DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This is the third Office action on the merits of the claims.
All citations to the Manual of Patent Examining Procedure (MPEP) refer to Revision 01.2024, which was released in November 2024.
Continued Examination
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant’s submission filed on 01 October 2025 has been entered.
Status of the Claims
Applicant amended claims 3, 38, and 98-99, and cancelled claims 74-77, 79, 81, 84, 86-87, 89-90, 92, 95, 97, and 100-101. Claims 1-2, 4-28, 30-31, 33-37, 39-72, 78, 80, 82-83, 85, 88, 91, 93-94, and 96 were cancelled previously by Applicant. Claims 3, 29, 32, 38, 73, and 98-99 are pending.
Status of the Rejections
The utility rejections of the claims under 35 U.S.C. 101 and 35 U.S.C. 112(a) are new.
The rejection of the claims under 35 U.S.C. 112(b) has been modified in view of Applicant’s recent claim amendments.
The rejection of claims 3, 6-7, 29, 32, 38, 73-77, 79, 81, 84, 86-87, 89-90, 92, and 95 under 35 U.S.C. 102(a)(1) as being anticipated by Geiger (US 2015/0297563 A1) has been withdrawn in view of Applicant’s narrowing claim amendments.
The rejection of claim 95 under 35 U.S.C. 103 as being unpatentable over Geiger (US 2015/0297563 A1) in view of Han (“Epigenetic age-predictor for mice based on three CpG sites.” Elife 7 (2018): e37462) has been withdrawn in view of Applicant’s cancellation of that claim.
The rejection of claims 3, 29, 32, 38, 73, and 98-99 under 35 U.S.C. 103 as being unpatentable over Geiger (US 2015/0297563 A1) in view of Buckinx (“Burden of frailty in the elderly population: perspectives for a public health challenge.” Archives of public health 73.1 (2015): 19) is new.
All three rejections on the ground of non-statutory double patenting set forth in the previous Office action (06 August 2025) are withdrawn in view of Applicant’s narrowing amendments to claim 3. The examiner appreciates Applicant’s effort to advance prosecution.
Utility Rejections under 35 U.S.C. 101 and 35 U.S.C. 112(a)
Claims 3, 29, 32, 38, 73, and 98-99 are rejected under 35 U.S.C. 101 because the claimed invention — to the extent it is merely directed to reducing elevated levels of circulating interferon γ, circulating interleukin 1-α, or circulating interleukin 1-β (each without regard to treating a disease or other medical condition) — is not supported by either a specific and substantial asserted utility asserted utility or a well-established utility.
In Step (a) of claim 3, when a member of the Markush group recited therein other than age-related depression, age-related sarcopenia, or age-related frailty is selected, the claim is essentially directed to the treatment of an unspecified disease or condition. It follows that claim 3 does not satisfy the “substantial utility” requirement of 35 U.S.C. 101. MPEP § 2107.01(I)(B). Furthermore, reducing elevated levels of circulating interferon γ, circulating interleukin 1-α, or circulating interleukin 1-β by 50% in the general population (see Steps (a) and (b) of claim 3), does not provide a well-defined and particular benefit to the public. Consequently, claim 3 also fails to satisfy the “specific utility” requirement of 35 U.S.C. 101. MPEP § 2107.01(I)(A) (“A ‘specific utility’ is specific to the subject matter claimed and can ‘provide a well-defined and particular benefit to the public.’”), quoting In re Fisher, 421 F.3d 1365, 1371 (Fed. Cir. 2005).
Claims 3, 29, 32, 38, 73, and 98-99 are also rejected under 35 U.S.C. 112(a). Specifically, because the claimed invention is not supported by either a specific and substantial asserted utility or a well-established utility for the reasons set forth above, one skilled in the art clearly would not know how to use the claimed invention. MPEP § 2107.01(IV).
Claim Rejections - 35 U.S.C. 112(b)
The following is a quotation of 35 U.S.C. 112(b):
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 3, 29, 32, 38, 73, and 98-99 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter that the inventors regard as the invention.
Regarding claim 3, the following three limitations are unclear: “an elevated level of circulating interferon γ”; “an elevated level of circulating interleukin 1-α”; “an elevated level of circulating interleukin 1-β.” Where is the boundary between elevated levels and non-elevated levels of circulating interferon γ? The specification provides insufficient guidance concerning this matter. Similarly, the specification provides insufficient guidance concerning both (i) the boundary between elevated levels and non-elevated levels of circulating interleukin 1-α and (ii) the boundary between elevated levels and non-elevated levels of circulating interleukin 1-β. The examiner notes that Figures 1(e), 1(f) and 1(g), which show a marked increase in those levels in aged mice, is insufficient to clarify claim 3, especially considering the limitations concerning the elevated levels generically encompass all organisms regardless of age. For example, what qualifies as an elevated level of circulating interferon γ in a 30-year-old human? The only other relevant disclosure is set forth in paragraphs [0303] and [0305] on pages 87-88 of the specification, as originally filed (WO 2021/034616). However, that disclosure is too superficial to clarify claim 3. See para. [0303] (“Data showed a marked increase in the concentrations of INFγ, IL-1β and IL-1α on aging and the concentrations of these cytokines were similar to concentrations in young animals upon CASIN treatment of aged animals (Figures 1e-g).”) and para. [0305] (“Without being bound by any theory, elevated concentrations of interferon γ, as detected in these experiments may be a conserved hallmark of aging and might be functionally linked to lifespan. Similarly, both Interleukin 1α and Interleukin 1β have been associated with many aging-associated phenotypes and diseases.”). In sum, persons having ordinary skill in the art can reasonably disagree over which levels of circulating interferon γ, interleukin 1-α, and/or circulating interleukin 1-β qualify as elevated and, conversely, which do not. MPEP § 2173.05(b)(I) (terms of degree); see also MPEP § 2173.04 (“a genus claim that could be interpreted in such a way that it is not clear which species are covered would be indefinite (e.g., because there is more than one reasonable interpretation of what species are included in the claim)”). Therefore, claim 3 and all claims depending thereon are indefinite.
In further regard to claim 3, it is unclear whether the mental step of identifying a subject as having age-related depression, age-related, etc., via clinical diagnosis actually limits the patient population. Claim 3 must be clarified by defining the subject, itself, as having the relevant disease or condition. This is traditionally accomplished in the preamble of the claim, as shown in the following example: “A method of treating age-related depression or age-related sarcopenia in an elderly human in need thereof….” In the interest of compact prosecution, the examiner notes that focusing claim 3 in the manner reflected in the foregoing preamble is likely to significantly advance prosecution of this application. Other subject matter (e.g., age-related frailty) can be pursued in a continuation application, if desired.
In further regard to claim 3, can a human other than an elderly human actually have age-related depression, age-related sarcopenia, or age-related frailty? See MPEP § 2173.04 (quoted above). The examiner recommends that Applicant clarify claim 3 by incorporating claim 29.
Claim Rejections - 35 U.S.C. 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 3, 29, 32, 38, 73, and 98-99 are rejected under 35 U.S.C. 103 as being unpatentable over Geiger (US 2015/0297563 A1) in view of Buckinx (“Burden of frailty in the elderly population: perspectives for a public health challenge.” Archives of public health 73.1 (2015): 19).
Geiger is directed to “methods and pharmaceutical compositions for rejuvenating hematopoietic stem cells and progenitor cells from blood, intestinal tissue and dermal tissue by administration of at least one inhibitor of a GTPase, such as Cdc42 GTPase.” Abstract.
Geiger discloses: “Embodiments disclosed herein relate to methods for rejuvenating a precursor cell in a subject. In specific embodiments, methods and pharmaceutical compositions are provided for rejuvenating a blood precursor cell, a dermal epithelial precursor cell or an intestinal epithelial precursor cell in a subject, comprising administering to a subject in need of treatment an effective amount of at least one Cdc42-specific inhibitor.” (Emphasis added) Para. [0007].
Geiger identifies CASIN, as well as all four of the other chemical compounds now recited in claim 3 of the present application, as exemplary Cdc42-specific inhibitor compounds. Paras. [0008], [0161].
Geiger discloses: “Recent developments on molecular and cellular mechanisms of aging have confirmed that the functional decline in hematopoiesis in the elderly, which involves a progressive reduction in the immune response and an increased incidence of myeloid malignancy, is linked to aging of hematopoietic stem cells (HSCs). However, until recently, there was broad consensus that the phenotype of aged HSCs is fixed and dominated by cell-intrinsic regulatory mechanisms that could not be reverted by therapeutic intervention.” (Emphasis added) Para. [0058].
Geiger discloses: “Presented herein is the surprising discovery that the elevated activity of the small RhoGTPase Cdc42 in aged precursor cells including HSCs plays a role in causing HSC aging and correlates with apolarity of aged HSCs, and that pharmacological inhibition of Cdc42 activity functionally rejuvenates aged HSCs and increases the percentage of polarized cells among aged HSCs to the level found in young. This discovery consequently implies a novel and critical mechanistic role for Cdc42 activity in HSC aging, identifying Cdc42 activity as a pharmacological target for ameliorating cell intrinsic stem cell aging.” (Emphasis added) Para. [0059].
Geiger discloses: “In some embodiments herein, the methods include administering a Cdc-specific inhibitor to a subject in need of treatment. In some embodiments, a subject in need of treatment can comprise a subject having a population of blood precursor cells, dermal epithelial precursor cells or intestinal epithelial precursor cells that exhibit a phenotype typical of an aging cell. In some embodiments, a subject in need of treatment is an elderly subject, as is understood in the art. For example, the age of the subject can be at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% of the life expectancy for that species, or of the life expectancy for that species and gender. For example, the subject in need of treatment can be a human subject older than about 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79 or older than about 80 years old.” (Emphasis added) Para. [0071].
Although Geiger discloses administering an effective amount of at least one Cdc42-specific inhibitor to an elderly person who (i) is older than about 80 years old and/or (ii) has an age that is at least 100% of the life expectancy for that species, Geiger is silent to whether that elderly person can be frail. Consequently, Geiger does not anticipate the following member of the Markush group recited in Step (a) of claim 3: “age-related frailty.” As explained below, Buckinx compensates for this deficiency.
Buckinx is directed to the burden of frailty in the elderly population.
Buckinx teaches: “Frailty is very common in older people. According to various studies, the prevalence of frailty in community dwelling elderly adults varies from 4.0% to 59.1%, seems to increase with age, appears to be greater in women than in men and is more prevalent in people, with lower education and income, with poorer health and higher rates of comorbid chronic disease and disability.” (Emphasis added) Page 3 of 7.
Buckinx teaches: “Indeed, Collard’s meta-analysis shows that the average prevalence of frailty was statistically significantly higher in women (9.6%, 95% CI: 9.2-10%) than in men (5.2%, 95% CI: 4.9-5.5%) (p < .001). Another study in 2010 shows convergent results since the prevalence of frailty was higher in women (60.1%) than in men (40.4%), (p < .001). This article also highlights that the prevalence increases with each 5-year age group before reaching a ‘stable value’ (15.3% among 65–69 years; 18.6% among 70–74 years; 23.5% among 75–79 years; 22.4% among 80–84 years; 20.2% over 85 years). Fried also notes that prevalence of frailty increases with each 5-year age group (3.2% among 65–70 years; 5.3% among 71–74 years; 9.5% among 75–79 years; 16.3% among 80–85 years; 25.7% among 86–90 years; 23% over 90 years).” (Emphasis added) Pages 3-4 of 7.
Buckinx teaches: “Reducing the severity of frailty is supposed to provide large benefits for individuals, their families and for the society. Treating frailty in older people seems a realistic therapeutic and preventive goal.” Page 5 of 7.
Before the effective filing date of the claimed invention, the foregoing teachings of Buckinx would have motivated a person having ordinary skill in the art to modify Geiger by administering an effective amount of the Cdc42-specific inhibitor to an elderly person who is also frail, in an effort to treat his/her frailty by rejuvenating aged hematopoietic stem cells (HSCs). MPEP § 2141.03(I) (“‘A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton’”) and (“‘Office personnel may also take into account ‘the inferences and creative steps that a person of ordinary skill in the art would employ’”).
Claim 3 additionally requires that the amount of the administered the Cdc42-specific inhibitor is “effective to decrease the level of circulating interferon γ, the level of circulating interleukin 1-α, or the level of circulating interleukin 1-β by 50%.”
Geiger discloses: “Orally, the compounds according to the preferred embodiments are suitable administered at the rate of 100 μg to 100 mg per day per kg of body weight. Preferably, orally, the compounds according to the preferred embodiments are suitable administered at the rate of about 100, 150, 200, 250, 300, 350, 400, 450, or 500 μg to about 1, 5, 10, 25, 50, 75, 100 mg per day per kg of body weight.” Para. [0297]; see also para [0298] (similar ranges for parenteral administration).
There is considerable overlap between the effective amounts disclosed in Geiger and the amounts identified as “therapeutically effective” by Applicant in paragraph [0238] on page 57 of the specification of the present application, as originally filed (WO 2021/034616). This provides a sounds basis for the examiner’s position that the range of effective amounts disclosed in Geiger substantially includes amounts that satisfy Applicant’s functional limitation — i.e., amounts of Cdc42-specific inhibitor capable of decreasing the level of circulating interferon γ, the level of circulating interleukin 1-α, or the level of circulating interleukin 1-β by 50%. MPEP § 2144.05(I) (“In the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists.”); see also MPEP § 2112.02(II) (“‘While the references do not show a specific recognition of that result, its discovery by appellants is tantamount only to finding a property in the old composition.’”), quoting In re Tomlinson, 363 F.2d 928, 934 (CCPA 1966).
Therefore, claims 3, 29, and 73 are prima facie obvious.
Regarding claim 32, Applicant is referred to paragraph [0342] of Geiger, which discloses twice daily administration of effective amounts of CASIN (a Cdc42-specific inhibitor). See also paras. [0381], [0384], and [0396].
Regarding claim 38, Applicant is referred to paragraphs [0011], [0059], [0075], [0078], and [0379], which concern elevated Cdc42 activity. Geiger additionally discloses that “GTP-bound Cdc42 levels relative to total Cdc42 are measured by pulldown/Western Blot assay and compared as a ratio to the levels observed in non-aged or young cells.” Para. [0079]; see also para. [0370]. Before the effective filing date of the claimed invention, it would have been obvious to a person having ordinary skill in the art to determine the level of Cdc42 activity in the elderly patient prior to commencement of treatment, in order to establish a baseline for evaluating the effectiveness of the Cdc42-specific inhibitor therapy. MPEP § 2141.03(I) (“‘A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton’”) and (“‘Office personnel may also take into account ‘the inferences and creative steps that a person of ordinary skill in the art would employ’”).
Regarding claim 73, Applicant is referred to paragraph [0008] of Geiger, which identifies CASIN as a preferred Cdc42-specific inhibitor and shows its chemical structure. See also claim 35 of Geiger (“wherein the Cdc42-specific inhibitor is CASIN”).
Regarding claims 98 and 99, Geiger discloses: “Orally, the compounds according to the preferred embodiments are suitable administered at the rate of 100 μg to 100 mg per day per kg of body weight. Preferably, orally, the compounds according to the preferred embodiments are suitable administered at the rate of about 100, 150, 200, 250, 300, 350, 400, 450, or 500 μg to about 1, 5, 10, 25, 50, 75, 100 mg per day per kg of body weight.” Para. [0297]; see also para [0298] (similar ranges for parenteral administration). Given the breadth of the serum concentration recited in each of claims 98 and 99 (“about 0.1 to about 10 μM”), the dosing ranges disclosed in Geiger are considered overlapping. MPEP § 2144.05(I) (“In the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists.”); see also MPEP § 2112.02(II) (“‘While the references do not show a specific recognition of that result, its discovery by appellants is tantamount only to finding a property in the old composition.’”), quoting In re Tomlinson, 363 F.2d 928, 934 (CCPA 1966).
Conclusion
Claims 3, 29, 32, 38, 73, and 98-99 are rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER ANTHOPOLOS whose telephone number is 571-270-5989. The examiner can normally be reached on Monday – Friday (9:00 am – 5:00 pm). If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bethany P. Barham, can be reached on Monday – Friday (9:00 am – 5:00 pm) at 571-272-6175. The fax number for the organization where this application or proceeding is assigned is 571-273-8300.
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/P.A./
10 November 2025
/BETHANY P BARHAM/Supervisory Patent Examiner, Art Unit 1611