DETAILED CORRESPONDENCE
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 .
This action is in response to the papers filed November 11, 2025. Currently, claims 1, 5-12 and 16-20 are pending.
All arguments have been thoroughly reviewed but are deemed non-persuasive for the reasons which follow. This action is made FINAL.
Any objections and rejections not reiterated below are hereby withdrawn.
Priority
This application claims priority to provisional 63/268,574, filed February 25, 2022.
The provisional application filed February 25, 2022 is a one page poster. The disclosure in the provisional application does not support the instant claims.
The instant claims enjoy the benefit of February 24, 2023.
Drawings
The drawings filed November 11, 2025 are acceptable.
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 of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 5-12 and 16-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
35 U.S.C. § 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. M.P.E.P. § 2106. Regarding judicial exceptions, “[p]henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972); see also M.P.E.P. § 2106, part II.
Based upon consideration of the claims as a whole, as well as consideration of elements/steps recited in addition to the judicial exception, the present claims fail to meet the elements required for patent eligibility.
Question 1
The claimed invention is directed to a process that involves a natural principle and a judicial exception.
Question 2A Prong I
The claims are taken to be directed to an abstract idea, a law of nature and a natural phenomenon.
Claim 1 is directed to “a method of detecting an immune response to Alzheimer’s disease progression by translating the a CDR of a T cell receptor alpha and a TAU sequence into amino acid sequence, determining a chemical complementarity score and detecting progression of AD by comparing sample to a reference control. Claim 1 then provides low chemical complementarity indicated low Braak stage and high chemical complementarity indicates mid-level or advanced level compared to a control.
Claim 1 is directed to a process that involves the judicial exceptions of an abstract idea (i.e. the abstract steps of “detecting an immune response to AD progression in a subject”, translating nucleic acid sequences into amino acid sequences; determining a chemical complementarity score and comparing chemical complementarity from a subject and a control) and a law of nature/natural phenomenon (i.e. the natural correlation between chemical complementarity scores and Braak stage).
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons that follow.
Herein, claim 1 involves the patent-ineligible concept of an abstract process. Claim 1 requires performing the step of “translating” the first and second nucleic acid sequences into an amino acid sequence. This translation from nucleic acid sequence to amino acid sequence is a mental step that essentially compares the three nucleotides to a codon chart to provide the amino acid sequence. This translation may be performed in the mind.
The claim also requires “determining a chemical complementarity score”. The specification teaches chemical complementarity is a key feature of scoring protein-protein interactions. The specification teaches the chemical complementarity scoring process may be performed using a commercially available website (adaptivematch.com). This computer performs an algorithm, mathematical calculation (para 4 and 130). This limitation is a mathematical concept within the grouping of abstract ideas.
The claim further requires wherein a low complementarity score indicated low level Braak stage and high chemical complementarity indicates a mid-level or advanced level Braak stage of Alzheimer’s disease. As broadly recited the indication may be accomplished mentally by thinking about a subject’s complementarity score. Thus, the detecting step constitutes an abstract process idea.
Claim 1 further recites a comparison between the complementarity score in a sample from a subject and a control that is deemed an abstract idea (see MPEP 2106.04(a)(2)(III)(A); • claims to “comparing BRCA sequences and determining the existence of alterations,” where the claims cover any way of comparing BRCA sequences such that the comparison steps can practically be performed in the human mind, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 763, 113 USPQ2d 1241, 1246 (Fed. Cir. 2014)).
A correlation that preexists in the human is an unpatentable phenomenon. The association between chemical complementarity scores and Alzheimer’s disease progression or Braak stage is a law of nature/natural phenomenon. A step which tells users of the process to predict progression of Alzheimer’s disease in the sample, amounts to no more than an "instruction to apply the natural law" and is no more than a mental step. Even if the step requires something more such as to verbalize the discovery of the natural law, this mere verbalization is not an application of the law of nature to a new and useful end. The wherein clause does not require the process user to do anything in light of the correlation. The wherein clause fails to provide the “practical assurance” sought by the Prometheus Court that the “process is more than a drafting effort designed to monopolize the law of nature itself.”
Question 2A Prong II
The exception is not integrated into a practical application of the exception. The claims do not recite any additional elements that integrate the exception into a practical application of the exception. While the claim recites obtaining a sample and sequencing nucleic acids, this is not an integration of the exception into a practical application. Instead, these elements are data gathering required to perform the method. Thus, the claim is “directed to” the exception.
Claim 9 is directed to “administering a therapeutic composition after detecting the progression of Alzheimer’s disease”. The claim requires administering regardless of what the progression is. Thus, the claim requires administering the same therapeutic compositions to patients with high and low progression. The treatment is administered regardless of disease progression, thus, this is not an integration of the judicial exception. The claim does not specify which patients are treated or only treat a specific patient population based upon their genetic composition. Thus, the claim is directed to a judicial exception.
Claim 12 is directed to administering a therapeutic to slow the progression of Alzheimer’s disease in the subject. Like Claim 9, the treatment is provided regardless of the results determined. Further, the claim is generic to the therapeutic composition and is not a particular treatment.
Question 2B
The second step of Alice involves determining whether the remaining elements, either in isolation or combination with the other non patent ineligible elements, are sufficient to “’transform the nature of the claim’ into a patent eligible application” Alice, 134 S. Ct. at 2355 (quoting Mayo, 132 S. Ct. at 1297).
The claims are not sufficiently defined to provide a method which is significantly more from a statement of a natural principle for at least these reasons:
The claims do not include applying the judicial exception, or by use of, a particular machine. The claims do not tie the steps to a “particular machine" and therefore do not meet the machine or transformation test on these grounds. The use of machines generally does not impose a meaningful limit on claim scope.
The claims also do not add a specific limitation other than what is well-understood, routine and conventional in the field. The sequencing of nucleic acid sequence is mere data gathering step that amounts to extra solution activity to the judicial exception. It merely tells the users of the method to determine the sequencing of nucleic acid sequence without further specification as to how the sample should be analyzed. The claim does not recite a new, innovative method for such determination. The determining step essentially tells users to determine the markers through whatever known processes they wish to use.
The step of sequencing of nucleic acid sequence was well known in the art at the time the invention was made. The claim merely instructs a scientist to use any sequencing method to determine the sequence. The claim does not require the use of any particular non-conventional reagents. When recited at this high level of generality, there is no meaningful limitation that distinguishes this step from well understood, routine and conventional activities engaged in by scientists prior to applicant’s invention and at the time the application was filed.
Further it is noted that the courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity.
Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs., 818 F.3d at 1377; 118 USPQ2d at 1546;
Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014)
For these reasons the claims are rejected under section 101 as being directed to non-statutory subject matter.
Response to Arguments
The response traverses the rejection. The response asserts Claim 1 is not directed to the judicial exceptions because the claim amounts to significantly more.
This argument has been considered but is not convincing because the response does not point to any limitations that are significantly more and the claims do not require significantly more, as outlined in the rejection above. Thus for the reasons above and those already of record, the rejection is maintained.
Claim Rejections - 35 USC § 112-Description
The following is a quotation 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.
Claims 1, 5-12 and 16-20 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are broadly drawn to methods which comprise a first CDR of a T cell receptor alpha (TRA) and TAU protein that detect immune response to Alzheimer’s disease progression.
Relevant to the lack of particular structural limitations in the rejected claims drawn to nucleic acids, MPEP 2163 states:
The claimed invention as a whole may not be adequately described if the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional in the art or known to one of ordinary skill in the art.
In the case of the instant claims, the functionality of identifying comprise a first CDR of a T cell receptor alpha (TRA) and TAU protein that detect immune response to Alzheimer’s disease progression when used in a chemical complementarity score is a critical feature of the claimed methods.
The specification teaches a CDR or TRA and TAU sequence for chemical complementarity score analysis to predict progress of AD. The specification teaches TRA CDR3s and Tau (MAPT) protein may be used in complementarity score analysis to determining Braak stages (Tables 8-9). Given the guidance in the specification and what was taught in the art prior to the invention, the skilled artisan would be unable to predictably correlate progression of Alzheimer’s disease using any CDR and TAU.
The genus of misfolded or aggregated protein associated with AD is extremely large. The specification only teaches the Tau protein and segments 2-6. The art teaches amyloid beta, ACT, RCAn1-1L, VDAC1, PSEN1, PSEN2 mutations, for example that are associated with AD. There is no description which AD associated sequences may be used for the chemical complementarity analysis with which CDRs. The specification has described only one pair of sequences that may be used for chemical complementarity score analysis.
The art teaches CDR1 and CDR2 are found in the variable (V) region of a polypeptide chain, and CDR3 includes some of V, all of diversity (D, heavy chains only) and joining (J) regions. CDR3 is the most variable. The V region sequence undergoes rearrangement during B-cell development, somatic recombination. The rearrangement of the V-region is where the CDR-L3 and CDR-H3 are encoded and diversified, whereas the other four CDRs are generated in the germ-line. The specification is limited to CDR3.
The general knowledge and level of skill in the art do not supplement the omitted description because specific, not general guidance is what is needed. Since the disclosure fails to describe the common attributes or characteristics that identify members of the genus, and because the genus is highly variant, a CDR of TRA and TAU alone is insufficient to describe the genus. There is no description of which CDRs may be used in chemical complementarity score analysis.
Thus, considering the breadth of the polynucleotides required by the claimed methods, their specific required functionalities, and the teachings of the instant specification, it is the conclusion that the specification does not provide an adequate written description of the broadly claimed subject matter.
Response to Arguments
The response traverses the rejection. The response asserts Example 1 of the application discloses using nucleic acid sequence/amino acid sequence of CDR or a TRA and TAU protein to obtain a chemical complementarity score. This argument has been considered but is not convincing because the specification and Example 1 are limited to CDR3. The claims would also encompass CDR1 and CDR2 that are less variable than the CDR3 region. The specification does not describe which CDR may be used for the immune response analysis. The specification only teaches the CRD3 region is associated. Thus for the reasons above and those already of record, the rejection is maintained.
Claim Rejections - 35 USC § 112- Enablement
The following is a quotation 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.
Claims 1, 5-12 and 16-20 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (CA FC 1988). Wands states at page 1404,
“Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.”
The nature of the invention and breadth of claims
The claims are broadly drawn to methods which comprise sequencing a CDR of a T cell receptor alpha (TRA) and a TAU protein or fragment to be used in a chemical complementarity score analysis of determining immune response to Alzheimer’s disease progression.
The invention is in a class of invention which the CAFC has characterized as “the unpredictable arts such as chemistry and biology.” Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
The unpredictability of the art and the state of the prior art
The art teaches determining complementarity scores of antigen-binding proteins and proteins associated with cancers for diagnosing and treating cancers (Blanck et al. US 2024/0093296). Blanck illustrates a flow chart to how to obtain and select CDR and antigen-binding proteins (Figure 19). This generic outline for selecting CDR and second nucleic acid sequences does not enable the skilled artisan to select the sequences for AD analysis. Figure 20 illustrates different CDR and genes and demonstrates different complementarity scores for the different combinations (para 65). Thus not all combinations share the same results and are not interchangeable.
Guidance in the Specification.
The specification provides no evidence that the broad scope of any CDR and TAU could be used in a chemical complementarity score to detect progression of Alzheimer’s disease. The specification provides analysis of a single TRA CDR3 and Tau Segments 2-6 are associated with Alzheimer’s disease.
The guidance provided by the specification amounts to an invitation for the skilled artisan to try and follow the disclosed instructions to make and use the claimed invention.
Quantity of Experimentation
The quantity of experimentation in this area is extremely large since there is significant number of parameters which would have to be studied to enable the skilled artisan to use the claimed invention as broadly as claimed.
The claims are directed to detecting a progression of AD in a subject. Progression is the process of moving forward or developing gradually. The specification does not provide any analysis of progression over a time period. The specification provides analysis at a single time point of the Braak stage. This is not indicative of progression over time. It is unpredictable the chemical complementarity score provides any guidance to how progression may be detected. This would require further unpredictable and undue experimentation.
The claims are also directed to any CDR of TRA. The specification provides a single example of TRA CDR3 and Tau protein to determine chemical complementarity score and assess Braak stage of AD. It is unpredictable which CDR and which misfolded or aggregated proteins may be used to determine progression of AD without further unpredictable and undue experimentation.
This would require significant inventive effort, with each of the many intervening steps, upon effective reduction to practice, not providing any guarantee of success in the succeeding steps.
Level of Skill in the Art
The level of skill in the art is deemed to be high.
Conclusion
Thus given the broad claims in an art whose nature is identified as unpredictable, the unpredictability of that art, the large quantity of research required to define these unpredictable variables, the lack of guidance provided in the specification, the absence of a working example and the negative teachings in the prior art balanced only against the high skill level in the art, it is the position of the examiner that it would require undue experimentation for one of skill in the art to perform the method of the claim as broadly written.
Response to Arguments
The response traverses the rejection. The response asserts Example 1 of the application discloses using nucleic acid sequence/amino acid sequence of CDR or a TRA and TAU protein to obtain a chemical complementarity score. This argument has been considered but is not convincing because the specification and Example 1 are limited to CDR3. The claims would also encompass CDR1 and CDR2 that are less variable than the CDR3 region. It would be unpredictable for the skilled artisan to perform additional undue experimentation to determine whether all of the CDR of TRA may be used for detecting an immune response to Alzheimer’s disease progression. The specification only teaches the CRD3 region is associated. Thus, for the reasons above and those already of record, the rejection is maintained.
Claim Rejections - 35 USC § 112- Second Paragraph
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.
Claims 1, 5-12 and 16-20 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 pre-AIA the applicant regards as the invention.
Claim 1 has been amended to require a “low chemical complementarity score indicates…” and a “high chemical complementarity score indicates…”. High and Low are relative terms. The term “high” and “low” in claim 1 is a relative term which renders the claim indefinite. The term “high” and “low” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Conclusion
No claims allowable.
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 JEANINE ANNE GOLDBERG whose telephone number is (571)272-0743. The examiner can normally be reached Monday-Friday 6am-3:30pm.
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/JEANINE A GOLDBERG/Primary Examiner, Art Unit 1682
February 18, 2026