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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 03/25/2026 has been entered.
Claims 1, 2, 6, 10 and 12-22 are pending in this application and Claim 12 is acknowledged as withdrawn, Claims 1, 2, 6, 10 and 13-22 were examined on their merits.
The rejection of Claims 1-2, 6, 10 and 13-22 are rejected under 35 U.S.C. 103 as being unpatentable over de Lima (2008) in view of Sigounas et al (U.S. PGPUB 20020169128), Doran et al (1991), Vacanti et al (U.S. 20150110749), Chiou et al (U.S. PGPUB 20140093486) and Bacigalupo et al (2009), has been withdrawn due to the Applicant’s amendments to the claims filed 02/03/2026.
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 1, 2, 6, 10 and 13-22 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 broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance, Claim 1 recites the broad recitation, “a subject diagnosed with a disease associated with tissue dysfunction, wherein said tissue is selected from the group consisting of a pulmonary tissue, a cardiac tissue, a hepatic tissue, a pancreatic tissue, a brain tissue, a nephric tissue and an ovarian tissue”, and the claim also recites “wherein the tissue associated with said dysfunction is a pulmonary tissue” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 1 also recites the limitation "said dysfunction" in Line 18. There is insufficient antecedent basis for this limitation in the claim as it is unclear if the tissue dysfunction being referred to is limited to “pulmonary tissue” or refers to one of the other tissue dysfunctions recited in the preamble. Claims 2, 6, 10 and 13-22 are rejected as being dependent upon rejected Claim 1 and for failing to resolve the indefiniteness thereof.
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.
Claims 1, 2, 6, 10, 13, 14, 15 and 17-22 are rejected under 35 U.S.C. § 103 as being unpatentable over de Lima et al. (2008), of record, in view of Aswanetmanee et al. (04/15/2015), Anversa et al. (US 2013/0216508 A1), and as evidenced by Sigounas et al. (US 20020169128), of record, and Bacigalupo et al. (2009), of record.
de Lima teaches that a method of treating acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML) comprising:
conditioning a subject for hematopoietic transplantation of culture expanded hematopoietic progenitor cells,
and that there is a need for methods to increase the amount of hematopoietic progenitor cells for transplantation (Abstract and Pgs. 771-772, Introduction), and reading on Claim 1.
de Lima teaches a treatment method comprising: (a) conditioning a human subject by:
(i) administering to the subject a therapeutically effective amount of busulfan/BU (a chemical alkylating agent, which induces tissue damage and ablates resident stem cells) and subsequently (ii) subjecting said subject a second therapeutically effective amount of busulfan; and (b) transplanting by infusion ex vivo cultured expanded human progenitor cells in suspension to said subject (see Pg. 722, Col. 2 and Pg. 773, Col. 2), and reading on Claims 1, 10, 13-15, 17 and 19.
Regarding Claim 6, de Lima teaches transplanted progenitor cells engrafted into the patients (Abstract); reads on progenitor cells which are “capable of” regenerating a structural/functional tissue.
Regarding Claim 18, de Lima teaches busulfan (agent capable of inducing damage to tissue) is administered to the subject 2 days prior to the second dose of busulfan (agent which ablates resident stem cells) because first dose of busulfan is administered on day -8 and followed by daily dose at day -6 (Pg. 772, Col. 2).
Regarding Claims 20-21, de Lima teaches said transplanting is by
intravenous route, infusion (Pg. 773, Col.. 2).
Regarding Claim 22, de Lima teaches the method further comprising treating the subject with an immunosuppressive regimen: fludarabine (Pg. 773, Col. 2).
de Lima does not teach the ALL or AML diagnosis is a disease diagnoses associated with pulmonary tissue dysfunction, as required by Claim 1;
that the human progenitor cells for transplantation include ex vivo human stem cells from pulmonary tissue, as required by Claim 2.
Aswanetmanee et al. teaches pulmonary complications, including leukostasis, occur in up to 80% or all leukemia patients and are a major cause of death (Pg. 18, Column 2, Lines 17-19), wherein leukostasis is characterized by tissue hypoxia (damage) (Pg. 17, Column 2, Lines 9-12) and wherein AML and ALL are characterized by pulmonary complications such as leukostasis (Pg. 19, Table 1). Therefore, the teachings of Aswanetmanee establish that the ALL or AML diagnosis in de Lima's subjects is a disease diagnoses associated with pulmonary tissue dysfunction.
Anversa et al. teaches obtaining and culturing ex vivo lung stem cells which may be from adult lung tissue (Pg. 2, Paragraphs [0019] and [0028]);
wherein the lung stem cells may be a heterogenous population (Pg. 8, Paragraph [0133]);
and wherein the lung stem cells can be implanted to treat damaged and/or defective lungs (Pg. 4, Paragraph [0060])
Sigounas et al. evidences that busulfan is known to damage pulmonary tissue (see paragraph [0004]). Therefore, de Lima’s busulfan is an agent which induces damage to the tissue associated with said dysfunction.
Bacigalupo evidences condition regimens for hemopoietic transplant involving busulfan are myeloablative (Pg. 1629 and Table 1). Bacigalupo teaches total body irradiation at a dose equal to or greater than 5 Gy is an alternative myeloablative treatment to busulfan (see Table 1). Therefore, de Lima’s busulfan is an agent which ablates said resident stem cells in said tissue.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to modify the method of de Lima and Aswanetmanee of conditioning a human subject diagnosed with a disease associated with pulmonary tissue dysfunction and then transplanting by infusion ex vivo expanded human progenitor cells in suspension to said subject to use a heterogenous population of ex vivo expanded, pluripotent cells from human, adult lung tissue as taught by Anversa because one would expect that lung stem cells would be uniquely suitable to treat damaged lung tissue. Those of ordinary skill in the art would have been motivated to make this modification in order to treat pulmonary tissue dysfunction in subject’s diagnosed with ALL or AML. There would have been a reasonable expectation of success in using the ex vivo expanded pluripotent cells from human, adult lung tissue of Anversa in de Lima's method because both references are drawn to the same field of endeavor, that is, the treatment of disease and/or tissue dysfunction by the administration of ex vivo expanded human progenitor cells.
Claims 1, 2, 6, 10, 13, 14, 15, 16 and 17-22 are rejected under 35 U.S.C. § 103 as being unpatentable over de Lima et al. (2008), of record, in view of Aswanetmanee et al. (04/15/2015), Anversa et al. (US 2013/0216508 A1), and as evidenced by Sigounas et al. (US 20020169128), of record, and further in view of Bacigalupo et al. (2009), of record.
The teachings of de Lima, Aswanetmanee and Anversa were discussed above.
None of the above references taught a method wherein total body irradiation (TBI) dose within the range of 1-7.5 Gy is used to ablate resident stem cells, as required by Claim 16.
Bacigalupo teaches condition regimens for hemopoietic transplant involving busulfan are myeloablative (Pg. 1629 and Table 1). Bacigalupo teaches total body irradiation at a dose equal to or greater than 5 Gy is an alternative myeloablative treatment to busulfan (see Table 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to modify the method of de Lima and Aswanetmanee of conditioning a human subject diagnosed with a disease associated with pulmonary tissue dysfunction by treating the subject with the myeloablative agent busulfan to substitute the TBI method of Bacigalupo for the busulfan treatment because both methods are art-recognized equivalent methods for myeloablation.
See the MPEP at 2144.06, II. Those of ordinary skill in the art would have been motivated to make this modification based on the availability of compounds or equipment and artisan preference. There would have been a reasonable expectation of success in making this substitution because both TBI and busulfan are both known in the art as myeloablatives.
Response to Arguments
Applicant’s arguments, see Remarks, filed 02/03/2026, Pg. 7, Lines 5-8 with respect to the rejection(s) of claim(s) 1, 2, 6, 10 and 13-22 under 35 U.S.C. § 103 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Anversa et al. (US 2013/0216508 A1), as set forth above.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to PAUL C MARTIN whose telephone number is (571)272-3348. The Examiner can normally be reached Monday-Friday 12pm-8pm EST.
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If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Sharmila G Landau can be reached at (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL C MARTIN/ Examiner, Art Unit 1653 06/02/2026
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