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Claims 1, 2, 6, 10 and 12-22 are pending in this application, Claim 12 is acknowledged as withdrawn, Claims 1, 2, 6, 10 and 13-22 were examined on their merits.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 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as the invention, for reciting a broad range or limitation together with a narrow range or limitation, have been withdrawn upon reconsideration of the rejection.
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.
Claim 1 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 dysfunction being referred to is the "pulmonary tissue" recited in Line 11 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 newly 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, Bacigalupo et al. (2009), of record, Avni et al. (2011) and Ayhan et al. (2014), as necessitated by Applicant’s amendment to the claims filed 09/03/2026.
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:
administering to the subject a therapeutically effective amount of busulfan/BU (a chemical alkylating agent, which induces tissue damage and ablates resident stem cells);
subsequently subjecting said subject a second therapeutically effective amount of busulfan;
and 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).
With regard to the limitation of Claim 1, “wherein when said disease is cancer, said cancer is a solid tumor”, new reference Avni et al. teaches that myeloid sarcoma is reported in 2-8% of patients with AML either as a single or multifocal (solid) tumor (Pg. 310, Column 1, Lines 6-7) while newly cited reference Ayhan et al. teaches myeloid sarcoma is reported in 2-14% of patients with AML (Pg. 1, Column 1, Lines 7-8) and describes myeloid sarcoma as developing as a secondary malignancy in children treated for acute lymphoblastic leukemia (Pg. 1, Abstract). Thus, it would have been apparent to the ordinary artisan that the treated subjects with acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML) of de Lima et al., can also manifest solid tumors (myeloid sarcoma).
de Lima does not teach wherein the ALL or AML diagnosis is associated with pulmonary tissue dysfunction, as required by Claim 1;
or 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, Avni et al. (2011) and Ayhan et al. (2014).
The teachings of de Lima, Aswanetmanee, Anversa, Bacigalupo, Avni and Ayhan 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 further 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 at least 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 09/03/2026, with respect to the withdrawn rejection under 35 U.S.C. § 112(b) or 35 U.S.C. §112 (pre-AIA ), second paragraph have been fully considered and are persuasive. The remaining rejections have been considered insofar as they apply to the pending and new rejections herein.
The Applicant argues that “said dysfunction” does not lack antecedent basis as it clearly refers to the “tissue dysfunction recited earlier in Claim 1 (Remarks, Pg. 7, Lines 22-24).
This is not found to be persuasive for the following reasons, as discussed above, it is unclear if the “dysfunction” being referred to on Line 18 of Claim 1 is the "pulmonary tissue" recited in Line 11 or refers to one of the other “tissue dysfunctions” recited in the preamble.
The Applicant argues that the Anversa PGPUB is based on the same or substantially the same data used in a now retracted NPL (Remarks, Pg. 9, Lines 5-33 and Pg. 10, Lines 1-9).
This is not found to be persuasive for the following reasons, Applicant has provided no evidence on the record to overcome the use of the Anversa PGPUB as valid prior art. As Applicant is no doubt aware, the cited prior art is presumed to be operable/enabled in the absence of evidence to the contrary. See the MPEP at 2121, I.
The Applicant asserts that arguendo, Anversa does not remedy the alleged deficiencies of the rejection as the reference does not teach or suggest the claimed conditioning protocol or provide a reason to utilize the method of de Lima to treat a solid tumor cancer as now recited by Claim 1 (Remarks, Pg. 10, Lines 10-17).
This is not found to be persuasive for the following reasons, as discussed in the new rejections above, de Lima teaches the claimed conditioning protocol while Avni et al. teaches that myeloid sarcoma is reported in 2-8% of patients with AML either as a single or multifocal (solid) tumor *Pg. 310, Column 1, Lines 6-7) while Ayhan et al. teaches myeloid sarcoma is reported in 2-14% of patients with AML (Pg. 1, Column 1, Lines 7-8) and describes myeloid sarcoma as developing as a secondary malignancy in children treated for acute lymphoblastic leukemia (Pg. 1, Abstract). Thus, it would have been apparent to the ordinary artisan that the treated subjects with acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML) of de Lima et al., can also manifest solid tumors (myeloid sarcoma). The Examiner notes that Anversa was cited only for its’ teaching of 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]). It would therefore have been obvious to one of ordinary skill in the art 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.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 PAUL C MARTIN whose telephone number is (571)272-3348. The Examiner can normally be reached Monday-Friday 12pm-8pm EST.
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, 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.
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.
/PAUL C MARTIN/ Examiner, Art Unit 1653
/SHARMILA G LANDAU/ Supervisory Patent Examiner, Art Unit 1653
