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 .
Claim Status
Claims 2-4, 8-9, 11-13, and 16-21 are currently pending in this application.
Election/Restrictions
Applicant’s election without traverse of Group II, claims 8-16, in the reply filed on Nov. 15, 2025 is acknowledged. Claims 2-4 and 17-19 have been withdrawn from consideration as being drawn to non-elected subject matter, and claims 8-9, 11-13, 16, and 20-21 have been considered on the merits.
Previous Rejections
Status of the rejections: the previous rejections under 112(a) are withdrawn in view of the claim amendments, except as specifically maintained below; the previous claim rejections under section 112(b) are withdrawn in view of the claim amendments and remarks; and the previous claim rejections under section 112(d) and 102(a)(1) are withdrawn in view of the claim amendments.
Claim Objections
Claims 8, 11 and 21 are objected to because of the following informalities:
Claims 8 and 11 show an inconsistent use of capitalization in the term “nicotinamide Riboside.”
Claim 21 recites the term “HSC” function, which presumably relies on an abbreviation for “haematopoietic stem cell” function. If this is an abbreviation, then the abbreviation needs to be spelled out at least once. Appropriate correction is required.
Claim Interpretation
In claim 12, the term “pharmaceutical composition” is interpreted under a broadest reasonable claim interpretation as implicitly requiring the composition comprising the combination also comprises at least one additional “pharmaceutical” component to those recited the claim, e.g., water, saline, or other pharmaceutical composition components known in the prior art such as carrier, diluents, excipients, and serum albumins.
Claim Rejections - 35 USC § 112(a), Written Description (modified)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 8-9, 11-13, 16, and 20-21 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Subject in Need of Treatment of an Infection
When claim 8 is analyzed in light of the specification, the instant invention is partly directed to a method comprising administering a composition comprising (1) a urolithin, (2) a specifically recited nicotinamide adenine dinucleotide (NAD+) precursor and (3) vitamin B12 to a subject in need of treatment of an infection. Claim 8 further limits the subjects in need of treatment of an infection to only those subjects also having anemia, leukopenia, and/or thrombocytopenia (e.g., pancytopenia) and/or having undergone at least one of hematopoietic stem cell transplant, bone marrow transplant, myeloablative conditioning, chemotherapy and radiotherapy.
M.P.E.P. §2163 states “To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.”
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described. However the instant application lacks any description of (1) an infected subject having all three of anemia, leukopenia, and thrombocytopenia; or (2) an infected subject having undergone hematopoietic stem cell transplant, bone marrow transplant, myeloablative conditioning, chemotherapy and/or radiotherapy.
In the instant case, the specification describes treating infections or infectious diseases encompasses acute infections, infections of the CNS, and/or non-viral or viral ones, such as by human immune deficiency virus (HIV) or B19 parvovirus and/or symptoms of infection, e.g., rhinitis or ocular inflammation. However it is not clear if any of the aforementioned infected subjects are representatives of subjects having anemia, leukopenia, thrombocytopenia, a hematopoietic stem cell transplant, a bone marrow transplant, and/or undergone myeloablative conditioning, chemotherapy and/or radiotherapy. Furthermore claim 8 or 13 encompasses a single subject having all of the following: anemia, leukopenia, thrombocytopenia, a hematopoietic stem cell transplant, a bone marrow transplant, and undergone myeloablative conditioning, chemotherapy and radiotherapy. But no such representative subject is disclosed in the instant specification or indicated in the prior art as in specifically in need of treatment for an infection.
Instead there is description of patients generally suffering from infections, either viral or non-viral but not regarding any of the recited conditions in claim 8 or 13. In other words, the instant application fails to provide any representative species of a subject having an infection in combination with any of the requisite conditions recited in claim 8 or 13. The prior art does provide a nexus between either HIV or B19 parvovirus infection and anemia, leukopenia, and/or thrombocytopenia as well as procedures like a hematopoietic stem cell or bone marrow transplant and a risk of infections, such as with EBV, CMV, or HSV; however, prevention (i.e., in a subject at risk) has been canceled from the instant claims and, thus, the patient in need of treatment for infection must necessarily be actually afflicted with an infection at the time of administering.
Subject in Need of Treatment of a Hematological Cancer
When claim 8 is analyzed in light of the specification, the instant invention is also directed to a method comprising administering a composition comprising (1) a urolithin, (2) a specifically recited nicotinamide adenine dinucleotide (NAD+) precursor and (3) vitamin B12 to a subject in need of treatment of a haematological cancer wherein the subjects also has anemia, leukopenia, and/or thrombocytopenia (e.g., pancytopenia) and/or has undergone at least one of hematopoietic stem cell transplant, bone marrow transplant, myeloablative conditioning, chemotherapy and radiotherapy. The instant specification is silent as to any representative of this type of hematological cancer subject beyond ones having undergone a hematopoietic stem cell transplant, bone marrow transplant, myeloablative conditioning, chemotherapy and/or radiotherapy which causes subnormal amounts of hematopoietic stem cells ([0207]) but not explicitly the condition of anemia, leukopenia, thrombocytopenia and/or subnormal amounts of erythrocytes, leukocytes, and/or platelets.
The instant specification lacks any description of a hematological cancer subject having all three of anemia, leukopenia, and thrombocytopenia beyond the existence of risks caused by the medical interventions above, such systemic radio- and/or chemo-therapy. While the prior art teaches certain hematological cancer subjects having lymphoma or multiple myeloma do not have anemia, leukopenia, and/or thrombocytopenia (e.g., localized to lymph nodes or extranodal sites; early active multiple myeloma or solitary plasmacytoma), including after chemotherapy and bone marrow transplant (Conlan et al., Cancer 67(5): 1389-95 (1991) at abstract; Pham, Curr Hematol Malig Rep. 14(2): 63-69 (2019) at Table 1; Prakash et al., Cureus 12(5): e8357 (2020) at pg. 1, last para.). Similarly, radiotherapy can be localized or targeted by antibodies and avoid causing any significant reductions in HSC/bone marrow cell reproduction, indicating any nexus is not generalize to all radiotherapies for a blood cancer.
In the instant case, claim 8 or 13 broadly comprises a genus of haematolgical cancer subjects having leukaemia, lymphoma, myeloma, or a myelodysplastic syndrome ([0208]-[0209], [0178]); however there is no clear nexus described in the specification between these cancers and all of these conditions. Rather the instant application describes subjects having undergone the medical intervention of chemotherapy or radiation therapy (e.g., during a HSC/bone marrow transplant) are at risk of developing subnormal blood cell counts ([0204]-[0209]) but not necessarily in need of treatment just due to having any hematological cancer, or even specifically any leukemia, lymphoma, myeloma, or a myelodysplastic syndrome thereof. Similarly, the description describes subjects having a myelodysplastic syndrome as at risk of developing a decrease in blood levels, but it is not clear if the myelodysplastic syndrome described here is a hematological cancer (categorized instead as autoimmune disorder) and what blood cell specifically is decreased ([0204]).
The instant specification is silent as to any representative of this type of cancer subject beyond blood cancer subjects determined after the intervention to have developed anemia, leukopenia, and/or thrombocytopenia, which fits into category (a) of the preamble of claim 1 making alternative category (c) of the preamble redundant. Instead there is description of patients generally suffering from hematological cancers needing treatment when what needs treatment instead appears to be the anemia, leukopenia, and/or thrombocytopenia. In other words, the instant application fails to provide any representative species of a subject having cancer being treated in the absence of a medical intervention comprising myeloablative condition, chemotherapy or radiotherapy. As neither the instant application nor the prior art does provide a nexus between treating hematologic cancers and administering urolithin, NAD+ precursor, and Vitamin B12, the supported treatment is for subjects with anemia, leukopenia, thrombocytopenia, and/or subnormal amounts of erythrocytes, leukocytes, and/or platelets regardless of whether they had any infection or cancer and regardless of whether the cause was a specific viral infection, hematologic cancer, and/or medical intervention (e.g., myeloablative condition, chemotherapy and/or radiotherapy). Note, prevention (i.e., in a subject at risk) has been canceled from the instant claims and, thus, the patient in need of treatment for anemia, leukopenia, and thrombocytopenia must necessarily be actually afflicted with such at the time of administering, not merely at risk due to having a hematological cancer or having undergone one or more of the medical interventions recited in claim 8.
Thus, the skilled artisan cannot envision the entire genus of subjects from the instant description, which may include subjects having virtually any type of infection without limit or any hematological cancer without limit. Therefore, the skilled artisan cannot envision how to identify which subjects are in need of infection or hematological cancer treatment as encompassed by claim 8 or 13. In conclusion, there is a lack of evidence in the instant specification as filed that the inventors were in possession of a method for use in treatment over the entire scope of the genus of subjects encompassed by claim 8 or 13.
Response to arguments
Applicant’s arguments filed 5/22/26 regarding the 112(a)-WD rejections (pg. 5-6) have been fully considered and found persuasive regarding the previous rejections except as regarding treatment of an infection or haematological cancer in the recited patient stratifications as set forth above. As the “and/or” between the (i) condition(s) and the (ii) intervention(s) in claim 1 means the method encompasses subjects having only (b) infection or (c) hematological cancer and at least one of the interventions but lacking each of anemia, leukopenia and thrombocytopenia; claim 1 as written can treat any infection or hematological cancer in a subject having undergone at least one of the interventions at any previous time in their life (e.g., 10 years prior).
As argued in the response, a common denominator unifying all the subject types of claim 8 (disparate patient stratifications) is the dysfunctional/depressed HSC population in the subject while the composition comprising the three active agents positive effects on HSC cells provides a common utility throughout. However this does not appear to be correct over the full scope of the claims as detailed above. Not every infected subject or hematological cancer subject that has also undergone a specific intervention recited necessarily suffers from a lack of HSCs or dysfunctional production of differentiated blood cells from the HSC population. Rather, the claimed method appears best designed purely for treating a subject with anemia, leukopenia and/or thrombocytopenia regardless of whether this condition is related to an infection, hematological cancer, and/or medical intervention, such as due to a HSC transplant procedure.
35 USC § 112(a), Scope of Enablement (modified)
Claims 8-9, 12-13, 16, and 20-21 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because while enabled wherein the NAD+ precursor comprises NR and/or NMN and the method treats anemia, leukopenia, and/or thrombocytopenia or a hematological cancer/infection causing the aforementioned, the specification does not enable any person, skilled in the art to which it pertains or with which it is most nearly connected to, to make/use the method of claim 8 over its entire scope.
Enablement is considered in view of the Wands factors (MPEP 2164.01 (a)). The court in Wands states that "Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is 'undue.' Not 'experimentation;" (Wands, 8 USPQ2d 104). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighting many factual considerations." (Wands, 8 USPQ2d 1404).
The factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation required is “undue” include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Furthermore, the USPTO does not have laboratory facilities to test if an invention will function as claimed when working examples are not disclosed in the specification. Therefore, enablement issues are raised and discussed based on the state of knowledge pertinent to an art at the time of the invention. And thus, skepticism raised in the enablement rejections are those raised in the art by artisans of expertise.
All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Breadth of the claims:
The claims are broadly directed to methods of treating in a subject (a) anemia, leukopenia and/or thrombocytopenia; (b) infection; or (c) hematological cancer using the administering one or more of any recited NAD+ precursor(s): nicotinic acid, nicotinamide, nicotinamide riboside (NR), reduced nicotinamide riboside (NRH), nicotinamide mononucleotide (NMN), nicotinic acid mononucleotide, and nicotinic acid riboside.
The state of the art:
The prior art teaches a NAD+-boosting strategy comprising orally administering (feeding) a NAD+ precursor (vitamin B3 analog, e.g., NMN) to a subject improves HSC function/proliferation in vivo after transplantation thereby increasing populations of white blood cells, monocytes, granulocytes, platelets and neutrophils, especially the NAD+ precursor nicotinamide riboside (NR) in Niagen® (Abstract, Fig. 1, 3, 7; pg. 406, right col., last para., to pg. 407, left col., last para.; pg. 414, left col., last para., to right col.). The art teaches administering to a subject urolithin A can produce an anti-inflammatory effects in vivo and other promising anticancer-related effects in vitro or in combination of with chemotherapeutic agents preclinical animals models, however urolithins have not yet realized its full potential and to treat an infection or cancer on their own, especially in a human subject (see e.g., Karumuru et al., pg. 123, left col., last para., to pg. 134, left col., last para.; Table I). The prior art teaches vitamin B12 supplementation can help treat some viral infections in certain subjects in combination with other agents. It is noted that the prior art teaches HIV, hepatitis, EBV, CMV parvovirus, or B19 can cause pancytopenia which encompasses subnormal amounts of erythrocytes, leukocytes, and platelets as recited as a subject type in claim 13 and also that some leukemia, lymphoma, multiple myeloma, and myelofibrosis and metastatic cancers that infiltrate the bone marrow can cause pancytopenia as recited as a subject type in claim 13.
Thus, the claimed aspects over the scope of the entire genus of disorders recited in claim 8 must be shown to a reasonable extent so that one of the ordinary skills in the art would be able to practice the invention without any undue burden being on such an artisan.
The amount of direction and guidance and working examples provided by Applicant:
Nowhere does the specification provide any working embodiment of administering any composition to a subject nor accomplishing treatment of any condition in a subject. Instead, the only empirical data shown is in vitro data showing the effect of contacting mouse hematopoietic stem cells (HSC) with a composition comprising urolithin A, nicotinamide riboside (NR) and vitamin B12 (Example 1; FIG. 1), which is neither predictive or even instructive of what would happen if the same was administered in vivo to a subject, including a mouse. Similarly, nowhere does the specification provide any example of a method of preventing any type of anemia, leukopenia, thrombocytopenia, infection, or hematologic cancer, not to mention preventing combinations thereof in a single subject, and the in vitro data regarding HSC mitochondria provides no prediction regarding in vivo blood cell levels nor effects on any infection.
Instead, the specification merely demonstrates the combination of urolithin A, nicotinamide riboside (NR) and vitamin B12 (with additional repeated administrations with NR) lowers the mitochondrial membrane potential of mouse bone marrow-derived HSCs. Further, the instant specification provides no direction, guidance or working examples for determining a suitable subject, a suitable route of administration, or a suitable amount to administer to effectuate such a treatment, e.g., via a food, nutraceutical, nutritional supplement, and/or food replacement composition.
In summary, the claims are rejected under 35 U.S.C. 112(a) because the specification does not reasonably provide enablement to a person skilled in the art to which it pertains or with which it is most nearly connected to treat (a) anemia, leukopenia and/or thrombocytopenia; (b) infection; and/or (c) hematologic cancer in any subject via any route of administration of an unrecited amount of the combination of agents. Given the lack of working examples, the limited guidance provided in the specification, the lack of guidance in the prior art, and the broad scope of the claims, undue and/or unreasonable experimentation would have been required for one skilled in the art to produce the desired effect over the full scope of the claims.
Response to arguments
Applicant’s arguments filed 5/22/26 regarding the previous 112(a) rejections (pg. 6-9) have been fully considered and found persuasive regarding the previous rejections except as regarding the breadth of any such subject having any infection or hematological cancer and the full scope of NAD+ precursors as set forth above. The empirical data regarding working embodiments in Fig. 1 is limited to a single NAD+ precursor, nicotinamide riboside (NR) and the evidence is limited to in vitro cell experiments, which is not necessarily indicative of bioactive agents administered to a subject via a food or nutritional supplement where reaching the blood cells, at least in required amounts, could pose a challenge.
Despite applicant’s arguments to the contrary at pg. 9 and 12, not all the claimed conditions are necessarily tied to the condition of a stressed hematological system in the subject. Furthermore, there is no timie limit as to when the subject underwent the prior intervention. Thus, while treating specific hematological conditions are enabled (anemia, leukopenia, and/or thrombocytopenia) with a composition comprising nicotinamide riboside, treating any hematological cancer or infection is not.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 21 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 21 further recites only results of performing the method of claim 8 without reciting an additional method step or limitation to the method steps of claim 8. As it is not clear the language of claim 21 implies any limitation to claim 8 except possibly a hint for determining an effective amount of urolithin, NAD+ precursor, and/or Vitamin B12 to administer or discover by experiment/optimization. Intended use language in a method claim is not limiting if failing to provide or imply any additional active method step or narrowing of a step of the claimed method of the claim from which it depends. Thus, claim 21 fails to further limit the subject matter of a claim 8 in absence of evidence to the contrary. To the extent any of these results/mechanism are argued to be absent from every species of claim 8, then the active steps as recited in claim 21 lack sufficient detail to ensure the said results would predictably occur by performing the method indicating a lack of written description/enablement.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 8-9, 11-13, 16, and 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Andreux (WO2017109195A1) in view of Vannini (US20170252362A1).
Regarding claims 8 and 11, Andreux teaches administering to a subject with cancer a composition comprising nicotinamide riboside (NR), a urolithin, and vitamin B12 (pg. 10, lines 26-31; pg. 4, line 15, to pg. 5, line 16; pg. 4, line 10) to treat the cancer (pg. 20, line 28, to pg. 21, line 15).
Andreux does not teach wherein the cancer is a hematological cancer and the subject either (1) has anaemia, leukopneia or thrombocytopenia and/or (2) has undergone any of the medical interventions recited in claim 8.
However Vannini teaches a method of treating a decreased blood cell level in a subject (e.g., suffering from anemia or a myelodysplastic blood cancer, and/or anemia or thrombocytopenia after chemotherapy for solid cancer or due to B19 or parvovirus infection ([0049])) comprising administering an effective amount of the NAD+ precursor nicotinamide riboside (NR) ([0089]) as mitochondrial membrane potential reducing agent to the subject by injecting or as a food supplement ([0084], [0086], [0092], [0132]; FIG. 5-12). Vannini teaches that the condition of decreased blood cell level can be due to, inter alia, dysfunctional hematopoiesis ([0120], [0132], e.g., inherited anemia) as well as resulting from a hematopoietic stem cell transplant intervention performed on the subject (HSC post-transplanted subject) or bone marrow transplant patient ([0124], [0205], [0013], [0015], [0006]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective time of filing to perform a method of Andreux on a cancer subject wherein when such a subject specifically suffers from anemia and/or thrombocytopenia to administer via injection the composition taught by Andreux to improve hematopoiesis and mitochondrial membrane potentials as taught by Vannini. One of ordinary skill in the art with the goal of benefiting cancer patients afflicted with anemia and/or thrombocytopenia would be motivated by Vannini teaching the NR already in the composition of Andreux can be used in amounts the treat low blood cell counts despite Andreux merely motivating their method to treating cancers generally. Furthermore, Andreux teaches using their composition specifically to increase the number of hematopoietic stem cells and their progeny (e.g., by stimulating mitophagy and autophagy therein) (pg. 22, lines 6-8).
Alternatively, it would have been prima facie obvious to one of ordinary skill in the art before the effective time of filing to perform a composition administering method of Andreux on a subject specifically suffering from anemia and/or thrombocytopenia caused by chemotherapy for solid cancer, HSC transplantation, or B19 or parvovirus infection because Vannini teaches the nicotinamide riboside (NR) in Andreux composition can improve hematopoiesis and blood cell levels. One of ordinary skill in the art with the goal of benefiting subjects afflicted with anemia and/or thrombocytopenia would be motivated by Vannini teaching the NR can improve low blood cell counts in subjects generally regardless of causation. Furthermore, Andreux teaches using the composition specifically to increase the number of hematopoietic stem cells and their progeny (e.g., by stimulating mitophagy and autophagy therein) (pg. 22, lines 6-8).
Regarding claim 9, Andreux teaches wherein the urolithin is urolithin A (abstract; pg. 5, lines 13-14).
Regarding claim 12, Andreux discloses wherein the composition is in the form of a pharmaceutical composition or nutritional composition (pg. 7, line 23).
Regarding claim 13, the anemia or thrombocytopenia conditions taught by Vannini overlaps with conditions of “subnormal” amounts of erythrocytes or platelets. Note, a prima facie case of obviousness exists when the claimed range overlap with what is taught in the prior art. MPEP 2144.05.
Regarding claim 16, as it is unclear what limitation, if any, on the method comes from the language of “combined for separate or sequential use with a G-CSF analogue, thus claim 16 is obvious in view of Andreux and Vannini for the same reasons as set forth above for claim 8.
Regarding claim 20, Andreux discloses wherein the composition is in the form of a pharmaceutical composition or nutritional composition (pg. 7, line 23).
Regarding claim 21, ameliorating HSC function via modulation of mitochondrial membrane potential through mitophagy induction in a recipient subject is considered an inherent result of performing the method as positively recited regardless of intentions based on the logic of the claim is drafted. To the extent any of these results/mechanism are argued to be absent from every species of claim 8, then the active steps as recited in claim 21 lack sufficient detail to ensure the said effects/results would predictably occur by performing the method thereby indicating a lack of written description/enablement.
Therefore the claimed invention as a whole is prima facie obvious before the earliest effective filing date in the absence of evidence to the contrary.
Response to arguments
Applicant’s arguments filed 5/22/26 regarding the previous 103 rejections have been fully considered and found persuasive; however applicant's amendment necessitated the new grounds of obviousness rejections presented above.
Applicant argues Andreux teaches different intentions than the claimed invention, namely increasing mitochondrial respiration capacity/totals as well as increasing mitochondrial biogenesis and respiratory capacity in muscle cells, instead of anaemia, leukopenia or thrombocytopenia, infection and/or haematological cancer, such as after HSC transplant, chemotherapy and/or radiotherapy.
Despite applicant’s arguments at pg. 10-12, the combination of Andreux and Vannini need not appreciate any specific effect at the HSC level to improve HSC stem cell function and/or alleviate an aberrant hematological system, such as via any specific mechanism like improving HSC stemness, self-renewal, engraftment into a bone marrow niche or propensity to differentiate.
Double Patenting (modified)
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 8-9, 11-13, and 20-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2, 18, and 21-26 of the “reference application” US 17/442,217.
Claim 2 of the reference application is directed to a method of treating an infection or hematological cancer in a subject by administering an effective amount of a composition comprising c) the NAD+ precursor nicotinamide riboside (NR), a urolithin, and a Vitamin B12, such as in an immunocompromised subject or subject that has undergone chemotherapy or radiotherapy (claim 25-26); and claim 18 teaches wherein the composition comprises a pharmaceutical carrier, diluent or excipient.
Regarding instant claim 9, reference claim 22 teaches wherein the urolithin is urolithin A. Regarding instant claim 11, reference claim 2 teaches the NAD+ precursor is NR. Regarding instant claim 12, reference claim 23 teaches wherein the composition is a pharmaceutical or nutritional composition. Regarding instant claim 13, reference claim 2 teaches wherein the subject has lymphoma, multiple myeloma or leukemia, each of which is associated with anemia, leukopenia and/or thrombocytopenia as well as myelodysplastic syndrome for multiple myeloma. Regarding instant claim 20, reference claim 24 teaches wherein the combination composition is in the form of a food product, food supplement, nutraceutical, food for special medical purpose (FSMP), nutritional supplement, dairy-based drink, liquid supplement or meal replacement beverage. Regarding instant claim 21, the reference claims all the same method steps and, thus, all recited results necessarily and naturally flow from performing the method absent evidence to the contrary and claim 21 is rendered obvious for the same reasons set forth above for claim 8. To the extent any of these results are argued to be absent, then the active steps as recited in claim 21 or 8 lack sufficient detail to ensure the said results would predictably occur. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 8-9, 11-12, and 20-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3-10 and 13-17 of the “reference application” US 18/836,884.
Claim 16 of the reference application is directed to a method of treating cancer (or tumor formation) in a subject having already received a therapy, such as comprising radiation or chemotherapy (as in claim 10), the method comprising administering a therapeutically effective amount of a composition comprising a urolithin, a NAD+ precursor, and a Vitamin B12, wherein the NAD+ precursor is Nicotinic Acid, Nicotinamide, Nicotinamide Riboside (NR), Reduced Nicotinamide riboside (NRH), Nicotinamide Mononucleotide (NMN), Nicotinic acid mononucleotide, Nicotinic acid riboside, or a mixture thereof; including wherein the subject is immunocompromised (as in claim 3). Thus, the subject matter of instant claims 8 and 11 are rendered obvious.
Regarding instant claim 9, reference claim 6 teaches wherein the urolithin is urolithin A. Regarding instant claims 12 and 20, reference claim 13 teaches wherein the composition is a pharmaceutical composition or a food, food supplement, nutraceutical or nutritional supplement (nutritional composition). Regarding instant claim 21, the reference claims all the same method steps and, thus, all recited results necessarily and naturally flow from performing the method absent evidence to the contrary and claim 21 is rendered obvious for the same reasons set forth above for claim 8. To the extent any of these results are argued to be absent, then the active steps as recited in claim 21 or 8 lack sufficient detail to ensure the said results would predictably occur. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to arguments
The previous double patenting rejections in view of US 18/246,710 are withdrawn in view of amendments to the reference claims. Applicant’s remarks filed 5/22/26 (pg. 13) have been fully considered but are not considered responsive. The double-patenting rejections will not be held in abeyance. See 37 C.F.R. 1.111(b), which allows that some objections or “requirements as to form” may be held in abeyance but includes no provision for holding rejections in abeyance. Section 1.111(b) also requires applicants to respond to each rejection with “arguments pointing out the specific distinctions believed to render the claims, including any newly presented claims, patentable over any applied references.” For each rejection, for example, applicants might provide a proper terminal disclaimer (or at least indicate a willingness to submit one when double patenting is the only remaining issue); explain why the rejection is overcome by amendments; provide convincing arguments that the rejection was made in error; and/or explain why amendments or claim cancellations in the copending applications have rendered the rejection moot. If any of the conflicting pending application matures to a patent, modifying the rejection to account for claim-number changes will not constitute a new ground of rejection.
Conclusion
No claim is 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 ERIC J ROGERS whose telephone number is (571)272-8338. The examiner can normally be reached Monday - Friday 9:00-6:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Tracy Vivlemore can be reached on (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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/ERIC J ROGERS/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
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