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
This action is in response to the papers filed on 02/04/2026. Claims 9, 10-12, 14, 24-25, 31-32, 34-37, 39-40, 42-45 and 49-55 are currently pending. Claims 9, 12, 24, 32, 34-35 and 39-40 having been amended, claims 1-5, 8, 16-20 and 22-23 have been cancelled, and claims 49-55 having been newly added as per claims filed on 02/04/2026.
Applicant’s election of Group II, which include claims 9-12 and 14 drawn to a method of enrichment of small airway and alveolar epithelia progenitor cells from distal lung tissue in the reply filed on 02/04/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election was treated as an election without traverse (MPEP § 818.01(a)). New claims 49-55 also read on the elected invention.
Claims 24-25, 31-32, 34-37, 39-40, and 42-45 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to non-elected subject matter, there being no allowable generic or linking claim.
Applicant asserts at Pg. 8 of remarks filed 02/04/2026 that “The claims of Groups IV, V and VI are amended and now depend directly or indirectly on claim 9 of elected Group II. Groups IV, V and VI are directed to related methods and systems.” Applicant further requests rejoinder of Groups IV, V and VI once an allowable claim is found and the claims of Groups IV, V and VI contain the limitations of the allowable claim. Such is not persuasive.
Though claims 24, 32 and 34 have been amended to depend on claim 9 of elected Group II, the methods of Groups I-VI lack unity of inventions as set forth in the restriction requirement filed on 12/04/2025 which has not been rebutted by Applicants.
The requirement for restriction between Groups I-VI is still deemed proper and is therefore made FINAL.
Therefore, claims 9-12, 14, and 49-55 are subject to examination to which the following grounds of rejection are applicable.
Priority
The instant application a 371 of PCT/US2021/030280 filed 04/30/2021, which claims priority to PCT/US2021/030280 filed 07/21/2020. PCT/US2021/030280 claims priority to PRO 63/054,440, PRO 63/019,217, and PRO 63/019,140 all filed on 05/01/2020.
Thus, the earliest possible priority for the instant application is 05/01/2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 10/25/2022 and 02/04/2026 were filed before the mailing date of the non-final office action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 9 is objected to because the recitation of “aveolar” in line 2 is grammatically incorrect. Appropriate correction is required.
Claim 14 is objected to because the recitation of “aveolar” in line 2 is grammatically incorrect. Appropriate correction is required.
Claims 12, 14, 51, 52 and 55 are objected to because of the following informalities. Each of these claims refers to the method (method of enrichment) of a preceding claim 9 by use of an indefinite article “A”. The use of an indefinite article in this context is grammatically incorrect, i.e. the definite article --the-- should be used in this context. For example, “A” (claim 12) “method of claim 9…” should be --The-- “method of claim 9…”. Appropriate correction is required.
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 9-12, 14, and 49-55 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 applicant regards as the invention.
Claim 9 recites “A method of enrichment and optionally sub setting” at line 1, “processing and optionally freezing lung tissues, cells or both” at line 3, and “optionally drying the pieces of lung tissue” at line 6. This claim is indefinite because it is unclear if the “optionally” recited items are intended to be recited in the alternative or as an addition to the non-optional items. For the purposes of examination, the claim is interpreted as NOT requiring the “sub setting”, “freezing” , or “drying”.
Claim 9 recites at line 3 “processing and optionally freezing lung tissues, cells or both, comprising”. The steps recited for the method of instant claim 9 are tissue processing steps. Therefore, it is unclear how the steps, such as cutting tissue, could reasonably be applied to “cells or both”. This lack of clarity renders the claim indefinite as one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. As such the metes and bounds of the claim are indefinite.
Claim 9 recites at line 8 “further cutting the pieces of lung tissue into about 0.5-5.0 mm diameter pieces, wherein the lung tissue is distal lung tissue, and further cutting the lung tissue into about 0.5-5.0 mm diameter pieces comprises cutting the lung tissue into about 0.5-1.5 mm diameter pieces…”. As written, is unclear whether the claimed final tissue pieces are required to be 0.5-5.0 mm or 0.5-1.5 mm or whether both ranges define separate cutting stages. This lack of clarity renders the claim indefinite as one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Note that a broad range or limitation is together with a narrow range of limitation that falls within the broad range or limitation (in the same claim) is considered indefinite since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. In the present instance, claim 9 recites the broad recitation “0.5 cm3 to 2.0 cm3 pieces”, and the claim also recites specific smaller sizes of the same lung tissues pieces which is the narrower statement of the range/limitation (e.g., 0.5-5.0 mm diameter, 0.5-1.5 mm). As such the metes and bounds of the claim are indefinite.
Claim 9 is rejected because of its recitation of “removing visceral pleura from the pieces of lung tissue”. It is unclear if the removal takes place before washing the pieces or after washing the pieces of tissue to remove blood. As such the metes and bounds of the claim are indefinite. Claims 10-12, 14 and 49-55 are dependent upon and inherit the deficiencies of claim 9. Please note as set forth in the claim objection that claim 53 recites “a method of claim 1…”. (See 112b rejection of claim 53 below). However, for the sake of compact prosecution it will be considered for examination purposes that the applicants’ intention was that claim 53 depend from claim 50 (and ultimately claim 9) as it provides a narrower temperature within the range of claim 50.
Claim 10 recites “The method of claim 9, wherein cutting the lung tissue into about 0.5-1.5 mm diameter pieces comprises first cutting the 0.5-5.0 mm diameter pieces of lung tissue into about 1.5-2.5 mm diameter pieces, and then cutting the 1.5-2.5 mm diameter pieces
into about 0.5-1.5 mm diameter pieces.” It appears the applicant intended to claim the staged sequence of cutting as follows: .05mm – 5.0mm cut to 1.5mm – 2.5mm cut to 0.5-1.5mm. However, claim 9 does not explicitly require the first intermediate .05-mm-5.0mm as separate step before the .05-1.5mm cutting. The pieces required by claim 10 during this sequence are not required and may not exist as a separate intermediate product in claim 9. Therefore, there is lack of express antecedent basis for those specific pieces and the claim is rendered indefinite.
Claim 11 is dependent upon and inherit the deficiencies of claim 10.
Claim 49 recites “The method of claim 9, further comprising identifying and separating the proximal and distal regions”. However, claim 9 is limited to reciting distal lung tissue. Therefore, there is lack of express antecedent basis for those specific spatial orientation of these pieces with respect to “the proximal region” and the claim is rendered indefinite.
Claim 50 recites at line 3 “…placing the about 0.5-5.0 mm diameter pieces of lung tissue into a vial and cryoprotective media; and freezing the vial comprising the 0.5-5.0 mm diameter pieces of lung tissue…”. Claim 9 ultimately requires tissue pieces of about 0.5-1.5 mm, which is a narrower limitation than the recited 0.5-5.0 mm diameter of claim 50. Therefore, it is unclear what pieces the applicant intends for freezing within the invention. Does this refer to an intermediate product or the final product recited within the claim? This lack of clarity renders the claim indefinite.
Claim 51 recites “A method of claim 9, further comprising freezing the 0.5-5.0 mm diameter pieces of lung tissue in vapor phase of a liquid nitrogen vessel.” Claim 9 ultimately requires tissue pieces of about 0.5-1.5 mm, which is a narrower limitation than the recited 0.5-5.0 mm diameter of claim 51. Therefore, it is unclear what pieces the applicant intends for freezing within the invention, e.g., 0.5-5.0 mm, 0.5-1.5 mm. This lack of clarity renders the claim indefinite.
Claim 52 recites “A method of claim 9, wherein cutting lung tissue into about 0.5 cm3 to 2.0 cm3 pieces comprising cutting lung tissue into about 1.0 cm3 pieces, or wherein further cutting the lung tissue into about 0.5-5.0 mm diameter pieces comprising cutting the lung tissue into about 2-5 mm diameter pieces, or wherein cutting the lung tissue into about 3-4 mm diameter pieces, or wherein further cutting the lung tissue into about 0.5-5.0 mm diameter pieces
comprising cutting the lung tissue into about 3-4 mm diameter pieces.” It is unclear exactly what the applicant intends to claim as multiple alternative tissue size limitations are recited that are inconsistent with the tissue sizes recited in the dependent claim 9. As claim 9 ultimately requires tissue pieces of about 0.5-1.5 mm. It is unclear what the applicant intends for the claimed method to require final tissue pieces of 0.5-1.5 mm, 2-5 mm, 3-4 mm or some combination thereof. This lack of clarity renders the claim indefinite as one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. As such the metes and bounds of the claim are indefinite.
Claim 53 recites “The method of claim 1…”. Claim 1 is a cancelled claim., it is unclear to which claim that claim 53 was meant to depend from. Thus, the metes and bounds of the claim cannot be determined and the claim is rendered indefinite.
Applicant is required to cancel the claim(s), or amend the claim(s) to place the claim(s) in proper dependent form, or rewrite the claim(s) in independent form. Therefore, the metes and bounds of claims 32 and 34 are indefinite. For the sake of compact prosecution claim 53 has been interpreted as depending on claim 9.
Claim 54 recites, “optionally have a negative staining for DAPI.” at line 3. This claim is indefinite because it is unclear if the “optionally” recited item is intended to be recited in the alternative or as an addition to the non-optional item. For the purposes of examination, the claim is interpreted as NOT requiring a “negative staining for DAPI”.
Claim 55 recites “The method of claim 9, wherein selecting epithelial progenitor cells comprising depleting immune cells and endothelial cells, cell surface staining for Fluorescence associated cell sorting (FACS), or both.” However, as written it is unclear whether FACS sorting is actually performed or if only the staining for FACS sorting is performed. This lack of clarity renders the claim indefinite as one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. As such the metes and bounds of the claim are indefinite.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 9-12, 14, 49, 52, and 54-55 are rejected under 35 U.S.C. 103 as being unpatentable over Zacharias et al. (William Zacharias et al., Protocol exchange, 2018; hereafter “Zacharias”) as evidenced by Barkauskas et al. (Barkauskas CE et al., Development, 2017)
Regarding Claim 9-11 and 52, The instant claim 9 is drawn to a method with the following requirements: cutting lung tissue into about 0.5cm3 to 2.0 cm3 pieces, washing the cut lung pieces, removing visceral pleura from the cut lung pieces, cutting the pieces into 0.5-5.0mm diameter pieces, cutting the pieces again into 0.5-1.5 diameter pieces, digesting the 0.5 – 1.5mm diameter pieces with enzyme, dissociating the digested pieces into single cells, and then selecting epithelial progenitor cells. Claims 10-11 are drawn to cutting the lung tissue of claim 9 into progressively small pieces of specific size. Claim 52 is drawn to cutting the lung tissue of claim 9 into specific sizes. (Please see 112b rejection above in relation to the indefinite nature of the recited cut lung pieces size).
Zacharias teaches a method for Isolation and culture of human alveolar epithelial
progenitor cells (Title). Specifically, Zacharias teaches “Here we describe the techniques used for isolation and 3D organoid formation of alveolar epithelial progenitor cells from primary human lungs. We describe the selection, digestion, single cell suspension, antibody staining, and culture techniques used for these assays.” (Abstract). Zacharias teaches removal of the visceral pleura and emphasis the importance to do so to prevent negatively effecting the digestion (Pg. 2, Procedure Section). Zacharias teaches cutting the lung tissue into progressively smaller pieces (Pg. 2, Procedure Section). Digestion using enzyme solution containing collagenase, dispase, and DNase. (Pg. 2, Procedure, second line). Zacharias teaches bead sorting to select alveolar epithelial progenitor cells (Pg. 3, from step 19.)
Zacharias does not teach the lung tissue pieces are cut into pieces of the exact diameter ranges recited in the instant claims. However, a person having ordinary skill in the art would understand the need to cut smaller pieces of lung tissue from larger pieces of lung tissue for more efficient digestion and filtration of tissue. Moreover, a person of ordinary skill in the art would have been motivated to determine an appropriate size of lung tissue through routine optimization within a method for isolation of primary cells from tissue that would allow for the most successful digestion and filtration without having clogs to achieve a desired population of viable cells. See MPEP 2144.05 II. A. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.")
Regarding Claim 12, Zacharias teaches digestion using enzyme solution containing collagenase, dispase, and DNase. (Pg. 2, Procedure, second line).
Regarding Claim 14, Zacharias teaches the population of cells selected from their method to be HTII-280-positive, specifically “This population of cells are HT280+Tm4sf1+ human AEPs.” (Pg. 4, line 12).
Regarding Claim 49, Zacharias teaches the method of claim 9 as discussed above. Zacharias does expressly teach identifying and separating proximal and distal regions of lung tissue before cutting them. However, it would have been obvious to one of ordinary skill in the art to select and process the region of tissue containing the cells of interest as it was well known in the art prior to the instant application that proximal and distal regions of the lung contain specific cell populations specialized for different functions. This is evidenced by the teachings of Barkauskas et al. (Abstract, Introduction). (Please also see 112b rejection above)
Regarding Claim 54, the alveolar epithelial progenitor cells isolated by Zacharias would inherently be CD45- absent evidence to the contrary as CD45+ is a pan leukocyte marker and alveolar epithelial progenitor cells are distinct cell type that are not leukocytes.
Regarding Claim 55, Zacharias teaches their method to include FACs sorting of cells (Pg. 3-4, beginning from step 16).
Claims 50-51 and 53 are rejected under 35 U.S.C. 103 as being unpatentable over Zacharias et al. (William Zacharias et al., Protocol exchange, 2018; hereafter “Zacharias”) as applied to claim 9 above and in view of Andreasen et al. (US11484025B2; hereafter “Andreasen”)
Regarding Claims 50-51 and 53, Zacharias teaches the method of claim 9 as discussed above. Zacharias does not teach the freezing of lung tissue into cryoprotective media and freezing to about -90 to -70 degrees C as in instant claim 50, about -80 degrees C as in claim 53, or the freezing in vapor phase as in claim 51.
Andreasen cures the deficiencies of Zacharias as Andreasen teaches cryopreservation methods of tissue (Column 1, Background of the Invention Section), including lung (Column 7, lines 47-48). Freezing can be done to about -80 degrees C and freezing can further be done in liquid nitrogen or vapor phase (Column 24, lines 3-7).
It would have been obvious to a person having ordinary skill in the art at the time of the instant application to have modified the method for isolating cells from lung tissue as described by Zacharias to further include the step of a cryopreservation method as taught by Andreasen. One would be motivated to freeze isolated cells to allow for future experimentation or cell culture of the isolated cells as is done routinely in the art. 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.
Conclusion
Claims 9-12, 14, and 49-55 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KODYE LEE ABBOTT whose telephone number is (703)756-1111. The examiner can normally be reached M-F 8-5.
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/KODYE LEE ABBOTT/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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