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 .
DETAILED ACTION
Summary
This is a Non-Final Office action based on the 18/039641 application response filed on 07/23/2026.
Claims 3, 8, 10-11, 15, 17-23 & 56-57 are pending and have been fully considered.
Claims 1-2, 4-7, 9, 12-14, 16, 24-27 & 28-55 are cancelled.
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 07/23/2026 has been entered.
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 non-obviousness.
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 3, 8, 10-11, 15, 17-23 & 56-57 are rejected under 35 U.S.C. 103 as being obvious over BLENNOW in US 20190277864 in view of HAY in US 20170304391 in view of HAY2 in A Novel Angiotensin-(1-7) Glycosylated Mas Receptor Agonist for Treating Vascular Cognitive Impairment and Inflammation Related Memory Dysfunction.
With respect to Claim 3, BLENNOW teaches a method for detecting and treating a subject diagnosed as having cognitive impairment (abstract, paragraph 0036, 0108, 0137, 0139, 0158), which can be Alzheimer’s (paragraph 0009) and which can also be vascular caused dementia (paragraph 0023, 0026) comprising:
(a) determining/measuring from a blood fraction a neurofilament light protein (NFL) concentration and/or p-tau181 concentration in the subject (paragraph 0084, and see claim 1) and that the sample is serum (paragraph 0009, 0015),
(b) comparing the NFL level measured in step (a) and/or the p-tau181 level measured in step (a) to a pre-determined control or reference level (paragraph 0062-0063, 0101, 0130), and
Determining if in the measured level is increased in comparison to the control or reference, and if the level is increased, determining that the individual is at risk of or developing a neurodegenerative disease (paragraph 0101, 0130).
BLENNOW teaches that pre-symptomatic carriers have a measured level for a control of 16.7 pg.ml of NFL in serum (paragraph 0184). For symptomatic carriers, it teaches that the control level for serum Nfl is 46 pg/ml, so this reads on the claimed identifying the subject as having an NFL level greater than the predetermined control (Figure 4).
BLENNOW further teaches of monitoring the patient using these tactics over large periods of time, as in over 20 years, so making multiple measurements—so this reads on the claimed determining a second NFL concentration from the subject (paragraph 0109), and of monitoring a patient using these tactics including monitoring of a prophylactic treatment, so monitoring, detecting for the second time after a treatment (paragraph 0108, 0036). BLENNOW further teaches that in case an increase in value of NfL is determined over time, the risk of developing the neurodegenerative disease further increases, whereas a constant or decreased value at a later time point indicates that the risk of developing the neurodegenerative disease does not further increase, or decreases (paragraph 0109).
BLENNOW even further teaches that the prophylactic treatment can be a therapeutically effective amount of an anti-A betamer oligomer antibody such as aducanumab, or a cognitive enhancer such as mematine (paragraph 0139).
BLENNOW further teaches that in case an increase in value of NfL is determined over time, the risk of developing the neurodegenerative disease further increases, indicating that the prophylactic treatment is not successful, whereas a constant or decreased value indicates that the risk of developing the neurodegenerative disease does not further increase or decreases, indicating that the prophylactic treatment is successful (paragraph 0139).
BLENNOW further teaches of using NFL specifically as a marker of “treatment response” (paragraph 0195).
BELENNOW further teaches that treatment/therapy is only administered in cases where the individual is identified as being at risk of the cognitive disease or developing the disease (paragraph 0158), so this also reads on not administering treatment if the NFL level detected in one or multiple of the successive measurements is lower than the reference/control level(paragraph 0158, 0195, 0109).
This makes the instantly claimed limitation of “the therapeutically effective amount, administration frequency, or both, are maintained or reduced when a second NFL level is less than a first concentration,” as it makes obvious to perform no administration of treatment after administering a treatment if a second level of NFL is under the control level indicated. No treatment or stoppage or discontinuing of treatment can be considered “reduced,” treatment through broadest reasonable treatment.
BLENNOW does not teach of administering a therapeutic agent which is the claimed Mas receptor agonist to the patient.
HAY is used to remedy this and more specifically teaches of methods of using oligopeptides for treatment of diseases where cognitive dysfunction is present (abstract)--- which relates to the method taught by BLENNOW above of diseases where cognitive function is present and indicated by detection of NFL--- and HAY further teaches wherein the disease is Alzheimer’s (paragraph 0016, 0083, 0089) and even further where there are vascular/cerebrovascular associations to the cognitive dysfunction (paragraph 0083, 0087-0089).
Even further HAY teaches that an oligopeptide treatment is used which is (Ang-1-7) (paragraph 0003) and this oligopeptide is a Mas receptor agonist (paragraph 0091). HAY teaches that a therapeutically effective amount of the treatment is administered (paragraph 0014, 0051, 0082) and that it is known to have effects on both endothelial cells a neurons of the neurovascular units which contain neurons, microglia, and endothelial cells (paragraph 0087).
With respect to the claimed reduction in circulating neurofilament light concentration, as a result of the treatment with Mas receptor agonist-- this is something that naturally follows and is a material property of the treatment with the claimed drug. Wherever/whenever a therapeutically effective amount of the Mas receptor agonist drug is used, there will necessarily be a reduction in neurofilament light concentration. Therefore, the instant claiming of neurofilament light is made obvious by the combination of the prior art.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention and one would have had reasonable expectation of success using a therapeutically effective amount of the treatment for Alzheimer’s of HAY in the method of detecting and treatment Alzheimer’s of BLENNOW using the Mas receptor agonist’s of HAY since the Mas receptor agonists/oligopeptides of HAY are shown to have promise for attenuating pain and behavioral signs in patients and reducing one or more symptoms of cognitive impairment including, for example, reduced attention, memory loss, psychomotor slowing, and diminished executive function (HAY, paragraph 0095, 0016, 0089).
The combination of BLENNOW and HAY above teaches of detecting and monitoring NFL over time before and after treatments for cognitive diseases and relating the level of NFL over time of multiple measurements to the risk of developing the neurodegenerative disease further increasing or decreasing (BLENNOW, paragraph 0109). And HAY teaches that Mas receptor agonists/oligopeptides in therapeutically effective amounts are shown to have promise for attenuating pain and behavioral signs in patients and reducing one or more symptoms of cognitive impairment including, for example, reduced attention, memory loss, psychomotor slowing, and diminished executive function (HAY, paragraph 0095, 0016, 0089, 0014, 0051, 0082).
Though BLENNOW and HAY make obvious the titrating of dose as amended to the claims dated 07/23/2026 in that no dosing/no treatment can read on it and therefore make the instant Claim 3 as a whole obvious, to expedite compact prosecution, BLENNOW and HAY do not teach of specifically titrating or adjusting the dose of Mas receptor agonist dose/therapeutically effective amount or administration frequency up for the cognitive disorder.
HAY2 is used to remedy this and teaches of a novel angiotensin-(1-7) glycosylated mas receptor agonist (PNA5) for treating vascular cognitive impairment (title and abstract). HAY2 specifically teaches of 3 weeks of systemic treatment (so of delivering multiple doses) with PNA5 via daily sub cutaneous injection in a model of VCID/HF rescues cognitive impairment and results in a sustained decrease in systemic and brain inflammation. The observed sustained reversal of cognitive dysfunction suggests that PNA5 may be a novel “first-in-class” therapy for the treatment of cognitive impairment in patients with VCID or conditions of chronic systemic inflammation and compromised brain blood flow (Page 17, column 2, last paragraph & Page 18, column 1, first paragraph). HAY2 also indicates that after treatment for 21 days, the patients shows up to 10 days of sustained cognitive protective effects and therefore that PNA5 (Mas receptor agonist) activation of the Mas receptor results in a dose-dependent inhibition of ROS(abstract) and that dosage is optimized and can be once weekly after sustained daily dosing and further optimized (Page 19, column 2, last paragraph).
It would have been obvious to one or ordinary skill in the art to increase dosage or dose again as is done in HAY2 with the Mas receptor agonist in the methods of BLENNOW and HAY due to the advantage the Mas receptor agonist has shown in only having effectiveness for 10 days of sustained cognitive protective effects after 21 days of dosing and therefore needing to readminister or optimize the increase of dosing (Page 19, column 2, last paragraph).
With respect to Claim 8, BLENNOW teaches of the invention as shown above for Claim 3, but does not teach of the claimed Mas receptor oligopeptide sequence.
HAY is used to remedy this and more specifically teaches of methods of using oligopeptides for treatment of diseases where cognitive dysfunction is present (abstract). Even further HAY teach that the oligopeptide treatment is a Mas receptor agonist (paragraph 0091), and that it has a sequence of A.sup.1-A.sup.2-A.sup.3-A.sup.4-A.sup.5-A.sup.6-A.sup.7-A.sup.8 (SEQ ID NO:1). HAY further teaches Asp-Arg-Val-Tyr-Ile-His-Pro, i.e., DRVYIHP (SEQ ID NO:2). Retro-inverso Ang-(1-7) (D-amino acids, C.fwdarw.N direction) is: DRVYIHP (SEQ ID NO:3). Retro Ang-(1-7) (L-amino acids, C.fwdarw.N direction) is: DRVYIHP (SEQ ID NO:4). And inverso Ang-(1-7) (D-amino acids, N.fwdarw.C direction) is: DRVYIHP ( SEQ ID NO:5). The use of D-amino acids in the context of inverso modified and retro-inverso modified Ang-(1-7) derivatives is not intended to be limiting on the use of D-amino amino acids in the oligopeptides. As discussed in more detail below, fewer than all of the amino acids in an Ang-(1-7) derivative may be D-amino acids (paragraph 0045), which are the same as the claimed SE IDs.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention and one would have had reasonable expectation of success using the oligopeptide Mas receptor agonist of HAY in the method of detecting and treatment Alzheimer’s of BLENNOW using the Mas receptor agonist’s of HAY since the Mas receptor agonists are show to have promise for attenuating pain and behavioral signs in patients and due the advantage that Mas receptor activation by agonist has for attenuating spatial memory and object recognition/so for improving cognitive impairment (HAY, paragraph 0095, 0016, 0089, 0007).
With respect to Claim 10, BLENNOW teaches of the invention as shown above for Claim 3, but does not teach of the claimed Mas receptor oligopeptide sequence.
HAY is used to remedy this and more specifically teaches of methods of using oligopeptides for treatment of diseases where cognitive dysfunction is present (abstract). Even further HAY teach that the oligopeptide treatment is a Mas receptor agonist (paragraph 0091), and that it has a sequence of A.sup.1-A.sup.2-A.sup.3-A.sup.4-A.sup.5-A.sup.6-A.sup.7-A.sup.8 (SEQ ID NO:1),
Where A.sup.1 is selected from the group consisting of aspartic acid, glutamic acid, alanine, and a derivative thereof; A.sup.2 is selected from the group consisting of arginine, histidine, lysine, and a derivative thereof; A.sup.3 is selected from the group consisting of valine, alanine, isoleucine, leucine, and a derivative thereof; A.sup.4 is selected from the group consisting of tyrosine, phenylalanine, tryptophan, and a derivative thereof; A.sup.5 is selected from the group consisting of isoleucine, valine, alanine, leucine, and a derivative thereof; A.sup.6 is selected from the group consisting of histidine, arginine, lysine, and a derivative thereof; A.sup.7 is selected from the group consisting of proline, glycine, serine, and a derivative thereof; and A.sup.8 can be present or absent, wherein when A.sup.8 is present, A.sup.8 is selected from the group consisting of serine, threonine, hydroxyproline, and a derivative thereof, provided (i) at least one of A.sup.1-A.sup.8 is optionally substituted with a mono- or di-carbohydrate; or (ii) when A.sup.8 is absent: (a) at least one of A.sup.1-A.sup.7 is substituted with a mono- or di-carbohydrate (saccharide)(paragraph 0046), (b) A.sup.7 is terminated with an amino group, or (c) a combination thereof (paragraph 0009). HAY further teaches of one of the A residues being glycosylated (paragraphs 0011-0013).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention and one would have had reasonable expectation of success using the oligopeptide Mas receptor agonist of HAY in the method of detecting and treatment Alzheimer’s of BLENNOW using the Mas receptor agonist’s of HAY since the Mas receptor agonists are show to have promise for attenuating pain and behavioral signs in patients (HAY, paragraph 0095, 0016, 0089).
With respect to Claim 11, BLENNOW teaches of the invention as shown above for Claim 10, but does not teach of the claimed Mas receptor oligopeptide sequence.
HAY is used to remedy this and more specifically teaches of methods of using oligopeptides for treatment of diseases where cognitive dysfunction is present (abstract). Even further HAY teach that the oligopeptide treatment is a Mas receptor agonist (paragraph 0091), and that it has a sequence of A.sup.1-A.sup.2-A.sup.3-A.sup.4-A.sup.5-A.sup.6-A.sup.7-A.sup.8 (SEQ ID NO:1).
HAY teaches that A.sup.8 can be present or absent, wherein when A.sup.8 is present, A.sup.8 is selected from the group consisting of serine, threonine, hydroxyproline, and a derivative thereof, provided (i) at least one of A.sup.1-A.sup.8 is optionally substituted with a mono- or di-carbohydrate (saccharide); or (ii) when A.sup.8 is absent: (a) at least one of A.sup.1-A.sup.7 is substituted with a mono- or di-carbohydrate (saccharide)(paragraph 0046), (b) A.sup.7 is terminated with an amino group, or (c) a combination thereof (paragraph 0009). HAY further teaches of one of the A residues being glycosylated (paragraphs 0011-0013).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention and one would have had reasonable expectation of success using the oligopeptide Mas receptor agonist of HAY in the method of detecting and treatment Alzheimer’s of BLENNOW using the Mas receptor agonist’s of HAY since the Mas receptor agonists are show to have promise for attenuating pain and behavioral signs in patients (HAY, paragraph 0095, 0016, 0089).
With respect to Claim 15, BLENNOW teaches of the invention as shown above for Claim 10, but does not teach of the claimed Mas receptor oligopeptide sequence.
HAY is used to remedy this and more specifically teaches of methods of using oligopeptides for treatment of diseases where cognitive dysfunction is present (abstract). Even further HAY teach that the oligopeptide treatment is a Mas receptor agonist (paragraph 0091), and that it has a sequence of A.sup.1-A.sup.2-A.sup.3-A.sup.4-A.sup.5-A.sup.6-A.sup.7-A.sup.8 (SEQ ID NO:1).
HAY teaches that A.sup.8 can be present or absent, wherein when A.sup.8 is present, A.sup.8 is selected from the group consisting of serine, threonine, hydroxyproline, and a derivative thereof, provided (i) at least one of A.sup.1-A.sup.8 is optionally substituted with a mono- or di-carbohydrate (saccharide); or (ii) when A.sup.8 is absent: (a) at least one of A.sup.1-A.sup.7 is substituted with a mono- or di-carbohydrate (saccharide)(paragraph 0046), (b) A.sup.7 is terminated with an amino group, or (c) a combination thereof (paragraph 0009). HAY further teaches of one of the A residues being glycosylated (paragraphs 0011-0013) and even further that specifically A.sup.7 or A.sup.8 can be glycosylated glucose or lactose (paragraph 0011, Claim 8).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention and one would have had reasonable expectation of success using the oligopeptide Mas receptor agonist of HAY in the method of detecting and treatment Alzheimer’s of BLENNOW using the Mas receptor agonist’s of HAY since the Mas receptor agonists are show to have promise for attenuating pain and behavioral signs in patients (HAY, paragraph 0095, 0016, 0089).
With respect to Claim 17, BLENNOW teaches of the invention as shown above for Claim 15, but does not teach of the claimed Mas receptor oligopeptide sequence with the claimed A.sup.7 or A.sup.8 amino group specifications.
HAY is used to remedy this and more specifically teaches of methods of using oligopeptides for treatment of diseases where cognitive dysfunction is present (abstract). Even further HAY teach that the oligopeptide treatment is a Mas receptor agonist (paragraph 0091), and that it has a sequence of A.sup.1-A.sup.2-A.sup.3-A.sup.4-A.sup.5-A.sup.6-A.sup.7-A.sup.8 (SEQ ID NO:1).
HAY further teaches that A.sup.8 can be present or absent, wherein when A.sup.8 is present, A.sup.8 is selected from the amino groups consisting of serine, threonine, hydroxyproline, and a derivative thereof, provided (i) at least one of A.sup.1-A.sup.8 is optionally substituted with a mono- or di-carbohydrate (saccharide); or (ii) when A.sup.8 is absent: (a) at least one of A.sup.1-A.sup.7 is substituted with a mono- or di-carbohydrate (saccharide)(paragraph 0046), (b) A.sup.7 is terminated with an amino group, or (c) a combination thereof (paragraph 0009). HAY further teaches of one of the A residues being glycosylated (paragraphs 0011-0013) and even further that specifically A.sup.7 or A.sup.8 can be glycosylated glucose or lactose (paragraph 0011, Claim 8).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention and one would have had reasonable expectation of success using the A.sup.7 or A.sup.8 amino terminated oligopeptide Mas receptor agonist of HAY in the method of detecting and treatment Alzheimer’s of BLENNOW using the Mas receptor agonist’s of HAY since the Mas receptor agonists are show to have promise for attenuating pain and behavioral signs in patients (HAY, paragraph 0095, 0016, 0089).
With respect to Claim 18, BLENNOW teaches of the invention as shown above for Claim 3, but does not teach of the claimed Mas receptor oligopeptide sequence with the claimed A.sup.7 or A.sup.8 glycosylated serine group specifications.
HAY is used to remedy this and more specifically teaches of methods of using oligopeptides for treatment of diseases where cognitive dysfunction is present (abstract). Even further HAY teach that the oligopeptide treatment is a Mas receptor agonist (paragraph 0091), and that it has a sequence of A.sup.1-A.sup.2-A.sup.3-A.sup.4-A.sup.5-A.sup.6-A.sup.7-A.sup.8 (SEQ ID NO:1).
HAY further teaches that A.sup.8 can be present or absent, wherein when A.sup.8 is present, A.sup.8 is selected from the amino groups consisting of serine, threonine, hydroxyproline, and a derivative thereof, provided (i) at least one of A.sup.1-A.sup.8 is optionally substituted with a mono- or di-carbohydrate (saccharide); or (ii) when A.sup.8 is absent: (a) at least one of A.sup.1-A.sup.7 is substituted with a mono- or di-carbohydrate (saccharide)(paragraph 0046), (b) A.sup.7 is terminated with an amino group, or (c) a combination thereof (paragraph 0009). HAY further teaches of one of the A residues being glycosylated (paragraphs 0011-0013) and even further that specifically A.sup.7 or A.sup.8 can be glycosylated serine (paragraph 0011-0012).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention and one would have had reasonable expectation of success using the A.sup.7 or A.sup.8 glycosylated serine terminated oligopeptide Mas receptor agonist of HAY in the method of detecting and treatment Alzheimer’s of BLENNOW using the Mas receptor agonist’s of HAY since the Mas receptor agonists are show to have promise for attenuating pain and behavioral signs in patients (HAY, paragraph 0095, 0016, 0089).
With respect to Claim 19, BLENNOW teaches of the invention as shown above for Claim 18, but does not teach of the claimed Mas receptor oligopeptide sequence with the claimed A.sup.7 or A.sup.8 glycosylated amino with glucose or lactose group specifications.
HAY is used to remedy this and more specifically teaches of methods of using oligopeptides for treatment of diseases where cognitive dysfunction is present (abstract). Even further HAY teach that the oligopeptide treatment is a Mas receptor agonist (paragraph 0091), and that it has a sequence of A.sup.1-A.sup.2-A.sup.3-A.sup.4-A.sup.5-A.sup.6-A.sup.7-A.sup.8 (SEQ ID NO:1).
HAY further teaches that A.sup.8 can be present or absent, wherein when A.sup.8 is present, A.sup.8 is selected from the amino groups consisting of serine, threonine, hydroxyproline, and a derivative thereof, provided (i) at least one of A.sup.1-A.sup.8 is optionally substituted with a mono- or di-carbohydrate (saccharide); or (ii) when A.sup.8 is absent: (a) at least one of A.sup.1-A.sup.7 is substituted with a mono- or di-carbohydrate (saccharide)(paragraph 0046), (b) A.sup.7 is terminated with an amino group, or (c) a combination thereof (paragraph 0009). HAY further teaches of one of the A residues being glycosylated (paragraphs 0011-0013) and even further that specifically A.sup.7 or A.sup.8 can be glycosylated glucose or lactose (paragraph 0011, Claim 8).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention and one would have had reasonable expectation of success using the A.sup.7 or A.sup.8 glycosylated amino glucose or lactose terminated oligopeptide Mas receptor agonist of HAY in the method of detecting and treatment Alzheimer’s of BLENNOW using the Mas receptor agonist’s of HAY since the Mas receptor agonists are show to have promise for attenuating pain and behavioral signs in patients (HAY, paragraph 0095, 0016, 0089).
With respect to Claim 20, BLENNOW teaches of the invention as shown above for Claim 18, but does not teach of the claimed Mas receptor oligopeptide sequence with the claimed A.sup.7 or A.sup.8 amino group specifications.
HAY is used to remedy this and more specifically teaches of methods of using oligopeptides for treatment of diseases where cognitive dysfunction is present (abstract). Even further HAY teach that the oligopeptide treatment is a Mas receptor agonist (paragraph 0091), and that it has a sequence of A.sup.1-A.sup.2-A.sup.3-A.sup.4-A.sup.5-A.sup.6-A.sup.7-A.sup.8 (SEQ ID NO:1).
HAY further teaches that A.sup.8 can be present or absent, wherein when A.sup.8 is present, A.sup.8 is selected from the amino groups consisting of serine, threonine, hydroxyproline, and a derivative thereof, provided (i) at least one of A.sup.1-A.sup.8 is optionally substituted with a mono- or di-carbohydrate (saccharide); or (ii) when A.sup.8 is absent: (a) at least one of A.sup.1-A.sup.7 is substituted with a mono- or di-carbohydrate (saccharide)(paragraph 0046), (b) A.sup.7 is terminated with an amino group, or (c) a combination thereof (paragraph 0009). HAY further teaches of one of the A residues being glycosylated (paragraphs 0011-0013) and even further that specifically A.sup.7 or A.sup.8 can be glycosylated glucose or lactose (paragraph 0011, Claim 8).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention and one would have had reasonable expectation of success using the A.sup.7 or A.sup.8 amino terminated oligopeptide Mas receptor agonist of HAY in the method of detecting and treatment Alzheimer’s of BLENNOW using the Mas receptor agonist’s of HAY since the Mas receptor agonists are show to have promise for attenuating pain and behavioral signs in patients (HAY, paragraph 0095, 0016, 0089).
With respect to Claim 21, BLENNOW teaches of the invention as shown above for Claim 10, but does not teach of the claimed Mas receptor oligopeptide PN-A5.
HAY is used to remedy this and more specifically teaches of methods of using oligopeptides for treatment of diseases where cognitive dysfunction is present (abstract). Even further HAY teach that the oligopeptide treatment is a Mas receptor agonist (paragraph 0091), which is PN-A5 (paragraph 0110, 0113).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention and one would have had reasonable expectation of success using the oligopeptide Mas receptor agonist, PN-A5 of HAY in the method of detecting and treatment Alzheimer’s of BLENNOW using the Mas receptor agonist’s of HAY since the Mas receptor agonists are show to have promise for attenuating pain and behavioral signs in patients (HAY, paragraph 0095, 0016, 0089).
With respect to Claim 22, BLENNOW teaches of the invention as shown above for Claim 10, but does not teach of the claimed Mas receptor oligopeptide PN-A6.
HAY is used to remedy this and more specifically teaches of methods of using oligopeptides for treatment of diseases where cognitive dysfunction is present (abstract). Even further HAY teach that the oligopeptide treatment is a Mas receptor agonist (paragraph 0091), which is PN-A6 (paragraph 0078, Table 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention and one would have had reasonable expectation of success using the oligopeptide Mas receptor agonist, PN-A6 of HAY in the method of detecting and treatment Alzheimer’s of BLENNOW using the Mas receptor agonist’s of HAY since the Mas receptor agonists are show to have promise for attenuating pain and behavioral signs in patients (HAY, paragraph 0095, 0016, 0089).
With respect to Claim 23, BLENNOW teaches of the invention as shown above for Claim 10, but does not teach of the claimed Mas receptor oligopeptide containing at least one D-amino acid.
HAY is used to remedy this and more specifically teaches of methods of using oligopeptides for treatment of diseases where cognitive dysfunction is present (abstract). Even further HAY teach that the oligopeptide treatment is a Mas receptor agonist (paragraph 0091), which contains at least one D-amino acid (paragraph 0045, 0049, 0059-0060).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention and one would have had reasonable expectation of success using the oligopeptide Mas receptor agonist, with D- amino acids therein of HAY in the method of detecting and treatment Alzheimer’s of BLENNOW using the Mas receptor agonist’s of HAY since the Mas receptor agonists are show to have promise for attenuating pain and behavioral signs in patients (HAY, paragraph 0095, 0016, 0089).
With respect to Claim 56, BLENNOW teaches that pre-symptomatic carriers have a measured level for a control of 16.7 pg.ml of Nfl in serum (paragraph 0184). This reads on “about,” 25 pg/ml through broadest reasonable interpretation. For symptomatic carriers, it teaches that the control level for serum Nfl is 46 pg/ml (Figure 4). Since anything measured over the reference level indicates disease, both these values make the claimed 25 pg/ml level obvious to one of ordinary skill in the art before the effective filing date of the instant invention to be indicative for disease.
With respect to Claim 57, BLENNOW teaches that pre-symptomatic carriers have a measured level for a control of 16.7 pg.ml of Nfl in serum (paragraph 0184). BLENNOW also teaches of measuring Nfl levels of, “about 75 pg/ml,” as claimed (See Figure 3). For symptomatic carriers, it teaches that the control level for serum Nfl is 46 pg/ml (Figure 4). Since anything measured over the reference level indicates disease, both these values make the claimed 25 pg/ml level obvious to one of ordinary skill in the art before the effective filing date of the instant invention to be indicative for disease.
Response to Arguments
Applicant's arguments filed 07/23/2026 have been fully considered but they are not persuasive.
The prior objections were overcome due to amendments made 07/23/2026, however a new one was added as shown above.
Post interview dated 07/21/2026 the examiner has further considered the claims with respect to amendments made 07/23/2026 and the prior art in light of them. Though the examiner initially agreed with applicant’s representative that no dose adjustment wat taught, during the further consideration during examination time which is much more substantive than time given for interviews the examiner noticed an interpretation that the dosage adjustment in Claim 3 is left open to through broadest reasonable interpretation, which is no treatment for the second dose, or stoppage of treatment which can read on the claimed “reduced,” dosing of a treatment.
The examiner has also added a third reference, in hopes of expediting compact prosecution showing how a reference can read on increasing dosage of Mas receptor agonist through broadest reasonable interpretation.
The examiner understands that two of the cited prior art pieces are by the instant applicant however effectively predate the instant priority date of the instant application. The examiner has briefly reviewed the instant specification and does not see a very clear cut suggestion for amendment which the combination of prior arts, including the 1 prior art which is not by the instant inventor. As applicant likely knows their instant filing and it’s contents in comparison to the instantly cited prior art best, it is possible that they know of contents not found in the pieces of prior art used, which could be added to the instant claims. The examiner notes that though the BLENNOW reference does not teach of the claimed treatment and adjusting the does of specifically a Mas receptor agonist as done in the two claimed up or down options, the second and third references do make this obvious. Even though, they do not do them specifically based on NFL concentration, but instead do the treatment based on a cognitive condition, which is also mentioned in BLENNOW, so all the references are tied together to make the instant claimed obvious. The examiner notes that the prior art used in the instant rejection is the best found prior art.
All claims remain rejected.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
McQUISTON in US 20190242906 teaches methods for diagnosis patients who have cognitive or head injuries (abstract) wherein Nfl is used as a biomarker (paragraph 0575), and even further teaches of treating the patient (paragraph 0054-0055).
HAY3 in US 20180200326 teaches of oligopeptides treatments, in particular, Ang-(1-7) derivatives, and methods for using and producing the same. In one particular embodiment, oligopeptides of the invention have higher blood-brain barrier penetration and/or in vivo half-life compared to the native Ang-(1-7), thereby allowing oligopeptides of the invention to be used in a wide variety of clinical applications including in treatment of cognitive dysfunction and/or traumatic brain injury (abstract), but also for treatment of Alzheimer’s (paragraph 0014). HAY3 also teaches of the treatment compounds have the claimed sequences of PN-A5 and PN-A6 (paragraphs 0031-0032), and all other residue groups claimed (paragraph 0033, 0036, paragraphs 0008-0012).
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/REBECCA M FRITCHMAN/Primary Examiner, Art Unit 1758
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