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 Final Office Action based on application 17/599316 RCE response filed 12/01/2025.
Claims 1-9, 16-20, & 22-24 have been examined and fully considered.
Claims 10-15 and 21 are cancelled.
Claims 23-24 are newly added.
Allowable Subject Matter
Claim 24 is allowed.
Reasons for Allowance
The following is an examiner’s statement of reasons for allowance:
For Claim 24, the prior art fails to disclose or reasonably suggest a method which requires treating as instantly claimed when the three gene expression product levels of CHGA, MASP1, and PLG are determined and compared to a reference sample, wherein a disease subtype is identified in a patient who has already been diagnosed with progression neurodegenerative disease, and the progressive neurodegenerative is subtyped specifically based on measured levels of CHGA , MASP1, and PLG, and wherein the disease subtype is one of a hyperplastic subgroup, a neuroinflammation subgroup, or a BBB dysfunction subgroup, and finally, treating by administering a β-secretase inhibitor when the patient is subtyped in a hyperplastic subgroup, administering an immune-modulating agent when the patient is subtyped in a neuroinflammation subgroup, and administering an anti-tau and/or anti-beta amyloid antibody or a block copolymer and/or a corticosteroid when the patient is subtyped in the BBB dysfunction subgroup, wherein the immune-modulating agent is PD-1, PD-L1 and/or CTLA-4 targeting antibodies, and/or p38 MAPK inhibitors, wherein the block copolymer is poly(ethylene oxide) and/or poly(propylene oxide), wherein the corticosteroid is dexamethasone, methylprednisolone, prednisone, prednisolone, cortisol, cortisone, betamethasone, triamcinolone, fludrocortisone acetate and/or deoxycorticosterone acetate.
Claim 24 has overcome the prior issues with respect to 101 and 112a.
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.
The claimed invention of Claims 1-9, 16-20 & 22 are directed to non-statutory subject matter.
The invention of instant claims 1-9, 16-20 & 22 are drawn towards a method of treating a patient comprising administering a B-secretase inhibitor, an immune modulating agent, an anti-tau and or anti-beta amyloid antibody, a block copolymer and/or a corticosteroid to the patient suffering from a progressive neurodegenerative disease.
Through 101, inquiry analysis:
Is the claim directed to a statutory category of invention?
Yes, the claims depending on Claim 1 & 23 are drawn towards a statutory category method.
Does the claims involve a Judicial Exception?
Yes. The claims including and depending from independent Claim 1 involves the judicial exceptions of a natural correlation (the expression level of gene expression products with the type/state of neurodegenerative disease).
While the preamble of the claim is drawn towards treating, the claim body itself does not always require treating, and therefore, the claim is still drawn towards a judicial exception as though not explicitly claimed is still implicitly there without practically applying or being significantly more. If applicant fixes that the claim body is left open to no treatment occurring, then the 101 rejection can likely be overcome.
Analysis of other factors to determine if the claim qualifies as eligible and ismore than the natural correlation. Do the claims practically apply at Step 2A, 2? Are they significantly more at step 2B?
There are no features instantly claimed in independent Claim 1, nor the claims which depend therefrom which practically apply the natural correlation.
In addition to the natural correlation (which includes the steps of providing a sample from the individual that comprises gene expression products, determining the level of three gene expression products which comprise CHGA, MASP1, and PLG, and typing the sample), comparison of the sample to reference levels is claimed.
This is all done as a data pull for determination of the judicial exception. This is extra pre-solution activity (data gathering – see MPEP 2106.05(g)). There is no particular practical integration.
Further- as claim in Claim 1 step b) there is an administration step, however as claimed the treatment can be one of including an “immune-modulating agent,” and a “block copolymer”. These terms are not particular or specific and can read on almost anything. Therefore- there is not always a practical application required by the claims.
See MPEP 2106.04(d)(2)(a). “Consider a claim that recites the same abstract idea and “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.”
With respect to whether the claims are significantly more, comparison to reference/control sample is well understood routine and conventional in the art. So is providing a sample. Also, treatment with corticosteroids and immune-modulating agents is also WURC and as these treatments are used for many different disease types is not particular or specific. Therefore- the claims do not amount to significantly more than the claimed judicial exceptions.
See USPTO eligibility examples 43 & 29. Also see Vanda Memorandum.
Also, see MPEP 2106.05(d) which deals with what is considered “Well-Understood, Routine and Conventional,” for both laboratory techniques.
See MPEP 2106.04 (a) Abstract Ideas, 2106.04 (b) Laws of Nature, Natural Phenomena & Products of Nature
Nothing in any of the dependent claims change the matters above.
Claims 2 & 17 specify that the sample is a body fluid and CSF. This is part of the natural correlation.
Claims 3-5 & 18-20 specify what the gene expression products are--- and that they are natural biomarkers like protein and CHGA and how many of them are detected. These are all natural products and part of the claimed natural correlation.
Claims 6 & 7 specify that either antibody and or beads are used to aid in detection of the gene expression products. Use of beads and antibodies to aid in detection, especially as generally claimed are routine and conventional in the art and therefore do not move the natural correlation to be a practical application.
Claims 8 & 9 specify that either flow cytometric immunoassay or mass spectrometry are used to aid in detection of the gene expression products. Use of both these techniques, especially as generally claimed are routine and conventional in the art and therefore do not move the natural correlation to be a practical application.
Claims 16 specifies that the disease is Alzheimer’s disease. This is part of the claimed natural correlation.
Claim 22 specifies that the block copolymer used as a possible treatment in Claim 1 is a poly ethylene oxide or polypropylene oxide. These are considered particular treatments, however, as claimed does not change the issue with the claimed treatment in Claim 1, that it is left open to treatment with an unparticular and specific treatment with a corticosteroid or immune modulating agent. Therefore Claim 22 is also rejected under 101.
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.
Claim 1 and Claims 2-9, 16-20, & 22-23 which depend from Claim 1 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for certain types of “immune-modulating agents,” “corticosteroids,” and “block copolymers,”, does not reasonably provide enablement for the realm of what can be encompassed by these terms. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
This decision was made in taking into consideration all of the Wands factors including:
(A) The breadth of the claims: It is noted that these claim terms encompass a broader scope than what is actually described in the instant specification.
(B) The nature of the invention: The nature of this invention is such that any and everything treatment which could be encompassed by these terms would not work to actually treat the patient.
(C) The state of the prior art: There are so many treatments available in the art one would not be able to just guess treatments that fit within the overly broad ones claimed that would work.
(D) The level of one of ordinary skill: The level of ordinary skill in this art is high, though even given that is the case, one would not be able to just guess treatments that fit within the overly broad ones claimed that would work.
(E) The level of predictability in the art: There are so many treatments available in the art that the level of predictability of what might work and what wouldn’t is not high.
(F) The amount of direction provided by the inventor: The inventor does provide some amount of direction, but again does not provide enough direction to show how one would be able to effectively treat a patient use any and every possibility encompassed by these terms.
(G) The existence of working examples: The inventor does provide working examples, but again there is not direction enough that would support effective use of any and every treatment which could be encompassed by these terms.
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure: There are so many treatments which could be encompassed by these terms, that the quantity of experimentation would be high and consequential for someone to determine if any and every treatment encompassed by these terms would work.
It is noted that “immune-modulating agents,” shown in instant PGPub paragraph 0107, the “corticosteroids,” in paragraph 0124, 0128, 0034 and “block copolymers,” in paragraph 0016 & 0127 are enabled. Applicant can note if there are other places where these terms are more fully enabled.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
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 1-9, 16-20, & 22-23 are rejected under 35 U.S.C. 103 as being obvious over RAY in US 20060094064 in view of WEINSTEIN in US 20120192298 and further in view of BACHA in US 20190091195.
With respect to Claim 1, 3, 5 & 23, RAY teaches a method of diagnosis or sub-classification/stratification, monitoring, and treating for Alzheimer's disease in a subject by detecting biomarkers(abstract). RAY teaches of measuring multiple biomarkers (paragraph 0120) where some of the biomarkers listed in the instant invention Table 2 are used and specifically teaching of detecting 3 biomarkers (paragraph 0120, 0124, claims 3 and 23). RAY further teaches that the biomarkers can be gene expression products (paragraph 0011, 0052, 0163), and can include MASP-1(listed on instant invention table 2) (paragraph 0229), GFP, EGF, PARC, ICAM, FAS, FGF, NAP (paragraph 0014), APOD (paragraph 0230) (which are shown in instant invention table 2), and of comparing a determined/measured level of the gene product biomarker to reference level (paragraph 0014, 0145). RAY further teach of pinpointing the type of dementia/stratifying the patient into different AD classes (paragraph 0010, 0018, 0022). RAY teaches of stratifying/sorting individuals into strata classes based on features of the neurological disease (paragraph 0054, 0123).
RAY does not teach of detecting CHGA or PLG as a biomarker.
WEINSTEIN is used to remedy this. WEINSTEIN more specifically teach of detection of Alzheimer’s by detecting genetic products (Table 2, paragraph 0139, 0166-0172) and of detecting neurodegenerative conditions by detecting CHGA and PLG (paragraph 0249) (which are both shown on instant application, Table II).
WEINSTEIN teach that the disease can be secretase related- and neoplasia (so overproduction) so individuals could be typed into a group where secretase inhibitor would need administered (this would read on applicant’s instant hyperplastic group) (See Table 1, paragraph 0139, 0193-0195), and further of treating the patient (assigning a treatment) (paragraph 0172).
It would have been obvious to one of ordinary skill in the art to use the biomarkers of WEINSTEIN to detect Alzheimer’s in the method of RAY due to the advantage the instant methods have been shown to have for diagnostic assaying (WEINSTEIN, paragraph 0165, 0171-0172).
RAY and WEINSTEIN teach of the claimed invention as shown in the above rejection. They also do not teach of the claimed treatment options of the using of using an immune modulating agent to address neuroinflammation, using an and anti-amyloid antibody to address BBB dysfunction, or using a block copolymer to address BBB dysfunction.
BACHA is used to remedy this and specifically teach of methods of detection and treatment of neurological conditions/deficits (paragraph 0013, 0021) and that the treatments are for improving neurological function. BACHA further teach of using immune stimulants and anti-inflammatories to treat the conditions (paragraph 0240, 0650, 0850). BACHA further teach of using anti-amyloid treatments/compounds (paragraph 0640) as part of a drug combination (paragraph 0500) and of treating due to blood brain barrier dysfunction (paragraph 0034). BACHA further teach of using copolymers are part of the treatments/compounds (paragraph 0898) and block copolymers (paragraph 0913, 0920) as part of a drug combination (paragraph 0500) and of treating due to blood brain barrier dysfunction (paragraph 0034). This can read on the claimed assigning through broadest reasonable interpretation as assigning is a mental process. This can read on the claimed assigning through broadest reasonable interpretation as assigning is a mental process. It would have been obvious to one of ordinary skill in the art to use/assign treatments as is done in BACHA in the method of RAY and WEINSTEIN due to the need in the art for better treatments for life-threatening diseases and due to the need in the art for treatments which can cross the blood brain barrier and due to the advantages treatment like curcumin have as being anti-inflammatory and anti-amyloid (plaque build ups) (BACHA, paragraphs 0003-0004), and due to the advantages treatment including block copolymers in the therapeutic has for incorporation into a nanoparticle for drug delivery (BACHA, paragraph 0913).
With respect to Claim 2, RAY teach of using a biological fluid sample (paragraph 0057).
With respect to Claim 4, RAY teach of the biomarkers/gene expression products being proteins (paragraph 0014, 0011, 0019, 0025, 0036).
With respect to Claim 6, RAY teach of the biomarkers/gene products being determined by antibody binding (paragraph 0140).
With respect to Claim 7, RAY teach of the biomarkers/gene products being determined by antibody/bead binding (paragraph 0140).
With respect to Claim 8, RAY and WEINSTEIN teach of the claimed invention as shown in the above rejection. They do not teach of the use of flow cytometry.
BACHA is used to remedy this and specifically teach of methods of detection and treatment of glioblastomas(abstract) and other neurological conditions/deficits (paragraph 0013, 0021). BACHA further teach of analyzing cell lines by using flow cytometry (paragraph 1562). It would have been obvious to one of ordinary skill in the art to use flow cytometry for analysis as is done in BACHA in the methods of RAY and WEINSTEIN due to the advantages it offers in analyzing full cell DNA content (BACHA, paragraph 1562).
With respect to Claim 9, RAY teach of using spectroscopy related technologies for detection such as MALDI-TOF and matrix assisted and ionization time of flight to measure the biomarkers (paragraph 0128). WEINSTEIN also teach of using mass spectrometry (paragraph 0204).
With respect to Claim 16, RAY teach of the neurodegenerative disease being Alzheimer’s disease (abstract, paragraph 0056).
With respect to Claim 17, RAY teach of using a biological fluid sample which is cerebrospinal fluid/CSF (paragraph 0057).
With respect to Claim 18, RAY teach of detecting at least 20 biomarkers (Tables 2A & B and also those in Table 3 and those in Table 7- which is over 200 biomarkers). RAY further teaches that the biomarkers can be gene expression products (paragraph 0011, 0052, 0163), and can include MASP-1(listed on instant invention table 2) (paragraph 0229), GFP, EGF, PARC, ICAM, FAS, FGF, NAP (paragraph 0014), APOD (paragraph 0230) (which are shown in instant invention table 2). RAY also teaches of screening and of a second screening making it obvious to screen for all present biomarkers (which can read on the checking for all biomarkers in AD disease) (paragraph 0088-0089). RAY does not teach of the exact biomarker variants as claimed in Table II of instant specification for some of the biomarkers.
WEINSTEIN is used to remedy this. WEINSTEIN more specifically teach of detection of Alzheimer’s by detecting genetic products (Table 2, paragraph 0139, 0166-0172) and of detecting neurodegenerative conditions by detecting CHGA (paragraph 0206, 0258), and PLG (Table II) (which are both shown on instant application, Table II). WEINSTEIN further teach of obtaining gene expression profiles which reads on determining the levels of gene expression products for a large number of genes (paragraph 0204-0206). See reason for combination in Claim 1.
With respect to Claim 19, RAY teach of detecting at least 20 biomarkers (Tables 2A & B and also those in Table 3 and those in Table 7- which is over 200 biomarkers). RAY further teaches that the biomarkers can be gene expression products (paragraph 0011, 0052, 0163), and can include MASP-1(listed on instant invention table 2) (paragraph 0229), GFP, EGF, PARC, ICAM, FAS, FGF, NAP (paragraph 0014), APOD (paragraph 0230) (which are shown in instant invention table 2). RAY also teaches of screening and of a second screening (which can read on the checking for all biomarkers in AD disease) (paragraph 0088-0089) making it obvious to screen for all present biomarkers. RAY does not teach of the exact biomarker variants as claimed in Table II of instant specification for some of the biomarkers.
WEINSTEIN is used to remedy this. WEINSTEIN more specifically teach of detection of Alzheimer’s by detecting genetic products (Table 2, paragraph 0139, 0166-0172) and of detecting neurodegenerative conditions by detecting CHGA (paragraph 0206, 0258), and PLG (Table II) (which are both shown on instant application, Table II). WEINSTEIN further teach of obtaining gene expression profiles which reads on determining the levels of gene expression products for a large number of genes (paragraph 0204-0206). See reason for combination in Claim 1.
With respect to Claim 20, RAY teach of detecting at least 20 biomarkers (Tables 2A & B and also those in Table 3 and those in Table 7- which is over 200 biomarkers). RAY further teaches that the biomarkers can be gene expression products (paragraph 0011, 0052, 0163), and can include MASP-1(listed on instant invention table 2) (paragraph 0229), GFP, EGF, PARC, ICAM, FAS, FGF, NAP (paragraph 0014), APOD (paragraph 0230) (which are shown in instant invention table 2). RAY also teaches of screening and of a second screening (which can read on the checking for all biomarkers in AD disease) (paragraph 0088-0089) making it obvious to screen for all present biomarkers. RAY does not teach of the exact biomarker variants as claimed in Table II of instant specification for some of the biomarkers.
WEINSTEIN is used to remedy this. WEINSTEIN more specifically teach of detection of Alzheimer’s by detecting genetic products (Table 2, paragraph 0139, 0166-0172) and of detecting neurodegenerative conditions by detecting CHGA (paragraph 0206, 0258), and PLG (Table II) (which are both shown on instant application, Table II). WEINSTEIN further teach of obtaining gene expression profiles which reads on determining the levels of gene expression products for a large number of genes (paragraph 0204-0206). See reason for combination in Claim 1.
With respect to Claim 22, BACHA teaches of the block copolymer being a polymer ethylene oxide and propylene oxide—since a polymer is made it would be “poly” ethylene oxide and propylene oxide as is also taught (paragraph 0913, 1524).
Response to Arguments
Claim 24 has been indicated as allowable a shown above.
Applicant's arguments filed 12/01/2025 with respect to the other claims have been fully considered but they are not persuasive.
If applicant’s representative files either a cancellation of the pending rejected claims or arguments after-final, the examiner will be willing to consider them.
Th 101 rejection for independent Claim 1 and the claims which depend therefrom is maintained for the reasons shown and further explained above. This is mostly because the claim only requires 1 treatment to meet the claim limitations, and some of the claimed treatments are not particular and specific.
There is no 101 rejection made for independent Claim 23, however a 112 a rejection is made. The 112 a rejection is also maintained for Claim 1. For Claim 23, this is due to the inclusion of “corticosteroids,” which the examiner thinks encompasses a much broader scope, than what is disclosed. For Claim 1, this is also due to the inclusion of “immune-modulating agents,” and “block copolymers,” which encompass a much much broader scope than what is claimed. For example, an immune modulating agent could be an NSAID or Tylenol, or something like an environmental toxin could be considered to be an immune modulating agent, and this is not disclosed instantly. For block copolymers, any macromolecule which covalently links to polymer chains could be this and applicant definitely does not have disclosure for this, nor would it be convincing that any block co-polymer would work as a treatment. It is possible, applicant could provide convincing arguments for Claim 23 to this affect with respect to corticosteroids, but the examiner is unsure if they would be convincing before considering. For Claim 1, it is unlikely that applicant could provide arguments to overcome the 112 rejection as claimed.
With respect to the prior art, applicant argues that “RAY does not teach of detecting CHGA or PLG,” and that “RAY nor WEINSTEIN teach of “the claimed treatment options of …using an immune modulating agent to address neuroinflammation, using an anti-amyloid antibody to address BBB dysfunction, or using a block copolymer to address BBB dysfunction.”
With respect to these arguments, the examiner points out that this is exactly why a 103 rejection was made. BACHA teaches of this as shown in the above rejection.
In response to applicant's arguments against the references individually, one cannot show non-obviousness 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).
Applicant also argues that the claims have been amended to indicate that a treatment is always required. The examiner agrees with this statement, however notes that BACHA teaches of treatment as claimed and that only one treatment is required to read on the claim limitations.
The examiner notes with respect to new claims 23 & 24, that claim 24 has been allowed and Claim 23 is rejected as shown above under 112 a and 103.
All claims remain rejected. The examiner would be happy to discuss after response if applicant’s representatives thinks this would help expedite prosecution for the claims which remain rejected.
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.
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