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 1-21 and 41-100 have been cancelled.
Claims 21-40 are pending and under current examination.
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 21-40 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 21 recites the preamble “a method”. This is indefinite because it is unclear what the method is used for. That is, applicant describes one thing in the specification but claims another. Thus, applicant fails to claim what they regard as the invention as required under 112(b). Amending the claim to indicate the purpose of the method would obviate the rejection.
Claim 21 recites “an effective amount”; however, neither the remaining text of the claim nor the specification provide definitive guidance as to what the amount is effective for, therefore the amount of chlorite salt that must be administered in methods falling within the scope of the invention is unclear and the claim is indefinite.
Claim 22 recites “at least six months after the administering”. This phrase renders the claim indefinite because there is no upper limit on duration between administering the chlorite salt and the measurement of telomere length in a stem cell. As such, one having ordinary skill cannot unambiguously ascertain the meets and bounds of the claim.
The term “substantially ” in claim 28 is a relative term which renders the claim indefinite. The term “substantially” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. As such the amount of preservative permitted is unclear and the claim is indefinite.
Claim 36 recites “in each following month”. This renders the claim indefinite because there is no upper limit on the duration for which the chlorite salt is administered.
Claims 37 and 38 both recite “about every day”. This renders the claim indefinite because it is unclear what time frame is embraced by the phrase.
Claim 40 recites “providing additional administrations of the chlorite salt to the subject based at least in part on the telomere length”. This language is indefinite because it requires a conditional active step of providing additional administrations without clearly identifying the conditions under which the active step must be taken or avoided.
Claims depending from rejected claims have also been rejected because they incorporate all of the limitations of the claims from which they depend, but fail to resolve the indefiniteness concerns outlined above.
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.
Claims 21-40 are rejected under 35 U.S.C. 103 as being unpatentable over McGrath et al. US20170106017; publication date: 04/20/2017; cited in the IDS filed 08/25/2025) in view of Hochstrasser et al. (Experimental Gerontology 47 (2012) 160-163) and further in view of Weng (Current Opinion in Immunology 2012 24:470-475).
With regard to claim 1, McGrath discloses a method of treating conditions impacted by macrophages by administering a chlorite salt and using biomarkers for selection of responders and treatment monitoring (abstract, 0075). McGrath teaches chlorite has been used to treat macrophage-related diseases such as amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) (0003) and the level of one or more biomarker level in the plasma can be measured in the subject during the treatment period. The measured level of biomarker can be subsequently correlated to normal and diseased levels of said biomarker and/or levels of biomarker in said subject prior to treatment (0216). The level of biomarker would typically decrease after treatment (0217). The biomarker is for monitoring inflammation progress and can be a monocyte activation marker (0220).
McGrath does not disclose evaluating telomere length in a stem cell taken from the subject after the administering.
Hochstrasser teaches that shorter telomere length of leukocytes has been linked to age-related conditions including neurodegenerative diseases and Alzheimer’s disease (page 160, left col). Long term chronic inflammation and/or oxidative stress contributes to telomere shortening in monocytes (page 162, right col). Hochstrasser suggests that monocyte telomere length in individual patients may be useful as a biomarker for personalized long-term monitoring of an individual’s health (abstract).
Weng teaches that attrition of telomers occurs during DNA replication [during cell division] and telomere length has been associated with a wide range of health conditions of immune and non-immune cells (abstract). A large body of research has established that intact telomere function is essential for cell proliferation and that impaired telomere maintenance has a severe detrimental impact for cells such as stem cells that rely on proliferation for their function (page 470, right col). There is little question that telomere length can influence bone marrow (i.e. hematopoietic stem cell) function (page 472, left col). Studies of genetic abnormalities associated with telomere impairment demonstrate a critical role of telomeres in proliferation of stem cells … thus lymphocytes with short telomeres will have a reduced ability to mount a strong and sustained immune response (page 473, right col).
It would have been prima facie obvious to measure telomere length in a stem cell, specifically a hematopoietic stem cell, as one of the biomarkers to test for response in McGrath’s method. The artisan of ordinary skill would have been motivated to do so as an assessment of improvement in the health of the immune system after chlorite treatment. The skilled artisan would have had reasonable expectation of success because this would merely require collecting the cells from the patients and testing for telomere length, and both Hochstrasser and Weng establish that methods for this were known as of the instant effective filing date.
With regard to claim 22, in McGrath’s examples efficacy was measured after 6 months of treatment therefore it would have been obvious to also test telomere length at this time.
With regard to claim 23, the chlorite source may be sodium chlorite (0140).
With regard to claims 24-27, McGrath teaches a chlorite dosing regimen (0148), of chlorite in a pharmaceutically acceptable carrier (0062), having a pH of about 7.0 to about 8.0 (0099), and sodium phosphate dibasic (0140).
With regard to claim 28, the concentration of chlorite may be 62 mM (0097).
With regard to claims 30 and 35, McGrath discloses administering between 1 - 2 mg/kg subject body mass of the chlorite salt (claim 23; limitation of instant claim 35) and discloses e.g. a 5.6 mg/mL sodium chlorite solution (0140). It would have been merely routine for one of ordinary skill to determine the volume required to reach a target dose for a given individual, based upon their mass. For this reason, the examiner does not consider the volume required by instant claim 30 to patentably define over the cited prior art.
With regard to claims 31-34, oral or parenteral administration (0145) and in examples the chlorite salt is infused over a time period of 30 min (0224).
With regard to claims 36 and 38, in an example method, McGrath discloses Cycle 1/Week 1 consisted of 5 consecutive daily (i.e. “about every day”) infusions. Cycles 2, 3, 4, 5, and 6 ( Weeks 5, 9, 13, 17, and 21, respectively) each consisted of 3 consecutive daily infusions (0224).
With regard to claim 37, McGrath teaches that the dosing schedule consists of periods of administration alternating with periods of non-administration (0154). This would give one of ordinary skill, i.e. an individual with an advanced degree in medicine such as an M.D. or a Ph.D. a starting point to optimize the dosing regimen for tolerability and efficacy.
Instant claim 39 recites an intended outcome that the examiner considers inherent in carrying out the method rendered obvious by McGrath, Hochstrasser, and Weng because the instant specification indicates that administration of the chlorite salt formulation disclosed by McGrath has the effect of enhancing telomere length over values for this marker observed without chlorite salt administration.
With regard to claim 40, McGrath teaches assessing response by measuring biomarkers of monocyte activation and Hochstrasser and Wang render obvious evaluating response to treatment by assessment of telomere length in McGrath’s method. It would have been prima facie obvious to factor in improvement in telomere length of stem cells as another biomarker of response, and provide additional administration to those who respond to treatment.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 21-40 are rejected on the ground of nonstatutory double patenting as being unpatentable over
claims 1-12 of U.S. Patent No. 11938147 (cited in the IDS filed 08/25/2025);
claims 1-20 of U.S. Patent No. 11938149 (cited in the IDS filed 08/25/2025);
claims 1-20 of U.S. Patent No. 11938150 (cited in the IDS filed 08/25/2025);
claims 1-14 of U.S. Patent No. 12109228 (cited in the IDS filed 08/25/2025);
claims 1-14 of U.S. Patent No. 12109229 (cited in the IDS filed 08/25/2025);
claims 1-20 of U.S. Patent No. 12109230 (cited in the IDS filed 08/25/2025);
claims 1-20 of U.S. Patent No. 12109231 (cited in the IDS filed 08/25/2025);
claims 1-18 of U.S. Patent No. 12233086 (cited in the IDS filed 08/25/2025);
claims 1-11 of U.S. Patent No. 12329776 (cited in the IDS filed 08/25/2025);
claims 1-9 of U.S. Patent No. 9364501 (cited in the IDS filed 08/25/2025);
in view of Hochstrasser et al. (Experimental Gerontology 47 (2012) 160-163) and further in view of Weng (Current Opinion in Immunology 2012 24:470-475).
Inter alia the claims of the cited patents embrace a method of administering a sodium chlorite containing composition followed by measurement of a biomarker to treat a neurodegenerative disease, amyotrophic lateral sclerosis (ALS) or dementia.
The claims of the cited patents do not measure telomere length in a stem cell after the sodium chlorite administration step.
Hochstrasser teaches that shorter telomere length of leukocytes has been linked to age-related conditions including neurodegenerative diseases and Alzheimer’s disease (page 160, left col). Long term chronic inflammation and/or oxidative stress contributes to telomere shortening in monocytes (page 162, right col). Hochstrasser suggests that monocyte telomere length in individual patients may be useful as a biomarker for personalized long-term monitoring of an individual’s health (abstract).
Weng teaches that attrition of telomers occurs during DNA replication [for cell division] and telomere length has been associated with a wide range of health conditions of immune and non-immune cells (abstract). A large body of research has established that intact telomere function is essential for cell proliferation and that impaired telomere maintenance has a severe detrimental impact for cells such as stem cells that rely on proliferation for their function (page 470, right col). There is little question that telomere length can influence bone marrow (i.e. hematopoietic stem cell) function (page 472, left col). Studies of genetic abnormalities associated with telomere impairment demonstrate a critical role of telomeres in proliferation of stem cells … thus lymphocytes with short telomeres will have a reduced ability to mount a strong and sustained immune response (page 473, right col).
It would have been prima facie obvious to measure telomere length in a stem cell, specifically a hematopoietic stem cell, as one of the biomarkers to test for response in the methods embraced by the cited patents. The artisan of ordinary skill would have been motivated to do so as an assessment of improvement in the health of the immune system after chlorite treatment. The skilled artisan would have had reasonable expectation of success because this would merely require collecting the cells from the patients and testing for telomere length, and both Hochstrasser and Weng establish that methods for this were known as of the instant effective filing date.
Claims 21-40 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 46-59 of copending Application No. 18002385 in view of Hochstrasser et al. (Experimental Gerontology 47 (2012) 160-163) and further in view of Weng (Current Opinion in Immunology 2012 24:470-475).
Inter alia the claims of the cited application embrace a method of administering a sodium chlorite containing composition followed by measurement of a biomarker to treat a neurodegenerative disease, amyotrophic lateral sclerosis (ALS).
The claims of the cited patents do not measure telomere length in a stem cell after the sodium chlorite administration step.
Hochstrasser teaches that shorter telomere length of leukocytes has been linked to age-related conditions including neurodegenerative diseases and Alzheimer’s disease (page 160, left col). Long term chronic inflammation and/or oxidative stress contributes to telomere shortening in monocytes (page 162, right col). Hochstrasser suggests that monocyte telomere length in individual patients may be useful as a biomarker for personalized long-term monitoring of an individual’s health (abstract).
Weng teaches that attrition of telomers occurs during DNA replication [for cell division] and telomere length has been associated with a wide range of health conditions of immune and non-immune cells (abstract). A large body of research has established that intact telomere function is essential for cell proliferation and that impaired telomere maintenance has a severe detrimental impact for cells such as stem cells that rely on proliferation for their function (page 470, right col). There is little question that telomere length can influence bone marrow (i.e. hematopoietic stem cell) function (page 472, left col). Studies of genetic abnormalities associated with telomere impairment demonstrate a critical role of telomeres in proliferation of stem cells … thus lymphocytes with short telomeres will have a reduced ability to mount a strong and sustained immune response (page 473, right col).
It would have been prima facie obvious to measure telomere length in a stem cell, specifically a hematopoietic stem cell, as one of the biomarkers to test for response in the methods embraced by the cited application. The artisan of ordinary skill would have been motivated to do so as an assessment of improvement in the health of the immune system after chlorite treatment. The skilled artisan would have had reasonable expectation of success because this would merely require collecting the cells from the patients and testing for telomere length, and both Hochstrasser and Weng establish that methods for this were known as of the instant effective filing date.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE PEEBLES whose telephone number is (571)272-6247. The examiner can normally be reached Monday through Friday: 9 am to 3 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ali Soroush can be reached at (571)272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KATHERINE PEEBLES/Primary Examiner, Art Unit 1617
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