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 Final Office action based on the 18/039641 application response filed on 03/03/2026.
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.
Claim Objections
Claim 3 is objected to because of the following informalities:
In the preamble of Claim 3, it states, “treating a subject diagnosed as having a cognitive impairment,” however in the claim body the word diagnosis is not used anywhere. Instead, “identifying,” is used. Similarly, “treating,” is in the preamble, but not about “treating,” is in the claim body. Though it is understood what applicant means here the same terminology should be used in preamble and claim body to prevent confusion. Appropriate correction is required.
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.
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) 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 the in 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 (paragraph 0109), and of monitoring a patient using these tactics including monitoring of a prophylactic treatment (paragraph 0108, 0036).
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 does not teach of administering a therapeutic agent which is the claimed Mas receptor agonist and 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), and further wherein the disease is Alzheimer’s (paragraph 0016, 0083, 0089). Even further HAY teach that the oligopeptide treatment is a Mas receptor agonist (paragraph 0091), and that a therapeutically effective amount of the treatment is administered (paragraph 0014, 0051, 0082).
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 are show to have promise for attenuating pain and behavioral signs in patients (HAY, paragraph 0095, 0016, 0089).
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). 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.
Response to Arguments
Applicant's arguments filed 03/03/2026 have been fully considered but they are not persuasive.
The prior objections were overcome due to amendments made 03/03/2026, however a new one was added as shown above.
The prior 112 (b) rejections are overcome due to amendments dated 03/03/2026.
The prior 101 rejections are overcome due to amendments dated 03/03/2026 as the claimed treatment is now required to always happen within the boundaries or the claim and it is considered to be particular and specific treatment and to therefore practically apply the judicial exception.
The prior 102 (a)(1) and 102 (a)(2) rejections are dropped, since the claims which were rejected under this statute were cancelled in amendments dated 03/03/2026.
The 103 rejection is maintained.
With respect to BLENNOW and HAY—applicant argues that neither reference individually teaches of the whole claimed method of detecting NFL above a threshold as being diagnostic for cognitive impairment, and then treating it with Mas receptor agonist as claimed.
In response to this, applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
More pointedly, applicant argues that neither reference teaches that the claimed treatment therapy, “reduces circulating neurofilament light concentration,” nor does the prior art reference/s teach that “neurofilament light reduction would serve as a therapeutic endpoint of such treatment.” Further applicant argues that “the conclusion of obviousness therefore depends upon knowledge derived from Applicant’s disclosure rather than the teachings of the prior art.”
The examiner disagrees with the above arguments by applicant.
Though--- the examiner understands that no reference specifically calls out that treating with a Mas receptor agonist-- “reduces circulating neurofilament light concentration,” 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- this is made obvious by the combination of the prior art above. And the fact that both prior art references deal with cognitive impairment ties them adequately together.
Further--- this is particularly the case as nothing is claimed about a second measurement or NFL or determination after the administration of therapeutically effective amount of Mas receptor agonist is performed. Even as claimed--- the resulting reduction in NFL, is something that naturally follows as result of a treatment and not an additional claimed step. Even if claimed as an additional step, it is unlikely that this would help matters as checking the effects of a treatment is commonly done in the art.
The examiner notes that nothing is claimed about ---“neurofilament light reduction would serve as a therapeutic endpoint of such treatment.” It is not clear what is meant by this argument, as also it is not commensurate in scope with the claims as nothing is claimed about this.
Further, with respect to applicant’s argument that “the conclusion of obviousness therefore depends upon knowledge derived from Applicant’s disclosure rather than the teachings of the prior art,” the examiner disagrees. The examiners conclusion is obviousness is based on what is taught by the prior art and also by what the material properties of the treatment compound would necessarily do (decrease NFL), since this would be done/is done because of it’s material properties.
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).
Conclusion
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.
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).
HAY2 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). HAY 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).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REBECCA M FRITCHMAN whose telephone number is (303)297-4344. The examiner can normally be reached 9:30-4:30 MT Monday-Friday.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maris Kessel can be reached on 571-270-7698. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/REBECCA M FRITCHMAN/Primary Examiner, Art Unit 1758
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