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 .
Election/Restrictions
Applicant's election with traverse of Group II, claims 4, 5, and 7-15, in the reply filed on 03/25/2026 is acknowledged. The traversal is on the ground(s) that applicant has define the “actual special technical feature shared by Groups I and II is the use of a urolithin for increasing long term stem cell function for at least 40 weeks. This is not found persuasive because the limitation recited by applicant is a result of practicing the method step of contacting a population of HSPCs with urolithin which is explicitly taught by Girotra, employed in the restriction requirement. Thus the result of increased long term stem cell function for at least 40 weeks is inherently met by Girotra.
The requirement is still deemed proper and is therefore made FINAL.
Claims 2-3 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected group, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 03/25/2026.
Status of the Claims
Claims 2-5 and 7-15 are currently pending.
Claims 3-5 and 7-15 are amended.
Claims 2-3 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.
Claims 1 and 6 are cancelled.
Claims 4-5 and 7-15 have been considered on the merits.
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 4, 7-10, and 12-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 5, 8, and 10-11 of copending Application No. 17423718 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because claim 4 of the instant application is generic to all that is recited in claim 1 of ‘718.
Specifically, claim 4 of the instant application is drawn to a method for increasing stem cell function in HSPCs in a subject through the active step of “administering urolithin to the subject”. Additionally, claim 4 recites the intended result of “wherein the stem cell function is increased for at least 40 weeks”, which is interpreted to be an intended result of practicing the method of administering urolithin because no additional steps are recited to achieve this outcome. The only active step in claim 4 is the step of “administering urolithin to the subject”.
In the reference application, ‘718, claim 1 recites a method of increasing engraftment in a population of HSPCs with the active step of “administering an effective amount of urolithin to the subject”, thus fully encompassing the method of claim 4 of the instant application.
Claim 7 of the instant application requires wherein the method of therapy is treatment or prevention of a disease selected from the group consisting of anemia, leukopenia, thrombocytopenia, an infection, and cancer; which is encompassed by claim 10 of ‘718.
Claim 8 of the instant application requires wherein the stem cell function comprises one or more of capacity for engraftment, self-renewal, and blood or immune cell differentiation; which is encompassed by claim 1 of ‘718.
Claim 9 of the instant application requires wherein the increased stem cell function increases blood cell levels in the subject; which is encompassed by claim 5 of ‘718.
Instant claim 10 requires that the urolithin is urolithin A; which is encompassed by claim 2 of ‘718.
Claim 12 of the instant application requires wherein the urolithin is in the form of a pharmaceutical or nutritional composition; which is encompassed by claim 8 of ‘718.
Instant claim 13 requires wherein the subject has or is at risk of having subnormal amounts of hematopoietic cells; which is encompassed by claim 1 of ‘718.
Instant claim 14 requires wherein the subject has or is at risk of having anemia, leukopenia and/or thrombocytopenia; which is encompassed by claim 10 of ‘718.
Claim 15 of the instant application requires wherein the subject has undergone an intervention selected from the group consisting of a hematopoietic stem cell transplant, a bone marrow transplant, myeloablative conditioning, chemotherapy, radiotherapy, and surgery; which is encompassed by claim 11 of ‘718.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 4, 7, 10, and 14-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8, 9, 12 of copending Application No. 18246744 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because claim 4 of the instant application is generic to all that is recited in claim 8 of ‘744.
Specifically, claim 4 of the instant application is drawn to a method for increasing stem cell function in HSPCs in a subject through the active step of “administering urolithin to the subject”. Additionally, claim 4 recites the intended result of “wherein the stem cell function is increased for at least 40 weeks”, which is interpreted to be an intended result of practicing the method of administering urolithin because no additional steps are recited to achieve this outcome. The only active step in claim 4 is the step of “administering urolithin to the subject”.
In the reference application, ‘744, claim 8 recites a method of treating anemia, leukopenia, and/or thrombocytopenia, an infection, or an hematological cancer comprising the active step of “administering to the subject a composition comprising a combination of a urolithin…” thus fully encompassing the method of claim 4 of the instant application.
Claim 7 of the instant application requires wherein the method of therapy is treatment or prevention of a disease selected from the group consisting of anemia, leukopenia, thrombocytopenia, an infection, and cancer; which is encompassed by claim 8 of ‘744.
Instant claim 10 requires that the urolithin is urolithin A; which is encompassed by claim 9 of ‘744.
Claim 12 of the instant application requires wherein the urolithin is in the form of a pharmaceutical or nutritional composition; which is encompassed by claim 12 of ‘744.
Instant claim 14 requires wherein the subject has or is at risk of having anemia, leukopenia and/or thrombocytopenia; which is encompassed by claim 8 of ‘74.
Claim 15 of the instant application requires wherein the subject has undergone an intervention selected from the group consisting of a hematopoietic stem cell transplant, a bone marrow transplant, myeloablative conditioning, chemotherapy, radiotherapy, and surgery; which is encompassed by claim 8 of ‘744.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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 5 and 11 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 5 recites the limitation “ wherein the method comprises contacting the HSPCs with the urolithin prior to administration of the HSPCs to a subject”, which is indefinite. Claim 5 depends from claim 4 which recites “wherein the stem cell function is increased for at least 40 weeks comprising administering urolithin to the subject”. Thus, the independent claim 4 establishes that the subject of this method is being administered urolithin directly and nowhere are HPSCs being administered to the subject within the method of claim 4. Claim 5 attempts to limit claim 4 to contacting HSPCs with urolithin outside of the subject which appears to be an entirely different method than that of independent claim 4 rendering claim 5 unclear. It is also unclear if applicants intended for HPSCs from a subject to be contacted with urolithin and the subject is then administered the urolithin contacted HSPCs in addition to directly administering urolithin into the subject. Appropriate clarification is required.
Claim 5 recites the limitation "administration of the HSPCs" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 11 recites the limitation "the population or sub-population" in lines 2-3. There is insufficient antecedent basis for this limitation in the claim.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 4-5 and 7-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Girotra et al (WO2020148445A1, published 07/23/2020 and filled 01/17/2020).
The applied reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
With regards to claim 4, Girotra teaches a method for increasing stem cell function in hematopoietic stem and/or progenitor cells (HSPCs) in a subject (pg. 3, lines 13-14), wherein the stem cell function is increased at the 24th week comprising administering urolithin to the subject (pg. 7, lines 16-29; pg. 3, lines 13-14).
With regards to claim 5, Girotra teaches that the method comprises contacting the HSPCs with urolithin prior to administration of the HPSCs to a subject (pg. 4, lines 9-21.
Regarding claim 7, Girotra teaches wherein the method of therapy is treatment of prevention of anemia, leukopenia, and/or thrombocytopenia, infection, or cancer (pg. 3, lines 1-3).
Regarding claim 8, Girotra teaches wherein the stem cell function comprises capacity for engraftment, self-renewal, and blood or immune cell differentiation (pg. 2, lines 6-7 and 11-12).
Regarding claim 9, Girotra teaches wherein the increased stem cell function increases blood cell levels in the subject because Girotra describes that subjects injected with UroA-cultured cells show higher blood reconstitution over a period of 24 weeks (pg. 7, lines 16-29).
Regarding claim 10, Girotra teaches that the urolithin is urolithin A (pg. 3, line 12).
Regarding claim 11, Girotra teaches wherein the population of subpopulation of HSPCs is contacted with urolithin for up to and including 7 days (pg. 7, lines 6-15) .
Regarding claim 12, Girotra teaches wherein the urolithin is in the form of a pharmaceutical or nutritional composition (pg. 3, lines 15-16).
Regarding claim 13, Girotra teaches wherein the subject has or is at risk of having subnormal amounts of hematopoietic cells (pg. 3, lines 20-21).
Regarding claim 14, Girotra teaches wherein the subject has or is at risk of having anemia, leukopenia, and/or thrombocytopenia (pg. 3, lines 1-3).
Regarding claim 15, Girotra teaches wherein the subject has undergone an intervention of hematopoietic stem cell transplant, bone marrow transplant, myeloablative conditioning, chemotherapy, radiotherapy, and surgery (pg. 3, lines 24-26).
Claim 4 contains a wherein clause that recites the intended result of the method rather than requiring an additional step be performed. Claim 4 recites “wherein the stem cell function is increased for at least 40 weeks”. The art teaches increased stem cell function at the 24th week but does not provide testing up until week 40. MPEP 2111.04 states “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed” and that a such a clause ‘"in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” Therefore since these claims only recite the results of the steps, then art reading on claim 4 will also read on these results since performing the same steps will inherently lead to the same results in the absence of evidence to the contrary including unexpected results.
Therefore, Girotra anticipates the claims.
Claims 4, 7-10, and 12-15 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Singh et al (US20190328703A1, published 10/31/2019).
With regards to claim 4, Singh teaches a method for increasing stem cell function in hematopoietic stem and/or progenitor cells (HSPCs) in a subject (Example 3, [0292]-[0294]), wherein the subject is treated for 34 weeks and the Urolithin A treatment results in a significant increase in hematopoietic stem cells comprising administering urolithin to the subject (Example 3, [0292]-[0294]).
Regarding claim 7, Singh teaches wherein the method of therapy is treatment or prevention of infection or cancer ([0114]/[0126]).
Regarding claim 8, Singh teaches wherein the stem cell function comprises self-renewal and blood or immune cell differentiation (Example 3 and [0131]).
Regarding claim 9, Singh teaches wherein the increased stem cell function increases blood cell levels in the subject because Singh describes that subjects injected with UroA demonstrate blood reconstitution of all of the different blood cell lineage populations ([0294]).
Regarding claim 10, Singh teaches that the urolithin is urolithin A ([0176]).
Regarding claim 12, Singh teaches wherein the urolithin is in the form of a pharmaceutical or nutritional composition ([0242]-[0243]).
Regarding claim 13, Singh teaches wherein the subject has or is at risk of having subnormal amounts of hematopoietic cells ([0130]).
Regarding claim 14, Singh teaches wherein the subject has or is at risk of having leukopenia by teaching that the patient may have leukemia which provides a risk of leukopenia ([0126]).
Regarding claim 15, Singh teaches wherein the subject has undergone an intervention of hematopoietic stem cell transplant, bone marrow transplant ([0012]), chemotherapy ([0126]), and surgery ([0156]).
Claim 4 contains a wherein clause that recites the intended result of the method rather than requiring an additional step be performed. Claim 4 recites “wherein the stem cell function is increased for at least 40 weeks”. The art teaches increased stem cell function after administering for a total of 34 weeks. MPEP 2111.04 states “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed” and that a such a clause ‘"in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” Therefore since these claims only recite the results of the steps, then art reading on claim 4 will also read on these results since performing the same steps will inherently lead to the same results in the absence of evidence to the contrary including unexpected results.
Therefore, Singh anticipates the claims.
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.
Claim(s) 4-5 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Singh et al (US20190328703A1, published 10/31/2019), in view of Tajer et al (Cells, 2019, “Ex Vivo Expansion of Hematopoietic Stem Cells for Therapeutic Purposes: Lessons from Development and the Niche”).
With regards to claims 5 and 11, the limitations of the independent claim 4 are taught above.
Singh does not teach that the hematopoietic stem cells are contacted with urolithin prior to administration of the HSPCs to a subject as required by claim 5. Singh does not teach wherein the population or sub-population of HSPCs is contacted with the urolithin for up to and including 7 days as required by claim 11.
Singh does teach that contacting a subject with urolithin increases hematopoietic stem cell populations. Singh states “this increase in the most primitive stem cell population results in an even more pronounced increase in the final total numbers of HSC's present in the hindlimb both as a % of total bone marrow cells, as well as cell numbers, as shown in FIG. 4, with there being a significant increase in HSC cells numbers in aged animals treated with urolithin A versus aged animals that were not treated” ([0294]).
Additionally, Tajer et al teaches about ex vivo expansion of HSC populations and describes this as “a “holy grail” in the field for many years. Ex vivo expansion of HSCs can help to overcome material shortage for transplantation purposes and genetic modification protocols” (abstract). Tajer teaches that one of the main challenges of using HSCs in clinical applications is the limited number of cells that can be enriched from a patient and that expanding HSCs has become an important prerogative in clinical applications (pg. 6, para 3). Tajer also teaches a method of short term proliferation of 4 days with a combination of cytokines which promote HSC proliferation (pg. 6, para 3).
Regarding claim 5, Tajer teaches contacting HSCs with proliferation cocktails prior to administration in clinical applications and Singh provides evidence that urolithin is able to influence HSCs to proliferate, therefore the combination of Singh and Tajer meets the limitations of claim 5 (pg. 6, para 3 of Tajer and [0294] of Singh).
Regarding claim 11, Tajer teaches short term proliferation of HSCs for about 4 days prior to administration (pg. 6, para 3), and Singh provides evidence that urolithin is able to influence HSCs to proliferate, therefore the combination of Singh and Tajer meets the limitations of claim 11 (pg. 6, para 3 of Tajer and [0294] of Singh).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine contacting HSCs with urolithin for in vivo proliferation taught by Singh with HSC expansion/proliferation prior to clinical administration taught by Tajer to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Tajer teaches about ex vivo expansion of HSC populations and describes this as “a “holy grail” in the field for many years. Ex vivo expansion of HSCs can help to overcome material shortage for transplantation purposes and genetic modification protocols” (abstract). Additionally, Tajer teaches that one of the main challenges of using HSCs in clinical applications is the limited number of cells that can be enriched from a patient and that expanding HSCs has become an important prerogative in clinical applications (pg. 6, para 3). Further, Singh teaches that HSCs contacted with urolithin demonstrate increased cell populations in vivo ([0294]). One of ordinary skill in the art would have a reasonable expectation of success when combining Singh with Tajer because both teach the necessary information for a person of ordinary skill in the art to contact HSCs both in vivo and ex vivo.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CONSTANTINA E STAVROU whose telephone number is (571)272-9899. The examiner can normally be reached M-F 8:00-5:00.
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, Peter Paras can be reached at 571-272-4517. 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.
CONSTANTINA E. STAVROU
Examiner
Art Unit 1632
/ANOOP K SINGH/Primary Examiner, Art Unit 1632
Prosecution Insights