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 the Non-Final Office Action based on application 18/54460 RCE filed 04/13/2026.
Claims 27-28, 31-32, 38-39 & 43-45 are pending.
Claims 1-26, 29-30, 33-37, & 40-42 have been cancelled.
Claims 27, 31-32, 38-39 are withdrawn from consideration
Claims 28 & 43-45 have been elected and fully considered.
Claims 43-45 were newly added.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 04/13/2026 has been entered.
Claim Rejections - 35 USC § 112
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 28 & 43-45 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
With respect to Claim 28, it claims contacting steps which are seemingly are the same. The first states, “contacting a first portion of the sample to a first assay plate coated with anti-CEL capture antibodies, and contacting a second potion of the sample to a second assay plate coated with anti-MG-H1 capture antibodies.”
The second states, “contacting the first assay plate with anti-CEL detection antibodies and contacting the second assay plate with anti-MG-HA detection antibodies.
While it’s clear that applicant intends capture antibodies and detection antibodies to be different entities, it is unclear when the detection antibodies are added/contacted with the assay plates, if applicant means that they are contacted with the plate that is already coated with the capture antibodies or not. Correction is required.
Further for Claim 28, with respect to the claimed “capture antibodies,” and “detection antibodies,” and even more specifically with respect to these claimed terms for specifically anti-MG-H1(antibody for methylglyoxal hydroimidazolone) and for anti-CEL (antibody for carboxyethyl lysine), the examiner notes that the only place in the instant PGPUB specification where the terms “capture antibody,” and “detection antibodies,” are shown is in paragraph 0162. In this paragraph, capture antibodies are only mentioned with respect to collagen XVII and detection antibodies are mentioned for CEL, CML and pentosidine. Therefore, capture antibodies are not mentioned at all in the specification for the instantly claimed MG-H1 or CEL. Detection antibodies are not mentioned at all in the instant specification for MG-H1.
The instant specification also includes disclosure of “primary,” and “secondary,” antibodies in instant PGPUB paragraph 0165), however these also are not specific to MG-H1 and these terms are not what is claimed.
Further, instant PGPBUB Figure 24 and the associated description in PGPUB paragraph 0053, shows chemical formulas of glycotoxins (pentosidine, CEL, CML, and MG-H1), glycotoxin-protein complexes (protein-pentosidine, protein-CEL, protein-CML, and protein-MG-H1), and collagen XVII-CEL, along with the binding states of the proteins to the formulas. Though Figure 24 does in fact show binding of MG-H1 binding to a protein, it does not show MG-H1 binding to an antibody. While antibodies are in fact proteins( and more specifically glycoproteins), this still does not show disclosure of MG-H1 binding to an antibody (which is a species of the genus of proteins). Even further, this does not bring clarity to what is considered a detection antibody for MG-H1 as claimed versus what is considered a capture antibody for MG-H1, nor does it bring clarity to what specifically a capture antibody is for CEL. Therefore, what exactly is considered to be a capture antibody versus detection antibody for CEL and MG-H1 as claimed is unclear.
Claim 43-45 are rejected by virtue of being dependent on Claim 28.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 28 & 43-45 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 28, with respect to the claimed “capture antibodies,” and “detection antibodies,” and even more specifically with respect to these claimed terms for specifically anti-MG-H1(antibody for methylglyoxal hydroimidazolone) and for anti-CEL (antibody for carboxyethyl lysine), the examiner notes that the only place in the instant PGPUB specification where the terms “capture antibody,” and “detection antibodies,” are shown is in paragraph 0162. In this paragraph, capture antibodies are only mentioned with respect to collagen XVII and detection antibodies are mentioned for CEL, CML and pentosidine. Therefore, capture antibodies are not mentioned at all in the specification for the instantly claimed MG-H1 or CEL, which is what is claimed. Detection antibodies are not mentioned at all in the instant specification for MG-H1, again which is what is claimed.
The instant specification also includes disclosure of “primary,” and “secondary,” antibodies in instant PGPUB paragraph 0165), however these also are not specific to MG-H1 and these terms are not what is claimed.
Further, instant PGPBUB Figure 24 and the associated description in PGPUB paragraph 0053, shows chemical formulas of glycotoxins (pentosidine, CEL, CML, and MG-H1), glycotoxin-protein complexes (protein-pentosidine, protein-CEL, protein-CML, and protein-MG-H1), and collagen XVII-CEL, along with the binding states of the proteins to the formulas. Though Figure 24 does in fact show binding of MG-H1 binding to a protein, it does not show MG-H1 binding to an antibody. While antibodies are in fact proteins (and more specifically glycoproteins), this still does not show disclosure of MG-H1 binding to an antibody (which is a species of the genus of proteins).
Therefore, the instant claiming of both capture and detection antibodies, for specifically each of MG-H1 and CEL is new matter, which was introduced at a time after the initial filing, and that was not disclosed in the instant specification as originally filed.
Claims 43-45 are rejected by virtue of their dependency on Claim 28.
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 ofmatter, or any new and useful improvement thereof, may obtain a patent therefor, subject to theconditions and requirements of this title.
Claims 28 & 43-45 are rejected under 101 as they are directed to non-statutory subject matter.
Through 101, inquiry analysis:
Step 1: Are the claims directed to a statutory category of invention?
Yes, independent claims 28, 44 & 45 are drawn towards a statutory category, method.
Step 2A, Prong One: Does the claim involve a Judicial Exception?
Yes. Claim 28 involves a judicial exception of a law of nature which is a natural correlation which is the amount and ratio of CEL and/ to MG-H1 with the correlation or diagnosis (presence) of a neurodegenerative disease. As claimed applicant calls them a composite biomarker, but as claimed it seems they are measured individually.
Though Claim 28 does not use the word diagnosis/diagnosing, the last step in the claim says a cut-off ratio “indicates,” presence of the neurodegenerative disease, and the “measuring,” of a neurodegenerative disease as claimed in the preamble is the same as diagnosing. Therefore, though the diagnosing is not explicitly in the claims, it is still implicitly there.
Claim 28 also includes steps which are “calculating,” ratios and “comparing,” to cutoff values. The calculating is a mathematical process and the comparing is a mental process. These are both abstract idea judicial exceptions.
See MPEP 2106.04 (a)(2) & MPEP 2106.04(b)
Claims 44 & 45 are technically independent, however they both require determining a ratio and comparing to the cutoff value of 11.53, “according Claim 28,” so these claims include the same judicial exceptions as shown for Claim 28.
Step 2A, Prong Two: Do the claims practically apply the judicial exception?
No, there are no features instantly claimed which practically apply the claimed natural correlation or abstract idea judicial exceptions.
Independent Claim 28 includes the additional steps of
“extracting blood,”
“preparing a sample of plasma from the extracted blood,”
contacting the sample with a first and second assay plate having anti-CEL and anti-MG-H1, capture antibodies coated on them respectively,
contacting the first and second assay plate with anti-CEL and anti-MG-H1, detection antibodies, and
detecting binding by measuring color changes as optical density values.
With respect to the above, applicant has added more detail to the claims, however, none of what is claimed practically applies the judicial exceptions. Nothing is done after the diagnosis to practically apply. In fact, in the claims, nothing is done after the diagnosis or indication of neurodegenerative disease occurs.
Further, the claimed, “extracting,” “preparing,” “contacting” (to a plate which has anti-CEL and anti-MG-H1, antibodies bound thereto with both detection and capture antibodies), and detecting binding through color changes and optical density, are all steps are all performed as mere data gathering through to accomplish the judicial exception and therefore are considered insignificant extra-solution activity. See MPEP 2106.05(g).
In independent Claim 44, it is added that a treatment is administered if a specific ratio is found during a comparison. The comparison itself is a mental process so abstract idea judicial exception. As claimed for claim 44, the treatment is akin to “administering a suitable medication to a patient.” This administration step is not particular, and is instead merely instructions to “apply” the exception in a generic way. Thus, the administration step does not integrate the mental analysis step into a practical application. See MPEP 2106.04(d)(2) a, which recites the above paragraph.
In independent Claim 45, “diagnosing,” is again claimed and it is specific to a ratio being found during a comparison. Both the diagnosing based on a number/the ratio and the comparison are judicial exceptions. Respectively these are law of nature and abstract idea judicial exceptions.
Step 2B: Do the claims add significantly more to the judicial exception?
There are no features instantly claimed which result in significantly more than the claimed natural correlation or abstract idea.
The claimed, “extracting,” “preparing,” “contacting” (to a plate which has anti-CEL and anti-MG-H1, antibodies bound thereto with both detection and capture antibodies), and detecting binding through color changes and optical density, as outlined in step 2A/2 above are all things which are well understood, routine and conventional (WURC) in the art and therefore do not add significantly more.
The claims still read somewhat similarly to USPTO eligibility example 29 (Julitis claims), Claim 2, which was found ineligible. Nothing as claimed, distinguishes from well understood, routine, and conventional activity engaged in by scientists prior to applicant’s invention, and at the time the application was filed, e.g., the routine and conventional techniques of detecting using an antibody to that protein.
Further, it is well established that the mere physical or tangible nature of additional elements such as the obtaining and detecting steps does not automatically confer eligibility on a claim directed to an abstract idea (see, e.g., Alice Corp. v. CLS Bank Int’l, 134 S.Ct. 2347, 2358-59 (2014)).
Independent claims 44 & 45 do not add anything which changes the above. Claim 45 does require a treatment, however at the generality the treatment is claimed it could be almost anything, so it is also considered.
That the above is WURC is evidenced by:
HANSSEN in Measurement of advanced glycation endproducts in human plasma by ultra- performance liquid chromatography tandem mass spectrometry
HANSSEN teaches that they determine the amount of carboxyethyl lysine (CEL), and the amount of MG-H1. HANSSEN further teaches that levels measured are compared to healthy controls (Page 45, first two paragraphs). HANSSEN also teaches that though UPLC MS is preferred for determining the amounts of these compounds, that ELISA (which uses enzymatic reactions with anti-the compound detected antibodies) has also been used for the determination of their amounts (Page 54, paragraph 1).
HANSSEN teaches of using blood samples for the measurements and more specifically of using plasma sample and specifically of measuring CEL and MG-H1 in it (Page 46, last paragraph).
HANSSEN also teaches of determination of the amount/accumulation of these AGE compounds (which include MG-H1 and CEL) (Page 10, paragraph 1, line 8) and of detecting the accumulation of them through fluorescence and autofluorescence (Page 14, paragraph 1). HANSSEN further teaches of measuring the AGEs in comparison to healthy controls/a threshold wherein an increase compared to control indicates disease--- and measuring the two compounds together also show the claimed composite biomarker (paragraph 54, last paragraph, last two lines & Page 53, Figure 2B.5 & Page 53).
GRUBER in US 20200150131
GRUBER teaches that tissue samples are obtained from patients with various neurodegenerative diseases (paragraph 0113, 0112), or using cell extraction reagents and microtiter plates (paragraph 0065), which are ELISA plates with antibodies specific to the compounds detected thereon (paragraph 0069-0076) and further of extracting/separating the blood sample into serum and plasma (paragraph 0045). GRUBER even further teaches of coating 1 antibody to the plate and then using a secondary antibody, HRP-goat anti-mouse Fc for detection. Therefore, this makes using the claimed capture antibody and detection antibody as claimed obvious (paragraph 0069) and specifically that more than 1, “plates,” can be used(paragraph 0065) and that each of the plates has multiple wells which can be treated the same of differently (paragraph 0069-0074). GRUBER also teaches of using optical imaging for the plates (paragraph 0061).
ROGERS in US 20090304577
ROGERS teaches of methods for diagnosis and treatment of Alzheimers (paragraph 0103), and specifically of detecting advanced glycation products for this (paragraphs 0130-0135). ROGERS even further teaches of detecting color changes which indicates enzymatic changes for the antibody and target binding of the instant invention (paragraph 0288) and further of detecting on an optical plate (paragraph 0291) and of making optical density readings (Table 1 & 2).
See MPEP 2106.04 & 2106.05, 2106.05(d) which deals with what is considered “Well-Understood, Routine and Conventional”.
Nothing in the dependent claim changes the matters above.
Claim 43 specifies what the neurodegenerative disease is, however the disease is part of the claimed law of nature natural correlation/diagnosis itself and therefore part of the claimed judicial exception, so nothing is added here which practically applies nor which adds significantly more is claimed.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 28 & 43-45 are rejected under 35 U.S.C.103 as being obvious over HANSSEN in Measurement of advanced glycation endproducts in human plasma by ultra- performance liquid chromatography tandem mass spectrometry in view of TRELLU in Impairment of glyoxalase-1, an advanced glycation end-product detoxifying enzyme, induced by inflammation in age-related osteoarthritis and further in view of GRUBER in US 20200150131 and further in view of ROGERS in US 20090304577.
With respect to Claim 28, HANSSEN teaches of a method of measuring advanced glycation products/AGEs (title) in which the AGEs are known to be related to neurodegenerative diseases/disorders (Page 172, paragraphs 1 & 2).
HANSSEN teaches that they determine the amount of carboxyethyl lysine (CEL), and the amount of MG-H1. HANSSEN further teaches that levels measured are compared to healthy controls (Page 45, first two paragraphs). HANSSEN also teaches that though UPLC MS is preferred for determining the amounts of these compounds, that ELISA (which uses enzymatic reactions with anti-the compound detected antibodies) has also been used for the determination of their amounts (Page 54, paragraph 1).
HANSSEN teaches of using blood samples for the measurements and more specifically of using plasma sample and specifically of measuring CEL and MG-H1 in it (Page 46, last paragraph).
HANSSEN also teaches of determination of the amount/accumulation of these AGE compounds (which include MG-H1 and CEL) (Page 10, paragraph 1, line 8) and of detecting the accumulation of them through fluorescence and autofluorescence (Page 14, paragraph 1). HANSSEN further teaches of measuring the AGEs in comparison to healthy controls/a threshold wherein an increase compared to control indicates disease--- and measuring the two compounds together also show the claimed composite biomarker (paragraph 54, last paragraph, last two lines & Page 53, Figure 2B.5 & Page 53). The claimed cut-off values would follow naturally if a neurodegenerative disease is present, as this is how diagnostic science works.
HANSSEN does not teach specifically of determining the ratio of M-H1 specifically to CEL nor of measurement of optical density.
TRELLU is used to remedy this and more specifically teach of measuring accumulation of AGEs (abstract). TRELLU further teach of measuring CEL and MG-H1 (Page 2, column 1, first paragraph) and of measuring accumulation(abstract). TRELLU further teaches that all measurements of AGEs are expressed in a ratio with lysine (CEL) products (Page 3, column 2, paragraph 2, last two lines) (which reads on claimed ratio).
TRELLU also teaches of making spectrophotometric measurements (Page 4, column 2, lines 1-3). Spectrophotometry measures optical density and color change.
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 to measure the accumulation ratio as is done in TRELLU in the method of HANSSEN due to the need in the art for better studies/analysis on AGE accumulation (TRELLU, page 1, column 2, last paragraph, Page 2, column 1, first paragraph) and it would have been obvious to one of ordinary skill in the art to measure before the effective filing date the optical density using spectrophotometry as is done in TRELLU in the method of HANSSEN due to the advantage this offers for measuring concentrations of compounds (TRELLU, Page 3, column 2, last paragraph).
HANSSEN and TRELLU do not teach of binding anti- MG-H1 and CEL antibody to multiple plates for detection. Further, if the claimed extracting step is still unclear, GRUBER is also used to remedy this.
GRUBER teaches of a method of making diagnoses using advanced glycation end products and antibodies thereof (abstract). GRUBER teaches that these compounds are used to diagnose Alzheimer’s and Parkinson’s diseases (paragraph 0032-0035). GRUBER more specifically teaches of the advanced glycation end (AGE) products being neurodegenerative related (paragraph 0002), and of the compounds which are AGE including carboxyethylysine (CEL) (paragraph 0004, 0022) and that the AGEs form a reaction with methyl glyoxal (paragraph 0004, 0114).
Specifically, GRUBER teaches that tissue samples are obtained from patients with various neurodegenerative diseases (paragraph 0113, 0112), or using cell extraction reagents and microtiter plates (paragraph 0065), which are ELISA plates with antibodies specific to the compounds detected thereon (paragraph 0069-0076) and further of extracting/separating the blood sample into serum and plasma (paragraph 0045). GRUBER even further teaches of coating 1 antibody to the plate and then using a secondary antibody, HRP-goat anti-mouse Fc for detection. Therefore, this makes using the claimed capture antibody and detection antibody as claimed obvious (paragraph 0069) and specifically that more than 1, “plates,” can be used(paragraph 0065) and that each of the plates has multiple wells which can be treated the same of differently (paragraph 0069-0074). GRUBER also teaches of using optical imaging for the plates (paragraph 0061).
While GRUBER focuses their examples on CML (carboxymethyllysine), GRUBER teaches that carboxyethyllysine (CEL)can be used instead (paragraph 0022) and that antibodies against carboxyethylysine can be used on the plates which would be anti-CEL antibodies. GRUBER also teaches that any anti-AGE (advanced glycation product) antibody that binds to and AGE product/protein can be used (paragraph 0050- 0051). This makes using anti-MG-H1 antibody obvious as well since both TRELLU and SCHEIJEN teach of MG-H1 as an AGE product.
GRUBER further teaches of detecting increased level of the AGEs (which would include carboxyethyllysine and MGH1 (though this one is not taught in GRUBER)) are part of and that the increased level are recognized as markers of disease (GRUBER, paragraph 0010), and of measuring accumulation of the AGEs and ratios thereof (GRUBER, paragraph 0003, 0043-0044). GRUBER also teaches of measuring ratios AGE’s to other AGEs (paragraph 0014, 0038, 0040-0041, 0044).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention and there would have been reasonable expectation of success to bind anti-AGE antibodies of AGE compounds to a plate to detect the levels of the compounds in a sample and diagnose neurodegenerative disease therefrom as is done in GRUBER in the methods of TRELLU And HANSSEN due to the fact that AGE levels are an accepted marker of diseases so there is expected success (GRUBER, paragraph 0010) and due to the advantages anti-AGE based diagnostics offer as being a minimally invasive and simple test which can be carried out in a doctors office (GRUBER, paragraph 0038).
If optical density detection and color change by enzymatic reaction is not clear to one of ordinary skill from HANSSEN, TRELLU, and GRUBER, ROGERS is used to remedy this.
ROGERS teaches of methods for diagnosis and treatment of Alzheimers (paragraph 0103), and specifically of detecting advanced glycation products for this (paragraphs 0130-0135). ROGERS even further teaches of detecting color changes which indicates enzymatic changes for the antibody and target binding of the instant invention (paragraph 0288) and further of detecting on an optical plate (paragraph 0291) and of making optical density readings (Table 1 & 2).
Therefore, from the teachings above, it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to detect the claimed MG-H1 and CEL together, use and assay plate with the claimed anbodies bound to, then detect a color change and make optical density readings as is done in ROGERS in the methods of HANSSEN, TRELLU, and GRUBER due to the advantages these methods show for indicating binding and since enzymatic color change is measurable spectrophotometrically (Table 1, paragraph 0288). The claimed cut-off value level of CEL to MG-H1 though the number itself is not directly called out—11.53--- would naturally follow and be made obvious to one of ordinary skill by the teachings above, since this would be the cut off level for both the compounds (CEL and MG-H1) in association with the claimed diseases (neurodegenerative alzheimers ) and since both of these things are taught by the prior art to diagnose alzheimers as is done in the art, the same above of below this cut off would indicate disease.
With respect to Claim 43, HANSSEN teaches of a method of measuring advanced glycation products/AGEs (title) in which the AGEs are known to be related to neurodegenerative diseases/disorders like Alzheimer’s (Page 172, paragraphs 1 & 2). GRUBER also teach of the claimed compounds being related to alzheimers disease (paragraph 0032-0033).
With respect to Claim 44, see Claim 28 rejection. HANSSEN teaches of the above and further teaches of a method of measuring advanced glycation products/AGEs (title) in which the AGEs are known to be related to neurodegenerative diseases/disorders like Alzheimer’s (Page 172, paragraphs 1 & 2). HANSSEN also teaches of determination of the amount/accumulation of these AGE compounds (which include MG-H1 and CEL) (Page 10, paragraph 1, line 8) and of detecting the accumulation of them through fluorescence and autofluorescence (Page 14, paragraph 1). HANSSEN further teaches of measuring the AGEs in comparison to healthy controls/a threshold wherein an increase compared to control indicates disease--- and measuring the two compounds together also show the claimed composite biomarker (paragraph 54, last paragraph, last two lines & Page 53, Figure 2B.5 & Page 53). The claimed cut-off values would follow naturally if a neurodegenerative disease is present, as this is how diagnostic science works.
HANSSEN does not teach specifically of treatment for alzheimers.
GRUBER teach of the claimed compounds being related to alzheimers disease (paragraph 0032-0033) of a treating the alzheimers disease (paragraph 0060).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to treat for alzheimers as is done in GRUBER in the methods of HANSSEN and TRELLU due to the advantages of administration of senescent cell removal agent has demonstrated as being effective for the treatment of Alzheimers (paragraph 0060).
Further- the claimed calculation of the claimed cut-off values from the spectrophotometric detection and optical density values would follow naturally if a neurodegenerative disease is present and as this is how diagnostic science works.
With respect to Claim 45, HANSSEN also teaches of determination of the amount/accumulation of these AGE compounds (which include MG-H1 and CEL) (Page 10, paragraph 1, line 8) and of detecting the accumulation of them through fluorescence and autofluorescence (Page 14, paragraph 1). HANSSEN further teaches of measuring the AGEs in comparison to healthy controls/a threshold wherein an increase compared to control indicates disease--- and measuring the two compounds together also show the claimed composite biomarker (paragraph 54, last paragraph, last two lines & Page 53, Figure 2B.5 & Page 53). The claimed cut-off values would follow naturally if a neurodegenerative disease is present, as this is how diagnostic science works.
Response to Arguments
Applicant’s arguments with respect to claim(s) have been considered but are moot because the new ground of rejection does not rely on the combination of references applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
The claims have been significantly amended dated 04/13/2026, necessitating new analysis of the claims and adjustment of the instant rejections. Therefore- the amendments and applicant’s arguments with respect to them are addressed by the rejections shown above.
The examiner thanks applicant’s representative for the interview dated 03/30/2026 and found it very helpful, though as the examiner is only given limited time for interviews, further issues were found with the amended claims that were not present before, notably the 112 issues shown above.
With respect to the 101 and prior art rejections, It is noted that the claims have been significantly amended and much detail was added to the claims. Therefore, these claims are addressed by the rejections shown above. Unfortunately, none of the added subject matter at the level of generality claimed reads on more than what is well understood, routine and conventional (these are things such as measuring optical density and binding anti-antibodies to plate surfaces and making detections therefrom, again especially at the level of generality these detections and the processing of the samples are claimed). Also- there is nothing claimed after the judicial exception is found, so not practical application. It is suggested that applicant review the USPTO subject matter eligibility example 29 to see what made some claims in that example allowable over others. The examiner notes that the prior art used in the instant rejection is the best which is found.
The 101 rejection is maintained, and further explained for the significantly amended claims as shown in the above rejection.
The prior art rejection, uses a new grounds of rejection including a new reference for the significantly amended claims.
With respect to the prior art, applicant argues that none of the prior art teaches of measuring the claimed composite biomarker. With respect to this, the examiner notes that this term is only used in the preamble of Claim 28. Within the claim body of Claim 28, in fact it seems like CEL and MG-H1 are measured and detected separately by different antibodies and that the “composite,” part is just a mathematical ratio/calculation performed on the individually detected CEL and MG-H1. The examiner maintains that the prior art and specifically HANSSEN does in fact teach of the CEL and MG-H1 individual detection as shown in the 103 rejection above and that these teachings read on this instant claims.
Applicant argues with respect to the Trellu reference that it does not teach of forming the claimed ratio of CEL to MG-H1. With respect to this, again the examiner maintains that HANSSEN make this obvious as it teaches detection of these two compounds together, and any formation of a ratio of them with respect to one another is just math.
In response to 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).
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, and maintains there is reason for combination as shown in the art rejection above.
In response to applicant's argument that the pieces of prior art are directed towards different things and are nonanalogous art, it has been held that a prior art reference must either be in the field of the inventor’s endeavor or, if not, then be reasonably pertinent to the particular problem with which the inventor was concerned, in order to be relied upon as a basis for rejection of the claimed invention. See In re Oetiker, 977 F.2d 1443, 24 USPQ2d 1443 (Fed. Cir. 1992). In this case, though the examiner sees that the focus of some of the pieces of prior art are different from what is instantly claimed, the examiner maintains that all of the prior art is still reasonably pertinent to the problem at hand.
Applicant also argues that the HANSSEN reference teaches away from ELISA type assays /antibody detection as claimed. The examiner disagrees. Though yes, the examiner sees that they say UPLC-MS is preferred, HANSSEN still teaches that ELISA assays can be used instead (Page 46).
All claims currently remain rejected.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
LOPES in US 20110124119
LOPES teaches of methods of measuring advanced glycation related products (abstract, paragraph 0008), of detecting Alzheimer’s disease (paragraph 0055), of detecting carboxyethyllysine (paragraph 0076), and performing ROC analysis (paragraph 0151, Table 3) using threshold values for comparison. The claimed cut-off values would follow naturally if a neurodegenerative disease is present, as this is how diagnostic science works. It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to perform ROC analysis and comparisons as is done in LOPES in the methods of HANSSEN, TRELLU, and GRUBER due to the advantage it offers for to comparison of the discriminatory power of various multivariate models (LOPES, paragraph 0151).
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/REBECCA M FRITCHMAN/Primary Examiner, Art Unit 1758
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