DETAILED ACTION
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 .
Status of Application, Amendments and/or Claims
1. Claims 1-4 have been canceled and new claims 5-19 have been added as requested in the preliminary amendment filed October 15, 2021. Following the amendment, claims 5-19 are pending in the present application.
2. Applicant’s election of Group I, encompassing claims 5-6, in the reply filed on June 23, 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 7-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on June 23, 2026.
3. Claims 5-6 are allowable. Claims 7-19, previously withdrawn from consideration as a result of a restriction requirement, comprise all the limitations of an allowable claim. Therefore, pursuant to the procedures set forth in MPEP § 821.04(a), the restriction requirement among inventions I-III, as set forth in the Office action mailed on April 23, 2026, is hereby withdrawn and claims 7-19 are hereby rejoined and fully examined for patentability under 37 CFR 1.104. In view of the withdrawal of the restriction requirement, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
4. Accordingly, claims 5-19 are under examination in the current office action.
Information Disclosure Statement
5. The information disclosure statement (IDS) filed 05/13/2022 has been reviewed and the references therein are of record.
Drawings
6. The drawings are objected to because the contain color drawings. See in particular Figures 14 and 15, wherein the specification describes the different bars in the graph as having different colors. Additionally, Figures 16-23, 26-38 and 42-44 all contain lines or bar graphs with various shades of gray that are difficult to distinguish from each other. The figures appear to have been created in color, and then printed in grayscale. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
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.
7. Claims 10-19 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 a method of detecting a biomarker (or a change in the level/amount of a biomarker) associated with Parkinson’s disease (PD) in a subject comprising contacting a sample obtained from the subject with the DARPin encoded by SEQ ID NO: 22, does not reasonably provide enablement for a method of detecting a biomarker (or a change in a biomarker) of traumatic brain injury (TBI), neuronal damage or susceptibility to any neurodegenerative disease as broadly claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
The factors to be considered in determining whether a disclosure would require undue experimentation 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. In re Wands, 8 USPQ2d, 1400 (CAFC 1988).
Claim 10 and dependent claims thereof are drawn to a method of detecting a biomarker of TBI, neuronal damage, and/or susceptibility to neurodegenerative disease in a subject, which comprises contacting a sample from the subject with the designed ankyrin repeat protein (DARPin) of claim 5 (the DARPin encoded by SEQ ID NO: 22) and detecting whether the DARPin binds to the sample. Claim 12 and dependent claims thereof are directed to a method of detecting a change in a biomarker of TBI, neuronal damage, and/or susceptibility to Parkinson’s disease (PD) in an injured subject, comprising contacting samples obtained from a subject two or more times post-injury with the DARPin of claim 5 (the DARPin encoded by SEQ ID NO: 22); and comparing the level of the DARPin bound to the samples. Note that the term neuronal damage can broadly encompass any insult to the central or peripheral nervous system, including not only physical injury but also insult due to infectious agents or parasitic organisms, toxic or pharmacologic agents, ischemic or hemorrhagic stroke, inflammation, or even neuropsychiatric disorders, among other insults. And the breadth of a subject susceptible to neurodegenerative disease (ND) would include any person who lives long enough to develop an ND, because advanced age is the primary risk factor for developing a ND. Accordingly, the claims are broadly drawn to the detection of a biomarker, or change in a biomarker, of TBI, any non-specific neuronal damage or susceptibility to any neurodegenerative disorder in any subject, by detecting the binding of the DARPin encoded by SEQ ID NO: 22 to a subject’s sample.
In contrast to the breadth of the claimed invention, what is provided in the instant application is quite narrow. While a DARPin was discovered through a process of biopanning (both negative panning (NP) and positive panning (PP)) of a N1C phage library to isolate DARPin proteins that specifically recognized different neurodegenerative-associated biomarker proteins, and a DARPin that displayed reactivity to neural tissue from a PD patient specifically (see Example 3 at pp. 59-60), it is unclear whether that DARPin is the protein encoded by the instant SEQ ID NO: 22. For the purpose of examination, it will be assumed that the DARPin encoded by SEQ ID NO: 22 of the instant claims is the PD-reactive DARPin isolated in Example 3 of the specification.
Given that the art recognizes Parkinson’s disease as a chronic, neurodegenerative disease accompanied by numerous biochemical and structural changes within central nervous system of a patient, one of ordinary skill in the art would hypothesize that the PD-specific DARPin discovered by applicant is reactive to some unique biomarker (likely, though not verified, phosphorylated alpha-synuclein; see, for instance, Baba et al. Am J Path. 1998, 152(4):879-884; listed on IDS) that occurs exclusively within PD patients. The instant specification teaches, for instance, that the PD-specific DARPin was isolated based upon negative panning (NP) against samples from healthy subjects and Alzheimer’s disease (AD) patients in addition to positive panning (PP) for samples from PD patients (see Fig. 3). However, there is no indication that this PD-specific DARPin would also be capable of binding to a biomarker associated with TBI, another form of neural injury, or a different neurodegenerative disease altogether, or else would be capable of detecting such a biomarker within 6 hours post-injury, within 12-36 hours post-injury, within 5-10 days post injury, or within 2-4 weeks (days?) post-injury according to the presently claimed invention.
The prior art recognizes that designed ankyrin repeat proteins (DARPins) are binding molecules that bind with high affinity to a desired target, and combinatorial libraries of these designed AR proteins can thus be utilized to enrich for target-specific binders as an alternative to antibody libraries (see Binz et al. (2004) Nat Biotech. 22(5):575-582). The specification also provides examples of single chain antibody variable domain fragments (svFv or nanobodies) that are capable of specifically binding and detecting key biomarker proteins associated with various neurodegenerative diseases or with traumatic brain injury (TBI) (see Examples 4 and 5), but these molecules are wholly distinct from the DARPin molecule of the instant claims. Therefore, the instant application does not provide adequate guidance to support the breadth of the presently claimed invention. Undue experimentation would thus be required of the skilled artisan to determine if the DARPin encoded by SEQ ID NO: 22 could indeed not only detect a biomarker associated with TBI or neural injury as broadly claimed, but also could detect changes in biomarker levels in as few as 6 hours post-injury and potentially up to 4 weeks post-injury.
The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue. In view of the breadth of the claims, the lack of guidance and working examples provided in the specification, the high level of unpredictability as evidenced by the prior art, and the amount of required experimentation, it is the examiner’s position that undue experimentation would be necessary for a skilled artisan to make and use the entire scope of the claimed invention. Applicants have not provided sufficient guidance to enable one of ordinary skill in the art to practice the claimed invention in a manner reasonably correlated with the scope of the claims. The scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without sufficient guidance, determination of having the desired biological characteristics is unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir., 1988).
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.
8. Claim 16 is 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.
Claim 16 is indefinite for reciting “about 2 to 4 weeks days” because it is unclear whether this means 2-4 weeks or 2-4 days. The metes and bounds of the claim therefore cannot be determined.
Conclusion
9. Claims 5-9 are allowed. Claims 10-19 are rejected. The prior art does not teach or relatively suggest the nucleic acid sequence of SEQ ID NO: 22, or a protein encoded thereby.
Advisory Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kimberly A. Ballard whose telephone number is (571)272-2150. The examiner can normally be reached Mon-Fri 8AM - 5PM EST.
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, Jeffrey Stucker can be reached at 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/KIMBERLY BALLARD/Primary Examiner, Art Unit 1675
Prosecution Insights