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 .
Status of the Claims
Claims 1-4, 7, 9-11, 15-21, 23, 30-32, and 36-37 are pending.
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.
Claim 23 is 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 23 recites the limitation "the pharmaceutical composition of claim 22". Claim 22 is cancelled. There is insufficient antecedent basis for this limitation in the claim.
The previous claim set included claim 22 which read, “the pharmaceutical composition of any one of claims 1-21, wherein the subject is treated or has been treated with an MDS treatment”.
For purposes of examination, claim 23 will be interpreted as “The pharmaceutical composition of claim 1, wherein the subject is treated or has been treated with an MDS treatment, wherein the MDS treatment is a hypomethylating agent…”
Appropriate correction is required.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 30-32, and 36-37 are rejected under 35 U.S.C. 102(A)(1) as being anticipated by
Jacoby, Elad, et al. "First-in-human mitochondrial augmentation of hematopoietic stem cells in Pearson syndrome." Blood 132 (2018): 1024. (Provided in IDS of 5/29/2024)
As evidenced by Magnon C, Frenette PS. Hematopoietic stem cell trafficking. 2008 Jul 14. In: StemBook [Internet]. Cambridge (MA): Harvard Stem Cell Institute; 2008
As evidenced by Farruggia, P. et al. (2015). Pearson Syndrome: A Retrospective Cohort Study from the Marrow Failure Study Group of A.I.E.O.P. (Associazione Italiana Emato-Oncologia Pediatrica). In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 26
Regarding claim 30, Jacoby et al. teaches enrichment of Pearson Syndrome (PS)-derived HSCs with wild-type mitochondria, and reports on three patients with PS treated with autologous HSCs following ex-vivo mitochondrial augmentation. (Jacoby et al., Background). Jacoby et al. teaches that in two patients with more than 3 months follow-up, they observed in vivo mitochondrial enrichment starting 3-4 months after cellular therapy, and throughout the follow-up period (Figure). Metabolic function of PBMCs showed improvement at 5 months post-treatment in lymphocyte ATP content, O2 consumption and TMRE:MTG ratio, indicating improved mitochondrial respiratory capacity. (Jacoby et al., Results). So, Jacoby et al. teaches that their method restores at least some function to a hematopoietic cell, namely improved function of the mitochondria in a subject’s PBMC.
Regarding claim 31, as discussed in MPEP § 2112, citing In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594), the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph). In the instant case, there is reason to believe that Jacoby et al.’s method reduces the need of blood transfusions in at least some cases.
Jacoby et al. does not specify that their subjects had a reduced need for blood transfusions. However, Jacoby et al. does teach that following cell therapy, no events of metabolic crisis occurred, along with normalization of a pre-treatment negative base excess in patient 1 and ongoing improvement in baseline lactate levels in patient 2. Aerobic ability and fine motor functions were superior compared to baseline in both patients. Importantly, quality of life, as measured by the International Pediatric Mitochondrial Disease Score (IPMDS), was greatly improved after treatment.
Farruggia et al. teaches that Pearson Syndrome is characterized principally by a transfusion-dependent anemia that usually improves over time, a tendency to develop severe infections, and a high mortality rate. (Farruggia et al., Abstract). So, blood transfusions are a known treatment for PS, and Farruggia et al. teaches that the frequency of these transfusions may be adjusted according to the needs of the subject.
It is reasonable to assume that an improvement of a number of symptoms after Jacoby et al.’s mitochondrial augmentation therapy may lead in some cases to at least a slight reduction in the need for a blood transfusion. That said, a skilled physician may choose to continue administering transfusions anyway, but an improvement in PS related symptoms may still reasonably reduce the need of other treatments, including blood transfusions, at least to some degree since Jacoby et al.’s augmentation method appears to be successfully treating at least some subjects suffering from PS.
Regarding claim 32, as discussed in MPEP § 2112, citing In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594), the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph). In the instant case, there is reason to believe Jacoby et al.’s augmented HSC (CD34+ by definition) possess improved cell differentiation, since Jacoby et al.’s augmentation method is virtually identical to the claimed method, so Jacoby et al.’s cells would possess the same characteristics of the claimed augmented stem cells, including improved CD34+ erythroid differentiation.
Regarding claim 36, As discussed in MPEP § 2112, citing In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594), the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph). In the instant case, there is reason to believe that Jacoby et al.’s augmented HSC migrated to the bone marrow and established new hematopoietic colonies.
Firstly, Jacoby et al.’s augmentation method is virtually identical to the claimed method, so Jacoby et al.’s cells would possess the same characteristics of the claimed augmented stem cells, including improved CD34+ erythroid differentiation.
In addition, Jacoby et al. introduces their hematopoietic stem cells intravenously. It is known in the art that HSC naturally migrate to the bone marrow in a process called homing. (Magnon et al., “Post-natal HSC migration to bone marrow” section). PBMC of course originate from hematopoietic stem cells, many of which are located in the bone marrow, which further suggests that Jacoby et al.’s augmented HSC treatment resulted in the augmented HSC that generate improved PBMC. So, considering that HSC migrate to bone marrow naturally, it is reasonable to believe that at least some of the HSCs in Jacoby et al.’s method migrated to the bone marrow and colonized it to establish new hematopoietic colonies, generating improved PBMC.
Regarding claim 37, As discussed in MPEP § 2112, citing In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594), the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph). In the instant case, there is reason to believe that Jacoby et al.’s subjects were administered a blood transfusion as part of their treatment method for PS, either before or after mitochondrial augmentation therapy.
Blood transfusions are a commonly known treatment method for PS. (Farrugia). While mitochondrial augmentation may reduce the need for transfusions, a skilled physician would still be motivated to administer a blood transfusions as a part of the known routine treatment methods. The claim language also does not rule out the possibility of administering a blood transfusion before augmentation therapy. According to Farrugia, PS is effectively by definition transfusion-dependent disease, oftentimes from birth. So, it is reasonable to assume that a PS subject, including a PS subject in Jacoby et al., had either received a blood transfusion at some point before the augmentation therapy, or was administered a blood transfusion afterwards as a part of routine treatment for PS.
Allowable Subject Matter
Claims 1-4, 7, 9-11, 15-21, are allowed.
The following is an examiner’s statement of reasons for allowance:
The closest prior art includes the following articles:
Jacoby, Elad, et al. "First-in-human mitochondrial augmentation of hematopoietic stem cells in Pearson syndrome." Blood 132 (2018): 1024. (Provided in IDS of 5/29/2024)
Shin, Myung Geun, et al. "Mitochondrial DNA mutations in patients with myelodysplastic syndromes." Blood, The Journal of the American Society of Hematology 101.8 (2003): 3118-3125. (Provided in IDS of 5/29/2024)
Adès L, Itzykson R, Fenaux P, Myelodysplastic syndromes, The Lancet, 2014; 383, 2239-2252
Filanovsky, Kalman et al. “Peripheral Blood Cell Mitochondrial Dysfunction in Myelodysplastic Syndrome Can Be Improved by a Combination of Coenzyme Q10 and Carnitine.” Mediterranean journal of hematology and infectious diseases vol. 12,1 e2020072. 1 Nov. 2020
Mitochondrial augmentation therapy is known in the prior art and is known to be useful to treat certain mitochondrial diseases. (Jacoby et al.). The motivation to create the cell of claim 1 would reasonably stem from a desire to treat a subject suffering from MDS with the resulting cell. It appears difficult if not impossible to assume that the claimed composition comprising stem cells with augmented mitochondria (and the method of using it to treat a disease) would predictably treat subject suffering from a myelodysplastic syndrome specifically.
It is not clear from the prior art if mitochondrial dysfunction is the sole or even a contributing cause of MDS. Shin teaches that their data do not support a major role for mitochondrial genomic instability in myelodysplasia, and they fail to reproduce previous reports of significant or widespread mitochondrial mutations in this disease. (Shin, Abstract). Ades teaches that the cause of myelodysplastic syndromes is known in only 15% of cases. Further, Ades, which is a comprehensive review article of Myelodysplastic syndromes, does not mention defective mitochondria (Ades, pg 2239). Filanovsky does recognize that structural mitochondrial abnormalities and genetic aberrations in mitochondrial proteins have been known in Myelodysplastic syndrome (MDS) (Filanovsky, Abstract). However, Filanovsky instead seeks to treat the disorder with food supplements, and does not suggest the augmentation of mitochondria to treat the disorder. (Filanovsky, Abstract).
There does not appear to be any motivation in the art to attempt this treatment for MDS, and thus no motivation to create the claimed augmented stem cell pharmaceutical composition.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee. Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”
Conclusion
Claims 1-4, 7, 9-11, 15-21, are allowed.
Claims 23, 30-32, and 36-37 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to THOMAS RUSSE AMICK whose telephone number is (571)272-5474. The examiner can normally be reached 7:30-5 M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Tracy Vivlemore can be reached at (571) 272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/THOMAS R. AMICK/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
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