DETAILED ACTION
Status of Claims
Claims 8-19 and 21-23 are pending. Claims 1, 15, 18, and 20 have been amended. Applicant elected biomarkers CLU, C1R, ApoD, CFH, ApoF, CD14, APCS, FCN2, IGHG3, C8G, and CLEC3B in the reply filed on 04/28/2025.
Claims 8-19 and 21-23 are under examination.
Withdrawn Claim Objections and/or Rejections
The rejection of claims 15 and 18 under 35 USC 112(a) for failing to comply with written description as set forth on pp. 3-6 of the previous office action (mailed on 11/18/2025) has been withdrawn in view of the amended claims (filed on 11/18/2025).
The rejection of claims 8-19 and 21-23 under 35 USC 101 as being directed toward a judicial exception as set forth on pp. 8-11 of the previous office action (mailed on 11/18/2025) has been withdrawn in view of the amended claims (filed on 11/18/2025).
The rejection of claims 8-10, 19, and 20-24 under 35 USC 103 as being unpatentable over Butovsky and Van Meter et al., as set forth on pp. 12-24 of the previous office action (mailed on 11/18/2025) has been withdrawn in view of the amended and cancelled claims (filed on 11/18/2025).
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 8-19 and 21-23 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 enables one skilled in the
art to make and use the claimed invention in its full scope without resorting to 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 or complexity 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. See
In re Wands, 8 USPQ2d. 1400 (Fed. Cir. 1988).
In the instant case, the nature of the invention is complex and unpredictable, involving all
the possible combinations of the 35 proteins listed. As was found in Ex parte Hitzeman, 9
USPQ2d 1821 (BPAI 1987), a single embodiment may provide broad enablement in cases
involving predictable factors such as mechanical or electrical elements, but more will be
required in cases that involve unpredictable factors such as most chemical reactions and
physiological activity. This 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). See also In re Fisher, 427 F.2d 833, 839, 166 USPQ
18, 24 (CCPA 1970); Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 927 F.2d 1200, 1212, 18
USPQ2d 1016, 1026 (Fed. Cir.), cert. denied, 502 U.S. 856 (1991).
Claims 8-19 and 21-23 recite a list of 27 proteins and a combination of at least 2 proteins. Therefore, the claim recites a very large number of possible combinations of these proteins. The claim does not enable one to make and use the claimed invention for all the possible combinations. While the specification gives few examples for combinations, such as SEPP1 and SERPINA5 (see [0018]), it does not enable all of the possible combinations. For example, the specification lacks enablement for the combination of APOL1 and CD14. There is a lack of direction in Applicant's specification, even given knowledge in the prior art, as to whether administering treatment should be done based on the quantitation step for this combination, and similarly for each of the possible combinations recited. For example, there is no indication as to what change or how much of a change in concentration of each protein in the possible combination of proteins is required for the treatment to be administered. The specification offers insufficient guidance. Given the numerous combinations possible in claim 8, all the combinations do not appear to be enabled. The diagnostic art is highly unpredictable, and it would require undue experimentation for the full scope of the invention.
The remaining claims depend from claim 8 and still have the same issues.
Claim Rejections - 35 USC § 112-Response to Arguments
The arguments filed on 11/18/2025 have been considered by the examiner.
On p. 7 applicant argues that examples 3-11 teaches the claimed biomarkers being measured together. Example 3 teaches only measuring SERPINA5, but does not teach any amount of other protein with SERPINA5 or correlating that with any success in treatment with a multitude of possible treatments all working on different biochemical pathways. Further, example 3 does not teach the control value that the samples are being measured against. Example 3 does not provide any values and refers to an unknown control. Example 4 teaches only measuring APOA4, but does not teach any amount of other protein with APOA4 or correlating that with any success in treatment with a multitude of possible treatments all working on different biochemical pathways. Further, example 4 does not provide any guidance on the measurements of APOA4, it is unclear if the levels of APOA4 are increased or decreased and what the control is. Example 5 teaches only measuring APOF, but does not teach any amount of other protein with APOF or correlating that with any success in treatment with a multitude of possible treatments all working on different biochemical pathways. Further, example 5 does not teach the control value that the samples are being measured against. Example 5 does not provide any values and refers to an unknown control. Example 6 teaches only measuring CLU, but does not teach any amount of any other protein with CLU or correlating that with any success in treatment with a multitude of possible treatments all working on different biochemical pathways. Further, example 6 does not teach the control value that the samples are being measured against. Example 6 does not provide any values and refers to an unknown control. Example 7 teaches only measuring C1R, but does not teach any amount of other protein with C1R or correlating that with any success in treatment with a multitude of possible treatments all working on different biochemical pathways. Further, example 7 does not provide any guidance on the measurements of C1R. Example 7 does not teach what the control value is, thus it is unknown what C1R is decreased compared to. Example 8 teaches only measuring PROS1, but does not teach any amount of other protein with PROS1 or correlating that with any success in treatment with a multitude of possible treatments all working on different biochemical pathways. Further, example 8 teach the control value that the samples are being measured against. Example 8 does not provide any values and refers to an unknown control. Example 9 teaches only measuring SERPINF2, but does not teach any amount of other protein with SERPINF2 or correlating that with any success in treatment with a multitude of possible treatments all working on different biochemical pathways. Example 9 simply mentions that SERPINF2, SERPINA5, and SERPINA4 may be studied together in patients, but does not teach explicitly measuring SERPINF, SERPINA5, and SERPINA4 in one. Example 9 does not provide guidance on the measurement of SEPINF2, it does not teach the control values that the sample is being measured against. Further, example 9 simply just states that SERPINF2, SERPINA5, and SERPINA4 can be measured together, but does not provide any guidance on the measurements of those biomarkers. Example 9 does not teach if the measurements of SERPINF2, SERPINA5, and SERPINA4 should be increased or decreased and compared to what control value. Example 9 does not even teach the use of a control for SERPINF2, SERPINA5, and SERPINA4. Example 9 simply lists the biomarkers and states that they can be measured in a patient and does not correlate that with any success in treatment with a multitude of possible treatments all working on different biochemical pathways. Example 10 teaches that the following biomarkers are expressed at higher levels in those with motor neuron degeneration or ALS: APOA1, SERPINA5, SEPP1, CFH, CLU, and the following biomarker is expressed at lower levels in those with motor neuron degeneration or ALS: APOF, but does not teach measuring APOA1, SERPINA5, SEPP1, CFH, CLU, and APOF all together in one. Example 10 does not provide any guidance on what the control value is that the samples are being compared to. It is unknown what the samples are increased and/or decreased compared to. Example 10 does not correlate these markers with any success in treatment with a multitude of possible treatments all working on different biochemical pathways. Example 11 teaches levels of SERPINA5, APCS, CFH, IGFBP3, GP1Ba, IGHG3, APOF and APOA1 in those with motor neuron degeneration or ALS, but does not teach measuring all of the biomarkers together in one. Example 11 teaches measuring each of the biomarkers separately. Further, example 11 does not provide any guidance on what the control value is that the samples are being compared to. It is unknown what the samples are increased and/or decreased compared to. Example 11 does not correlate these markers with any success in treatment with a multitude of possible treatments all working on different biochemical pathways. Example 9 is the only example that mentions the potential to measure two or more specific biomarkers (SERPINF2, SERPINA5, and SERPINA4) together. However, example 9 teaches measuring the markers separately. Example 9 does not teach measuring SERPINF with any other marker in a patient at the same time. The specification does not enable any possible combinations of the proteins listed in claim 8. For example, the specification lacks enablement for the combination of C1R and FCN2. The instant specification does not provide any guidance on the measurements of each biomarker, such as which biomarker is increased and/or decreased compared to a control. The instant application does not teach what control the biomarkers are being compared to.
Further, applicant elected CLU, C1R, ApoD, CFH, ApoF, CD14, APCS, FCN2, IGHG3, C8G, and CLEC3B in the reply filed on 04/28/2025. Applicant then cancelled the recitation of CLU, CFH, ApoF, CD14, APCS, IGHG3, and CLEC3B in the amendments filed on 11/18/2025. The specification lacks enablement for any combination containing C1R, ApoD, FCN2, and C8G. While the examples teach the use of each biomarker, it does not enable all the possible combinations of the biomarkers. The specification simply teaches measuring each marker individually. The instant application appears prophetic as it does not provide any support for the measurement of two or more of the biomarkers listed and does not provide the measurements (increased and/or decreased) and what control the sample is being compared to. Thus, the 112(a)-enablement rejection is maintained.
Conclusion
No claim is allowed.
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 MCKENZIE A DUNN whose telephone number is (571)270-0490. The examiner can normally be reached Monday-Tuesday 730 am -530pm, Wednesday-Friday 730 am-430 pm.
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/MCKENZIE A DUNN/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678