a GSK3 inhibitor and FGF10 at step (iii) and (iv) and ROCK inhibitor for about 24 to about 48 hours at step (iii).
However, Volckaert teaches WNT signaling and FGF10 are essential for epithelial branching and are required for primary lung bud formation (page 4, col 1, para 4 and page 10, col 2, heading), demonstrating that addition of these factors to the base culture media would be important to ensure proper and robust differentiation of progenitors towards the lung cell fate. Moreover, Marotta teaches that addition of ROCK inhibitor is a known method in the art of cell culture, particularly cells used for differentiation, to maximize survival of cells after passaging.
It would have been prima fascia obvious to one of ordinary skill in the art prior to the filing of the instant application to include GSK3 inhibitor, which causes increase WNT signaling, and FGF10 as taught by Volckaert in steps (ii) and (iii) of Gotoh as they are both important for guiding specification of lung progenitor cells at step (ii), (iii), and (v) and to include ROCKi as described by Marotta in step (ii) of Gotoh as it improves cell survival at passaging. One would be motivated to combine the teachings because they would maximize the efficiency of differentiation of lung progenitor cells towards the AT2 cell state and their survival. There would have been reasonable expectations of success in combining these teachings as one of ordinary skill in the art would recognize to combine known elements in the art to give predictable results.
Further, changes in the sequence of adding ingredients is generally considered prima facie obvious. See MPEP 2144.04 IV(C). Ex parte Rubin, 128 USPQ 440 (Bd. App. 1959) (Prior art reference disclosing a process of making a laminated sheet wherein a base sheet is first coated with a metallic film and thereafter impregnated with a thermosetting material was held to render prima facie obvious claims directed to a process of making a laminated sheet by reversing the order of the prior art process steps.). See also In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946) (selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results); In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930). Therefore, the order of addition of the culturing agents at the various steps as taught by the prior art references support a prima facie case of obviousness for the claimed invention.
Regarding claim 7, the combined teachings of Gotoh, Volckaert and Biology Marotta render obvious claim 6.
Moreover, Gotoh teaches the passaging of (iii) is performed in a three-dimensional (3D) matrix (Figure 1, shows 3D culture after CDM+ cell sorting).
Regarding claim 9, Gotoh teaches a method for producing type
II alveolar epithelial cells from pluripotent stem cells and subjecting the alveolar
epithelial progenitor cells obtained to three-dimensional culture in a medium (abstract), ventral anterior foregut cells (a type of lung progenitor cell) obtained in a medium containing a GSK inhibitor, Fibroblast Growth Factor 10 (FGF10), keratinocyte
growth factor (KGF), a NOTCH signal inhibitor (gamma secretase inhibitor is a NOTCH signal inhibitor) (claim 1, step 4), rendering obvious a method for differentiating lung progenitor cells (LPC) into alveolar type 2 (AT2) cell comprising step (i);
subjecting the induced alveolar epithelial progenitor cells obtained in Step (4) to three-dimensional culture in a basal medium supplemented with additives consisting of a steroid drug, a cAMP derivative, a phosphodiesterase inhibitor, and KGF (claim 1, step 5), rendering obvious step (ii) passaging the cells of (i) in a base culture medium, (iv) passaging the cells of (iii) having expression of EpCAM and/or CPM in a base culture medium, and (v) culturing the cells of (iv) in a base culture medium comprising KGF, dexamethasone, cAMP,and an inhibitor of cyclic nucleotide phosphodiesterases, free of ROCKi for about 7 days;
a step of isolating carboxypeptidase M-positive (CPM-positive) cells (claim 1, step 4; Figure 1, 3, 4, and 12 show CMP+ cell- sorting), rendering obvious (iii) separating the cells of (ii) having expression of epithelial cellular adhesion molecule (EpCAM) and/or carboxypeptidase M (CPM);
further step of isolating cells positive for one or more type II alveolar epithelial cell markers selected from the group consisting of surfactant protein C (SFTPC), rendering obvious (vi) separating the cells of (v) having expression of SFTPC to form AT2 cells.
Gotoh does not teach a base culture media that also comprises a GSK3 inhibitor and FGF10 at step (ii), (iv), and (v) and ROCK inhibitor at step (ii) and (iv).
However, Volckaert teaches WNT signaling and FGF10 are essential for epithelial branching and are required for primary lung bud formation (page 4, col 1, para 4 and page 10, col 2, heading), demonstrating that addition of these factors to the base culture media would be important to ensure proper and robust differentiation of progenitors towards the lung cell fate. Moreover, Marotta teaches that addition of ROCK inhibitor is a known method in the art of cell culture, particularly cells used for differentiation, to maximize survival of cells after passaging.
It would have been prima fascia obvious to one of ordinary skill in the art prior to the filing of the instant application to include GSK3 inhibitor, which causes increase WNT signaling, and FGF10 as taught by Volckaert in steps (ii) and (iii) of Gotoh as they are both important for guiding specification of lung progenitor cells at step (ii), (iv), and (v) and to include ROCKi as described by Marotta in step (ii) of Gotoh as it improves cell survival at passaging. One would be motivated to combine the teachings because they would maximize the efficiency of differentiation of lung progenitor cells towards the AT2 cell state and their survival. There would have been reasonable expectations of success in combining these teachings as one of ordinary skill in the art would recognize to combine known elements in the art to give predictable results.
Further, changes in the sequence of adding ingredients is generally considered prima facie obvious. See MPEP 2144.04 IV(C). Ex parte Rubin, 128 USPQ 440 (Bd. App. 1959) (Prior art reference disclosing a process of making a laminated sheet wherein a base sheet is first coated with a metallic film and thereafter impregnated with a thermosetting material was held to render prima facie obvious claims directed to a process of making a laminated sheet by reversing the order of the prior art process steps.). See also In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946) (selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results); In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930). Therefore, the order of addition of the culturing agents at the various steps as taught by the prior art references support a prima facie case of obviousness for the claimed invention.
Regarding claim 10, the combined teachings of Gotoh, Volckaert and Marotta render obvious claim 9.
Regarding claim 12, the combined teachings of Gotoh, Volckaert and Marotta render obvious claim 9. Moreover, the passaging of (iv) and/or the culturing of (v) are repeated before the separating of (vi) would be obvious to one of ordinary skill in the art as this would permit expansion of the desired cell population and increase production of cells.
Regarding claim 14, the combined teachings of Gotoh, Volckaert and Marotta render obvious claim 9.
Moreover, Gotoh teaches the passaging of (ii) is performed in a two-dimensional (2D) matrix (Figure 1).
Regarding claim 16, the combined teachings of Gotoh, Volckaert and Marotta render obvious claim 9.
Moreover, Gotoh teaches the passaging of (iv) is performed in a three-dimensional (3D) matrix (Figure 1, shows 3D culture after CDM+ cell sorting).
Regarding claim 18, the combined teachings of Gotoh, Volckaert and Marotta render obvious claim 9.
Moreover, Gotoh teaches wherein the GSK inhibitor is CHIR99021 (page 2, column 2, para 2).
Regarding claim 19, the combined teachings of Gotoh,Volckaert and Marotta render obvious claim 18.
Moreover, Gotoh teaches CHIR99021 concentration in a medium is, for example, 1 nM to 50 μM and wherein the GSK3~ inhibitor are present in the medium at concentration 1 to 3 μM (page 26, col 2, line 63; claim 12, Fig 1).
Regarding claim 20, the combined teachings of Gotoh, Volckaert and Marotta render obvious claim 1.
Moreover, Gotoh teaches wherein the FGF10 present in the medium at concentrations 10 to 100 ng/ml (claim 12, Fig 1).
Regarding claim 21, the combined teachings of Gotoh, Volckaert and Marotta render obvious claim 1.
Moreover, Gotoh teaches wherein KGF is present in the medium at concentration 10 ng/ml (claim 12, Fig 1).
Regarding claim 22, the combined teachings of Gotoh, Volckaert and Marotta render obvious claim 1.
Moreover, Gotoh teaches the NOTCH signal inhibitor (which is a gamma secretase inhibitor) is N-[N-(3, 5-difluorophenacetyl)-1-alanyl]-s-phenylglycinet-butyl ester (DAPT) (page 24, col 2, line 29).
Regarding claim 23, the combined teachings of Gotoh, Volckaert and Marotta render obvious claim 22.
Moreover, Gotoh teaches wherein NOTCH signal inhibitor (DAPT) are present in the medium at concentrations of 10 to 50 μM (claim 12, Fig 1).
Regarding claim 24, the combined teachings of Gotoh, Volckaert and Marotta render obvious claim 1.
Moreover, Gotoh teaches wherein the steroid drug are present in the medium at concentration 50 nM (claim 12, Fig 1).
Regarding claim 25, the combined teachings of Gotoh, Volckaert and Marotta render obvious claim 1.
Moreover, Gotoh teaches wherein cAMP derivative are present in the medium at concentration 100 μM (claim 12, Fig 1).
Regarding claim 26, the combined teachings of Gotoh, Volckaert and Marotta render obvious claim 1.
Moreover, Gotoh teaches the phosphodiesterase inhibitor is 3-isobutyl-1-methylxanthine (IBMX). (claim 12, Fig 1).
Regarding claim 27, the combined teachings of Gotoh, Volckaert and Marotta render obvious claim 26.
Moreover, Gotoh teaches phosphodiesterase inhibitor, and the KGF are present in the medium at concentration 100 μM (claim 12, Fig 1).
Regarding claim 28, the combined teachings of Gotoh, Volckaert and Marotta render obvious claim 1.
Moreover, Gotoh teaches the medium further comprises a ROCK inhibitor (claim 6).
Regarding claim 29, the combined teachings of Gotoh, Volckaert and Marotta render obvious claim 28.
Moreover, Gotoh teaches Y-27632 is present in the culture medium at a concentration of about 10 μM (Specification, Page 27, col, para 1).
Regarding claim 30, the combined teachings of Gotoh, Volckaert and Marotta render obvious claim 1.
Moreover, Gotoh teaches the AT2 cells made by method of claim 1 (Fig 1, 3, 4, and 12).
Regarding claim 31, the combined teachings of Gotoh, Volckaert and Marotta render obvious claim 30.
Moreover, Yamamoto teaches passages of alveolar stem cells in fibroblast-dependent alveolar organoids (page 11, column 2 para 2).
Response to Arguments as they apply to rejection of claims 1, 2, 4, 6, 7, 9, 10, 12, 14, 16, 18-31 under 35 USC § 103 as they applied to Gotoh, Volckaert, Marotta, and Yamamoto
Applicant's arguments filed 03/16/2026 have been fully considered but have not
been found persuasive in overcoming the rejection for reasons of record as discussed in
detail below.
On page 12-17 of Remarks filed by applicant on 03/16/2026, applicant argues 1) Gotoh does not teach or suggest all of the elements of the method of claim 1, therefore a prima facie case of obviousness has not been established. More specifically that there are several differences between Gotoh’s method and the method of claim 1. The applicant argues that the examiner’s arguments focus on steps 4 and 5 of Gotoh and not the other steps of Gotoh’s method. The applicant also argues 2) the prior art of Volckaert and Morotta, which are used to remedy the deficiencies from Gotoh, are applied by the rationale of “obvious to try” and none of the cited references provides guidance on which steps specifically the GSK inhibitor, FGF10, and ROCK inhibitor should be added and in what combination, and, therefore, the “obvious to try” rationale is erroneous. Applicant further argues that Volckaert and Marotta do not teach or suggest the additional elements of claim 1 that are missing from Gotoh. Finally, the applicant argues 3) the prior art of Yamamoto does not remedy the deficiencies of Gotoh, Volckaert, and Morotta and is only cited with regard to claim 31.
Regarding argument 1, as stated at page 12 of the office action filed 01/06/2026, applicant is directed to MPEP 2144.04 IV(C) where changes in the sequence of adding ingredients is generally considered prima facie obvious considered prima facie obvious. See also In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946) (selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results); In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930). Therefore, the order of addition of the differentiating agents at the various timepoints (e.g. steps (i)-(vi) in claim 1) as taught by the prior art references support a prima facie case of obviousness for the claimed invention. While Gotoh recites additional preceding steps (steps 1-3) from step 4, it is not necessary to address the preceding steps of the Gotoh method when examining the limitations of the instant applications’ claim. Rather, step 4 of Gotoh teaches all the limitations of claim 1 step (i), including the recitation of starting with “ventral anterior foregut cells” which read on “lung progenitor cells” from instant claim 1. Indeed, the method of Gotoh begins with pluripotent stem cells as starting material, hence one could start at a step where the cells are already “lung progenitor cells” (as recited in claim 1) which can be “ventral anterior foregut cells” as ventral anterior foregut cells are the progenitors of lung cells. Finally, independent claims 1, 6, and 9 recite the phrase “comprising”, indicating additional steps or agents may be present in the methods as claimed, hence the steps 1-3 recited in Gotoh could be included in methods recited by independent claims 1, 6, and 9 of the instant application.
It is additionally noted that independent claims 1, 6, and 9 each recite methods of differentiating lung progenitor cells into AT2 cells, but each recite a different order of steps, further exemplifying that changes in the sequence of adding ingredients is
generally considered prima facie obvious. See table below comparing steps of claims 1, 6, and 9 of instant application.
Underlined steps indicate difference between claims:
Claim 1
Claim 6
Claim 9
A method for differentiating lung progenitor cells (LPC) into alveolar type 2 (AT2) cells, comprising:
A method for differentiating LPC into AT2 cells, comprising:
A method for differentiating LPC into AT2 cells, comprising:
(i) culturing LPC in a base culture medium comprising a glycogen synthase kinase 3 (GSK3) inhibitor, keratinocyte growth factor (KGF), fibroblast growth factor 10 (FGF10), and a gamma secretase inhibitor;
(i) culturing LPC in a base culture medium comprising a GSK3 inhibitor, KGF, FGF 10, and a gamma secretase inhibitor
(i) culturing LPC in a base culture medium comprising a GSK3 inhibitor, KGF, FGF 10, and a gamma secretase inhibitor;
(ii) passaging the cells of (i) in a base culture medium comprising a GSK3 inhibitor, KGF, FGF 10, dexamethasone, cyclic adenosine monophosphate (cAMP), an inhibitor of cyclic nucleotide phosphodiesterases, and a Rho-associated, coiled-coil containing protein kinase (ROCK) inhibitor for about 24 hours to about 48 hours;
(ii) separating the cells of (i) having expression of EpCAM or CPM
(ii) passaging the cells of (i) in a base culture medium comprising a GSK3 inhibitor, KGF, FGF 10, dexamethasone, cAMP, an inhibitor of cyclic nucleotide phosphodiesterases, and a ROCK inhibitor;
(iii) culturing the cells of (ii) in a base culture medium comprising a GSK3 inhibitor, KGF, FGF 10, dexamethasone, cyclic adenosine monophosphate (cAMP), and an inhibitor of cyclic nucleotide phosphodiesterases for about 7 days;
(iii) passaging the cells of (ii) having expression of EpCAM or CPM in a base culture medium comprising a GSK3 inhibitor, KGF, FGF 10, dexamethasone, cAMP, an inhibitor of cyclic nucleotide phosphodiesterases, and a ROCK inhibitor at about 24 hours to about 48 hours after plating the cells of (ii)
(iii) separating the cells of (ii) having expression of EpCAM or CPM
(iv) separating the cells of (iii) having expression of epithelial cellular adhesion molecule (EpCAM) or carboxypeptidase M (CPM)
(iv) culturing the cells of (iii) in a base culture medium comprising a GSK3 inhibitor, KGF, FGF 10, dexamethasone, cAMP, and an inhibitor of cyclic nucleotide phosphodiesterases for about 7 days, wherein the base culture medium does not comprise or is essentially free of a ROCK inhibitor; and(v) separating the cells of (iv) having expression of SFTPC to form AT2 cells.
(iv) passaging the cells of (iii) having expression of EpCAM or CPM in a base culture medium comprising KGF, FGF 10, dexamethasone, cAMP, an inhibitor of cyclic nucleotide phosphodiesterases, and a ROCK inhibitor;
(v) passaging the cells of (iv) having expression of EpCAM or CPM in a base culture medium comprising a GSK3 inhibitor, KGF, FGF 10, dexamethasone, cAMP, and an inhibitor of cyclic nucleotide phosphodiesterases, and a ROCK inhibitor; and (vi) separating the cells of (v) having expression of surfactant protein C (SFTPC) to form AT2 cells.
(v) separating the cells of (iv) having expression of surfactant protein C to obtain AT2 cells, wherein AT2 cells are characterized by expression of SFTPC
(v) culturing the cells of (iv) in a base culture medium comprising KGF, FGF 10, dexamethasone, cAMP, an inhibitor of cyclic nucleotide phosphodiesterases, and a GSK3 inhibitor, wherein the base culture medium does not comprise or is essentially free of a ROCK inhibitor; and(vi) separating the cells of (v) having expression of SFTPC to form AT2 cells.
(vi) separating the cells of (v) having expression of surfactant protein C to obtain AT2 cells, wherein AT2 cells are characterized by expression of SFTPC
(vi) separating the cells of (iv) having expression of surfactant protein C to obtain AT2 cells, wherein AT2 cells are characterized by expression of SFTPC
Therefore, as changes in sequences/steps is generally considered prima facie obvious, there is no requirement for steps in a reference claim to read in the same sequential manner starting with step 1, and the phrase “comprising” in the instant claim 1, 6, and 9 could include additional steps/agents, the 103-rejection applying the teachings of Gotoh is maintained.
Regarding argument 2, the examiner refers applicants to the reasons already of record and the reasons set forth in the paragraph above. Moreover, the examiner refutes the assumption of “obvious to try”, as interpreted by the applicant, and instead directs applicant to “teaching, suggestion, or motivation” rationale. Regarding the prior art of Volckaert, although Volckaert does not specifically indicate which parameters are critical or which possible choices would be successful as applied to the claimed invention as it pertains to inclusion of FGF and WNT activators in the methods steps, the prior art does provide details pertaining the need of FGF and WNT signaling during the lung formation process. Volckaert recites “FGF signaling is a critical component of the gene regulatory network regulating lung development, including maintenance of progenitor cell populations, epithelial and mesenchymal patterning and differentiation as well as branching morphogenesis. Several FGF ligands are expressed in the developing lung, including Fgf7, Fgf8, Fgf9, Fgf10, and Fgf18. Of these, only FGF10 is absolutely
required for initial lung formation.” (page 345, left col, para 2). Volckaert further teaches that during primary lung field specification “Wnt and FGF signaling are part of a feed-forward loop, similar to what has been reported in the distal lung mesenchyme” (page 351, left col, para 1), further indicating their combination in lung differentiation is important. In light of these teachings from Volckaert that FGF and WNT signaling are required during a specific window of the early lung differentiation and the fact that FGF10 and a GSK3 inhibitor are included in the protocol by Gotoh, it would have been prima facie obvious to time the inclusion of FGF10 and a WNT activator (i.e. GSK inhibitor) before the cells are differentiated into AT2 cells and one would have a reasonable expectation of success. Furthermore, Marotta teaches that ROCKi promotes survival and cloning efficiency when passaging and recovering iPSCs, hence it would have been prima facie obvious to include ROCKi in any step that includes passaging. Therefore, as Volckaert teaches the necessity of FGF10 and WNT activation in early stages of lung differentiation and Marotta teaches the ROCKi aids in survival of iPSCs during passage, the 103-rejection applying the teachings and motivations of Gotoh, Volckaert, and Marotta is maintained.
Regarding argument 3, in regards to the Yamamoto reference, while it does not remedy alleged deficiencies by Gotoh, Volckaert, and Marotta, it does teach passage of alveolar stem cells in fibroblast-dependent alveolar organoids to render obvious claim 31.
New Claim Rejections in response to Applicants’ arguments or amendment
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.
Claim 1, 6 and 9 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 (line 19), claim 6 (line 20), and claim 9 (line 18), are vague and indefinite in the recitation of “wherein AT2 cells are characterized by expression of SFTPC”. It is unclear what “characterization by expression” indicates as it could be interpreted as the characterization being SFTPC is expressed, not expressed, expressed in a particular pattern, etc. The specification does not describe any such characterization. As such the metes and bounds of the claim are indefinite.
Conclusion
Claims 1, 2, 4, 6, 7, 9, 10, 12, 14, 16, 18-31 are rejected.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Juliana Candelaria whose telephone number is (571)272-5488. The examiner can normally be reached Monday - Friday 8am - 5pm.
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, Maria Leavitt can be reached at (571) 272-1085. 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.
/JULIANA IRENE CANDELARIA/ Examiner, Art Unit 1634
/MARIA G LEAVITT/ Supervisory Patent Examiner, Art Unit 1634
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