Notice of Pre-AIA or AIA Status
The present application, filed on or after 16 Mar 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Claims 1-15 originally filed 13 Nov 2024 are pending and under consideration.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Objections
Claims 1-3, 5-6, 9, and 11-15 are objected to because of the following informalities:
Regarding claim 1, the phrase "senescence-associated secretory phenotype SASPs" should be corrected to "senescence-associated secretory phenotype (SASP)".
Regarding claim 2, the phrase "wherein the live tissue including at least one" should be corrected to "wherein the live tissue includes at least one".
Regarding claim 3, the phrase "including a least" recited in line 2 should be corrected to "including at least".
Regarding claims 5-6 and 9, the first instance of any abbreviation recited in the claims (such as BCL-2 in claim 5 line 4 and claim 9 line 5 and JAK1/2 in claim 6 line 2) should be accompanied by the full, written out term, then the abbreviation may be used alone thereafter.
Regarding claims 5 and 9, the symbol "+" should be corrected to use the word "and".
Regarding claims 5 and 9, the senolytic agent navitoclax, also termed ABT-263, is listed redundantly.
Regarding claims 11-15, the term senolytic is misspelled as "senoltyic".
Regarding claim 12, the phrase "comprising soaking the live tissue with the live tissue in aqueous media" should be corrected to "comprising soaking the live tissue in aqueous media".
Regarding claim 13, an unnecessary space is present in the word agent(s) in line 2.
Appropriate correction is required.
Claim Interpretation
To promote compact prosecution, the phrase "tyrosine kinase inhibitor (e.g., dasatinib) + quercetin" recited in claim 5 lines 2-3 and claim 9 lines 3-4 is interpreted as "the combination of a tyrosine kinase inhibitor and quercetin".
Claim Rejections - 35 USC § 112(b)
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.
Claims 1-15 are rejected under 35 U.S.C. § 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claims 1 and 8 are rejected under 35 U.S.C. § 112(b) on the basis that it is unclear how to reduce the amount of a qualitative variable. The claim limitations "wherein the amount of senescence-associated secretory phenotype SASPs is reduced" recited in claim 1 lines 7-8 and "reducing the amount of senescent cells and SASPs" in claim 8 lines 4-5 are unclear. Senescence-associated secretory phenotype (SASP) is a phenotype describing the overall state of a cell and is a qualitative assessment of cell phenotype, not quantitative. Therefore, a skilled artisan would be unable to recognize the metes and bounds of the claimed invention as it is unclear how SASP is reduced, rendering the claims indefinite. Claims 2-7 and 9-15 are included in the rejection as claims 2-7 depend from claim 1 and claims 9-15 depend from claim 8 and do not resolve the issue. To promote compact prosecution, the claims are interpreted to mean that at least one marker for SASP is reduced.
The term “enhanced” in claims 1 and 8 is a relative term which renders the claims indefinite. The term is not defined by the claims, 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. The specification does not provide any definition for which biological properties of the graft are enhanced and further does not provide for what degree the properties are enhanced. Claims 2-7 and 9-15 are included in the rejection as claims 2-7 depend from claim 1 and claims 9-15 depend from claim 8 and do not resolve the issue.
The term “normal” in claim 1 is a relative term which renders the claims indefinite. The term 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. The proportion of senescent cells in a tissue increases with age and with ischemia/reperfusion injury in organs from deceased donors. Therefore, because the proportion of senescent cells in normal tissue is not a static value, the standard of comparison to achieve a 15% reduction in the proportion of senescent cells and a 10% reduction in senescence-associated secretory phenotype is unclear. Claims 2-7 are included in the rejection as they depend from claim 1 and do not resolve the issue.
Claim 3 is rejected under 35 U.S.C. § 112(b) on the basis that the claim contains an improper listing of alternative limitations. Bone, which is included in the alternative as a soft tissue in lines 3-4, is not a soft tissue.
Claims 5, 6, and 9 are rejected under 35 U.S.C. § 112(b) on the basis that the use of parentheticals in the present case renders the claims indefinite. It is unclear whether the limitations within the parentheticals are part of the claimed invention or merely exemplary of the preceding limitation. See MPEP § 2173.05(d). Regarding claims 5 and 9, the parentheticals include species within each of the genera of flavonoids, tyrosine kinase inhibitors, alkanoids, and BCL-2 targeting agents. Regarding claim 6, a parenthetical includes the species ruxolitinib within the genera of JAK1/2 inhibitors.
The term “impacted” in claim 7 is a relative term which renders the claim indefinite. The term 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. It is unclear whether the claim limitation "tissue impacted with senescence" merely requires that senescent cells to be present in the tissue or requires for there to be an apparent pathological feature caused by the senescent cells.
The claim limitation "treating the tissue graft prior to storage ... during storage" recited in claim 14 lines 1-2 is self-contradictory, rendering the claim indefinite. It is unclear whether the claim requires treatment with senolytic agents or SASP inhibitors prior to storage or during storage. To promote compact prosecution, the claim is interpreted to mean that treatment occurs prior to storage.
Claim Rejections - 35 USC § 101
35 U.S.C. § 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-3 and 7 are rejected under 35 U.S.C. § 101 because the claimed invention is directed to a natural product without significantly more. The claims recite a viable tissue graft wherein the amount of senescent cells and senescence-associated secretory phenotype (SASP) is reduced compared to normal tissue or cells. This judicial exception is not integrated into a practical application because the claimed viable tissue graft is not markedly different than its naturally occurring counterpart – normal tissue in healthy, young animals compared to healthy, aged animals. The claims do not include additional elements sufficient to amount to significantly more than the judicial exception there are no additional elements that do not already describe naturally occurring tissue from young animals.
Iske (J. Iske, et al., Nat Commun, 2020) teaches comparisons in the amount of senescent cells and markers for SASP between young (2 mo.) and aged (18 mo.) mice (Abstract and throughout). Iske teaches that "[a]ging is associated with increased senescent cell burden" and that senescent cell have a pro-inflammatory secretome (the SASP), which includes the release of damage-associated molecular patterns (DAMPs), such as free mitochondrial DNA (mtDNA) (p. 2). Iske teaches that in skin, heart, and kidney about 1%, about 2%, and about 2%, respectively, of cells are senescent in young mouse tissue, whereas about 8%, about 10%, and about 10%, respectively, or cells are senescent in old mouse tissue (Results p. 6 and Fig. 4a and 4b). Therefore, young skin, heart, and kidney in mice have about 800%, about 500%, and about 500%, respectively, fewer senescent cells than healthy aged tissue. Moreover, levels of circulating mtDNA, which is released from multiple tissues with SASP, is about 0 pg/mL in young mice and about 2000 pg/mL in old mice, which is much greater than the 15% reduction in markers for SASP as required by claim 1 (Results p. 6 and Fig. 6b). Iske further teaches use of tissue from young mice as allografts for transplanting into other mice (viable tissue graft comprising live tissue) (Abstract and throughout).
The Office published the guidance document entitled 2014 Interim Guidance on Patent Subject Matter Eligibility (Interim Eligibility Guidance), published 16 Dec 2014. Step 2A was revised to include two prongs (Federal Register / Vol. 84, No. 4 / 07 Jan 2019).
Analysis is as follows:
Step 1: Is the claim drawn to one of the statutory categories of invention (a process, a machine, a manufacture, and/or a composition of matter)?
Step 1: The claim is directed to a composition of matter (viable tissue graft wherein the amount of senescent cells and SASP is reduced compared to normal tissue or cells).
Step 1: Yes.
Step 2A, Prong One: Does the claim recite a judicial exception (a law of nature, a natural product/phenomenon, or an abstract idea)?
Step 2A, Prong One: The composition of matter (viable tissue graft) is directed to a natural product. The claim recites a composition that is not markedly different from normal tissue in healthy, young animals compared to healthy, aged animals.
Step 2A, Prong One: Yes.
Step 2A, Prong Two: Does the claim recite additional elements that integrate the judicial exception into practical application of the exception?
Step 2A, Prong Two: This exception is not integrated into practical application because the claims do not recite additional elements that integrate the judicial exception into practical application. The claims merely recite elements found naturally in young animal tissue or describe where the tissue is sourced from. See MPEP § 2106.05(h).
Step 2A, Prong Two: No.
Step 2B: Does the claim recite additional elements that individually or in combination amount to significantly more than the judicial exception (i.e., whether the additional elements provide an inventive concept)?
Step 2B: The claims merely recite elements found naturally in young animal tissue or describe where the tissue is sourced from and, therefore, there are no additional elements that could amount to significantly more.
Step 2B: No.
The markedly different characteristics analysis performed in Step 2A, Prong One is a comparison of the nature-based product limitation to its naturally occurring counterpart in its natural state. Markedly different characteristics can be expressed as the product’s structure, function, and/or other properties. Product of nature exceptions include both naturally occurring products and non-naturally occurring products that lack markedly different characteristics from any naturally occurring counterpart. See MPEP § 2106.04(b)(II). If the claim recites a nature-based product limitation that does not exhibit markedly different characteristics, the claim is directed to a product of nature exception, and the claim will require further analysis to determine eligibility based on whether additional elements add significantly more to the exception. In accordance with this analysis, viable tissue graft, for example, is eligible when there is a resultant change in characteristics sufficient to show a marked difference from young animal tissue. It is concluded here that the claimed viable tissue graft is not markedly different from its naturally occurring counterpart, young animal tissue, as the claim does not recite structural limitations that distinguish the viable tissue graft composition from the composition of young animal tissue.
The Supreme Court has identified several considerations for determining whether a claim with additional elements amounts to significantly more than the judicial exception itself. Limitations that may qualify as significantly more when recited in a claim with a judicial exception include: improvements to another technology or technical field; improvements to the functioning of the computer itself; applying the judicial exception with, or by use of, a particular machine; effecting a transformation or reduction of a particular article to a different state or thing; adding a specific limitation other than what is well-understood, routine and conventional in the field, or adding unconventional steps that confine the claim to a particular useful application; or other meaningful limitations beyond generally linking the use of the judicial exception to a particular technological environment.
Limitations that were found not to be enough to qualify as significantly more when recited in a claim with a judicial exception include: adding the words ‘apply it’ (or an equivalent) with the judicial exception; mere instructions to implement an abstract idea on a computer; simply appending well-understood, routine and conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception; adding insignificant extra-solution activity to the judicial exception; or generally linking the use of the judicial exception to a particular technological environment or field of use.
In the instant case, the limitations of the claims do not impose limits on the scope of the claim such that the viable tissue graft wherein the amount of senescent cells and SASP is reduced compared to normal tissue or cells is markedly different from a naturally occurring product. Accordingly, based on analysis of the claim as a whole, the claims do not recite additional elements adding significantly more than the judicial exception and are thus rejected under 35 U.S.C. § 101 because the claimed invention is not directed to patent eligible subject matter.
Claim Rejections - 35 USC § 112(a)
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.
Claims 5 and 9 are rejected under 35 U.S.C. § 112(a) as failing to comply with the written description requirement. The claims contain 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 at the time the application was filed had possession of the claimed invention.
Claims 5 and 9 are drawn to several classes of senolytic agents. However, the claims encompass species of flavonoids, tyrosine kinase inhibitors (TKI), alkanoids, curcumin analogues, and B cell lymphoma 2 (BCL-2)-targeting agents that a skilled artisan would not recognize as senolytic agents. The specification provides exemplary species for each of the classes except for curcumin analogues: quercetin and fisetin as flavonoids, dasatinib as a TKI, piperlongumine as an alkanoid, and navitoclax (also referred to in the art as ABT-263) and ABT-737 as BCL-2 targeting agents (par. 49, 59, and 63). The specification does not provide any contemplation of specific compounds regarded as analogues of curcumin. The specification has not described a structure-function relationship between the exemplary species and the required function as a senolytic agents such that a skilled artisan could envision the detailed structure of at least a representative number of species for each of the broad genera of flavonoids, TKI, alkanoids, curcumin analogues, and BCL-2 targeting agents as senolytic agents.
The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) (“[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.”). The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, such as physical and/or chemical properties, functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show that the inventor was in possession of the claimed genus. See MPEP § 2163(II)(A).
Regarding flavonoids, Yousefzadeh (M.J. Yousefzadeh, et al., EBioMedicine, 2018) teaches that comparison of senolytic activity between several flavonoid compounds, including quercetin and fisetin (Abstract and Introduction p. 19). Yousefzadeh demonstrates that out 11 tested structurally diverse flavonoids, only fisetin and curcumin could reduce the number of Ercc1-null mouse embryonic fibroblasts (MEF) (Results p. 21 and Fig. 1). Yousefzadeh further teaches that while fisetin has numerous biological effects relevant to reduction in senescent cell burden, it is unclear whether many of the observed biological effects are actually due to its senolytic activity (Discussion p. 26). Furthermore, Yousefzadeh teaches that fisetin and quercetin, another flavonoid commonly used as a senolytic agent, are highly structurally similar with only a single substitution, which putatively explains why they exert many similar effects (Discussion p. 26). Thus, the art only contemplates a narrow structure-function relationship between two highly related compounds with senolytic activity that is insufficient to generalize to other flavonoids. Therefore, there is insufficient structure-function relationship between flavonoids and senolytic activity for a skilled artisan to recognize that the joint inventors have possession of the entire genus of flavonoids as senolytic agents.
Regarding the combination of tyrosine kinase inhibitors and quercetin, Childs (B.G. Childs, et al., Nat Rev Drug Discov, 2017) teaches that quercetin has a "myriad of presumed biological effects" and that dasatinib is an inhibitor of numerous receptor tyrosine kinases and because both drugs have such broad spectra of biological effects, it is difficult to ascertain which observed biological effects are specific to senolysis (p. 727 and Table 2). Furthermore, Mukherjee (A. Mukherjee, et al., Cell Death Discov, 2023) teaches that TL02-59, an inhibitor of fibroblast growth factor receptor (FGFR, a receptor tyrosine kinase), reduces the release of profibrotic chemokines (a feature of senescence-associated secretory phenotype (SASP)) without reducing the number of senescent cells (Abstract). Therefore, there is insufficient structure-function relationship between tyrosine kinase inhibitors and senolytic activity for a skilled artisan to recognize that the joint inventors have possession of the entire genus of the combination of tyrosine kinase inhibitors and quercetin as senolytic agents.
Regarding alkanoids, Wang (Y. Wang, et al., Aging, 2016) teaches comparison of senolytic activity between the alkaloid piperlongumine (PL) and its analogues 2,3-dihydro-PL and 7,8-dihydro-PL (Results p. 2916 and Fig. 1). PL is strongly senolytic and 7,8-dihydro-PL is weakly senolytic against WI-38 fibroblasts infrared irradiated to induce senescence, whereas 2,3-dihydro-PL was ineffective (Results p. 2916 and Fig. 1). Furthermore, Wang demonstrates that the senolytic activity of PL and its analogue PL-FPh is dependent on induction of reactive oxygen species (ROS) in target cells, whereas the PL analogues BRD4809, a PL dimer, and PL-7 are senolytic but do not induce ROS or inhibit ROS production (Results p. 2918 and Fig. 3). Therefore, there is insufficient structure-function relationship between alkanoids and senolytic activity for a skilled artisan to recognize that the joint inventors have possession of the entire genus of alkanoids as senolytic agents.
Regarding curcumin analogues, Li (W. Li, et al., Aging, 2019) teaches comparison of senolytic activity between curcumin analogues EF24, HO-3867, 2-HBA, and dimethoxycurcumin (DMIC) (Results p. 772, Fig. 1, and Table 1). EF24, HO-3867, 2-HBA are senolytic against WI-38 fibroblasts infrared irradiated to induce senescence, whereas DMIC is not senolytic (Results p. 772, Fig. 1, and Table 1). Li further teaches that the mechanism by which the most potent of the listed analogues, EF24, induces death in senescent cells is unknown (Discussion p. 777). Furthermore, Hendrayani (S.F. Hendrayani, et al., Neoplasia, 2013) teaches that curcumin can induce senescence in cancer-associated fibroblasts and myofibroblasts (Abstract). Therefore, there is insufficient structure-function relationship between curcumin analogues and senolytic activity for a skilled artisan to recognize that the joint inventors have possession of the entire genus of curcumin analogues as senolytic agents.
Regarding BCL-2-targeting agents, Zhu (Y. Zhu, et al., Aging Cell, 2016) teaches comparison of senolytic activity between the BCL-2 targeting small molecules navitoclax and TW-37 (CAS Registry No. 877877-35-5) (Abstract). Zhu demonstrates that navitoclax induces apoptosis in senescent human umbilical vein endothelial cells (HUVECs) and IMR90 (a human lung fibroblast cell line) (senolytic), whereas TW-37 has little senolytic activity in either of the three senescent cell types (Abstract, Results p. 429, and Fig. 2 and 3). Zhu further teaches that merely targeting BCL-2 is not sufficient to broadly induce apoptosis in senescent cells by demonstrating through small interfering RNA (siRNA) knockdown of BCL family members that knockdown of BCL-2, BCL-xl, and BCL-w, the targets of navitoclax, is required for senolytic activity in multiple cell types, whereas siRNA knockdown of BCL-2, BCL-xl, and MCL-1, the targets of TW-37, is not senolytic (Results p. 431 and Fig. 4). Therefore, there is insufficient structure-function relationship between BCL-2 targeting and senolytic activity for a skilled artisan to recognize that the joint inventors have possession of the entire genus of BCL-2 targeting agents as senolytic agents.
Claim Rejections - 35 USC § 102
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 1-14 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by Kirkland (US 2021/0283185 A1, 2021).
Regarding claims 1 and 8, Kirkland discloses transplantation of hearts (a cardiac allograft) from old (18 mo.) donor mice into young (2 mo.) recipient mice (viable tissue graft) and a method of preparing the graft (Example 4 par. 145-150). Kirkland discloses treating the donor prior to harvesting the graft to reduce the proportion of senescent cells in the heart from about 10% to about 2%, a 500% reduction (reduced amount of senescent cells, claims 1 and 8, and at least 15%, claim 1 line 5) (Example 4 par. 145-150 and Fig. 30A middle row). Additionally, treatment reduced the amount mitochondrial DNA (mtDNA) in circulation from about 2000 pg/mL to about 500 pg/mL, a 400% reduction, the amount of CD4+ IL17A+ cytotoxic T cells in circulation from about 11% to about 7%, a 57% reduction, the amount of CD4+ IFNγ+ cytotoxic T cells in circulation from about 13% to about 11%, an 18% reduction, the amount of CD8+ IL17A+ cytotoxic T cells in circulation from about 2.5% to about 2%, a 25% reduction, and the amount of CD8+ IFNγ+ cytotoxic T cells in circulation from about 35% to about 25%, a 40% reduction (reduced amount of senescence-associated secretory phenotype (SASP) markers, claims 1 and 8, and at least 10% reduction, claim 1 lines 7-9) (Example 4 par. 145-150 and Fig. 30B left panel and 30C). The measurements for the amount of senescent cells and SASP markers are in comparison to healthy, aged, untreated mice (reduced amount compared to normal tissue/cells, claim 1) (Example 4 par. 150).
Regarding claim 2, the tissue graft disclosed by Kirkland is an allograft (allogenic tissue) (Example 4 par. 145-150).
Regarding claim 3, the tissue graft disclosed by Kirkland is heart, which comprises pericardium, nerves (nervous tissue), blood vessels, heart valves, muscle, and is a whole organ (Example 4 par. 145-150).
Regarding claims 4, 6, and 10, Kirkland discloses in an alternative embodiment further treating tissues or organs for transplant (viable tissue graft) with a senotherapeutic agent (senolytic agent or SASP inhibitor) after harvesting but before transplantation in an organ preservation solution (during storage) to maintain the regenerative capacity of the tissue to be transplanted (par. 172 and 174). Such senotherapeutic agents include senomorphic agents to suppress senescent phenotype (SASP inhibitor, claims 6 and 10) (par. 50). Kirkland discloses that the senomorphic agent may be ruxolitinib, metformin, or rapamycin (claims 6 and 10) (par. 50).
Regarding claims 5 and 9, Kirkland discloses treating the donor mice with quercetin and (a flavonoid) and dasatinib (a non-specific tyrosine kinase inhibitor) to reduce the amount of senescent cells and the amount of markers for SASP in the cardiac allograft (Example 4 par. 145). Kirkland further discloses in different embodiments that senolytic agents to reduce the amount of senescent cells in a tissue can include navitoclax (a BCL-2-targeting agent, CAS Registry No. 923564-51-6, also referred to as ABT-263), luteolin (a flavonoid), alvespimycin (CAS Registry No. 467214-20-6, also referred to as 17-DMAG), and piperlongumine (an alkanoid) (par. 50).
Regarding claim 7, the cardiac allograft disclosed by Kirkland comprises 10% senescent cells prior to treatment to reduce the amount of senescent cells in the tissue (from a tissue impacted with senescence) (Example 4 par. 145-150 and Fig. 30A middle row).
Regarding claim 10, Kirkland discloses in alternative embodiments treatment of a tissue graft with senomorphic agent to suppress senescent phenotype (SASP inhibitor) (par. 50). Kirkland discloses that the senomorphic agent may be ruxolitinib, metformin, or rapamycin (par. 50).
Regarding claim 11, Kirkland discloses in an embodiment perfusing an organ for transplant (tissue graft comprising live tissue) ex vivo with a solution comprising senolytics (washing the live tissue in aqueous media containing senolytic agents with a bioreactor system) (par. 119).
Regarding claims 12-13, Kirkland discloses in an embodiment storing a procured organ (tissue graft comprising live tissue) in a preservation solution comprising a senolytic agent (soaking the live tissue in aqueous media containing senolytic agents, claim 12, storing the tissue graft in an aqueous media with senolytic agents to mitigate accumulation of senescent cells during storage, claim 13) (par. 119).
Regarding claim 14, Kirkland discloses treating the cardiac allograft to reduce the amount of senescent cells while the heart is still within the donor, and the hearts experienced an average ischemia time (time between harvesting and transplant, storage) of 40 min (treating the tissue prior to storage) (Example 2 par. 106 and Example 4 par. 145-150).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. § 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-15 are rejected under 35 U.S.C. § 103 as being unpatentable over Kirkland (US 2021/0283185 A1, 2021) in view of Matsunaga (T. Matsunaga, et al., Curr Opin Organ Transplant, 2022).
Kirkland teaches tissue grafts and a method of reducing the amount senescent cells and markers for senescence-associated secretory phenotype (SASP) in the grafts as discussed in the rejection of claims 1-14 under 35 U.S.C. § 102 above.
Kirkland does not teach treatment of the tissue graft with aqueous media comprising senolytic agent and/or SASP inhibitor after storage and prior to transplantation as required by claim 15.
However, Kirkland further teaches that treating the graft to be transplanted, rather than the donor or recipient themselves, "can limit side effects to the transplant recipients" (par. 172). Kirkland further teaches that the tissue graft may be stem cells, pancreatic islets, cornea, skin, blood vessels, heart valves, bone, heart, lung, kidney, liver, pancreas, intestine, and scalp or hair (par. 54).
Furthermore, Matsunaga teaches that "preliminary data have shown that senolytics can deplete senescent cells from discarded human kidneys perfused by cold MP" (machine perfusion) (p. 6). Matsunaga further teaches that "perfusing old organs with senolytics may help to expand the donor pool and improve outcomes of transplants specifically from older donors". (p. 6). Therefore, Matsunaga teaches treatment of the tissue graft after cold storage and before transplantation.
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to combine the method of reducing the amount of senescent cells and markers for SASP in tissue grafts as taught by Kirkland with the method of treating the tissue graft with a senolytic agent after storage and prior to transplantation as taught by Matsunaga to arrive at the claimed invention. One would be motivated to make such a combination as Kirkland teaches that treatment of the graft itself rather than the donor or recipient can reduce side effects of the senolytic agent and as Matsunaga teaches that depleting senescent cells in old organs can expand the pool of organs for transplant. One would have a reasonable expectation of success in making the combination as Matsunaga teaches that treatment of kidney with a senolytic agent during ex vivo organ perfusion could deplete senolytic cells.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Eric B Wright whose telephone number is (571) 272-2607. The examiner can normally be reached Mo - Fr, 09:00 a.m. - 05:00 p.m. Eastern. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached at (571) 272-4517.
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Eric B Wright, PhD
Examiner
Art Unit 1632
/Eric B Wright/Examiner, Art Unit 1632
/VALARIE E BERTOGLIO/Primary Examiner, Art Unit 1632
Prosecution Insights