DETAILED ACTION
The present application is being examined under the pre-AIA first to invent provisions.
Applicant’s response and amendments received September 17, 2026 are acknowledged.
Claims 1-39, 49, and 50 have been canceled.
Claims 40, 51, 52, 56, and 58 have been amended.
Claims 40-48 and 51-59 are pending in the instant application.
Information Disclosure Statement
The IDS form received 9/17/2026 is acknowledged and the references cited therein have been considered.
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.
The rejection of claims 40-59 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite has been withdrawn in view of applicant’s claim amendments received September 17, 2026 which clarify when samples must be taken as well as the minimum number of samples needed to satisfy the claimed methods.
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 40-48 and 51-59 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.
Applicant has amended the claims as part of the September 17, 2026 response yet said claims still broadly recite methods for evaluating treatment hereditary angioedema, such a method comprising the steps of contacting a first biological sample obtained from a subject before treatment and a second biological sample obtained either after or during treatment, wherein the capture reagent is one or both of FXII and pKal that bind C1-INH, measuring the amount of C1-INH bound, and
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As was previously set forth in the prior office action, “step (iv) compels the method’s practitioner to administer a therapeutic agent to a subject identified as “not responsive” in step (iii) yet there is no indication in claim 40 (or indeed in any claim apart from dependent claims 51 and 52) that there is any difference between what is administered in part (i) as compared to what is administered in part (iv). It should be readily apparent that the subjects “identified” in part (iii) are labeled as being “non-responsive” and thus administering the same treatment in (iv) as in (i) is very reasonably expected to be an abject failure, yet this has not precluded applicant from claiming just such a method.”
Applicant does not agree with such logic, stating on page 7 of the 9/17/2026 response
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It should be noted that the passage above appears to be an admission by applicant on the record that the claimed method is not inherently accurate and must be performed multiple times (or at least more than once as is required by the claims) in order for the clinician to confirm if a subject actually is or is not “non-responsive”. Notably, all claims currently presented only require a single comparison to be made, i.e. 1 (before) to 2 (after or during). Thus applicant’s arguments indicate that multiple comparison steps must be made before a clinician would accept a finding of “non-responsiveness” and since only one comparison is required the instant claimed methods are not reasonably enabled as evidenced by applicant’s statement quoted above. Further, continuing to administer the same therapy to a subject when it is known that therapy does not work does not appear to be a reasonable course of action for someone who (presumably) has a duty of care regarding the subject since the subject’s disease is not being effectively treated in any way. Applicant is reminded that method claims are limited by what concrete, observable process steps they require the practitioner to take and apart from instant claims 51 and 52 there is no requirement that treatment be altered in any way when it is found to be ineffective. As set forth in the prior office action, it is not reasonable to continue treatment of a subject with a therapy that is known not to work as apart from the ability to confirm results from an inherently inaccurate assays as proffered by applicant it does not provide any benefit to the subject, and in fact is harmful to said subject as it minimally wastes their time.
Further, apart from issues surrounding how many distinct “therapeutic agents” are required by the claimed inventions as discussed above, the identity of such an agent(s) is/are also completely unspecified in the instant claimed inventions apart from dependent claim 53. Independent claim 40 reasonably indicates that “successful” therapeutic agents will increase measured C1-INH in the subject samples following administration, but as presently written apart from claim 53 there is no requirement that the administered agent actually have this effect or even be expected to have this effect and the therapeutic agent can be anything. While the specification discloses a reasonable mechanistic pathway regarding why the disparate reagents recited in claim 53 (apart from administering exogenous C1-INH which is self-explanatory) are in fact actually reasonably expected to boost C1-INH, such constraints are not binding upon the instant claimed invention other than with regard to dependent claim 53 itself, and identifying additional therapeutic agents that are to be used in the claimed methods does not seem possible in the absence of performing additional unpredictable basic science research and experimentation concerning such “therapeutic” agents.
Applicant disagrees, arguing
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First, it must be stated that the specification filed on 12/19/2023 in the instant file wrapper does not contain paragraph numbers. Given that the source of this numbering convention does not appear to be specified in applicant’s remarks received 9/17/2026 it is unclear what exactly applicant is arguing. Second, as applicant is well aware, limitations in the specification are not to be read into the claimed invention except in the case of definitions. In the present case, “therapeutic agent” is not a term that is defined by the 12/19/2023 specification (see specifically pages 12-22). While the specification does provide examples of “therapeutic agents”, such as those reagents which are presently recited in instant claim 53, the breadth of the claims (apart from 53 that is) are not limited thereto. Thus the claimed methods do encompass the administration of anything as a “therapeutic agent”, especially as applicant has taken considerable pains to argue why in applicant’s opinion a “therapeutic agent” does not actually have to work to treat the disease (i.e. continuing to administer a drug for which the patient is by applicant’s own assay “non-responsive” is perfectly fine in applicant’s opinion) certainly indicates that applicant intends the claims to encompass the administration of “therapeutic agents” far in excess of thing known in the art or indeed things even reasonably expected by artisans to have any chance of therapeutic utility in treated HAE.
Therefore, in view or the breadth of the claims, the guidance and direction of the working examples, and the teachings of the art, artisans would not reasonably be able to practice the full breadth of the instant claimed methods without first engaging in additional unpredictable trial and error basic science research and experimentation.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 40-59 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,892,450. Although the claims at issue are not identical, they are not patentably distinct from each other because the issued claims anticipate the breadth of what is presently claimed.
Specifically, issued independent claim 1 recites methods for treating pKal-mediated disorders defined as including hereditary angioedema, by (i) contacting a subject sample with a) an active form of Factor XII, or a C1-INH binding fragment thereof, b) an active form of pKal, or a C1-INH binding fragment thereof, or c) a combination of a) and b), (ii) measuring a level of the C1-INH in the sample that binds to the capture reagent, (iii) identifying the subject as having a pKal-mediated disorder if the measured C1-INH is lower than a normal control, and (iv) treating an identified subject with a therapeutic agent selected from a small Markush group. Notably, dependent claims recite that such a method is used to monitor therapeutic efficacy, with a rise in C1-INH indicating effective therapy (see most particularly issued claim 14), that the subject sample is blood or plasma (see particularly issued claim 5), and that ELISA and other assays can be used to measure C1-INH (see particularly issued claim 9). It should be obvious that the only way effectiveness over time can be measured is by obtaining samples at numerous timepoints. Practicing such methods on subjects who are resistant to anti-histamines and corticosteroids is explicitly claimed (see issued claim 15) as is practicing on subjects with no prior symptoms (issued claim 18). It should be apparent that the only way effectiveness over time can be measured is by obtaining samples at numerous timepoints even if such a limitation is not explicitly recited. Given that the issued claims are significantly more specific with regard to the administered therapeutic agent as compared to the instant claims, the issued claims necessarily anticipate that which is presently claimed. Further, applicant is reminded that the instant application is a continuation of the application giving rise to the ‘450 patent and thus 35 USC 121 is not relevant to the present situation.
Applicant's arguments filed September 17, 2026 have been fully considered but they are not persuasive. Applicant argues that “In contrast, claims 1-20 of U.S. Patent No. 11,892,450 do not disclose or suggest a method comprising identifying the subject as not responsive to the treatment (amended claim 1(iii)) and administering to a subject identified as not responsive to the treatment a therapeutic agent (amended claim 1(iv)), as recited in the pending claims.”
These arguments have been considered and are not persuasive. As discussed in the rejection of record, an artisan practices the instant recited process steps of contacting patient samples with the recited reagents both to identify a subject to be treated with a therapeutic agent (issued claim 1) and to monitor effectiveness over the course of treatment with the therapeutic agent (issued claim 14). While the issued methods do not explicitly call out the mental step of “identifying a subject as non-responsive” as discussed at length earlier in this action such an “identification” does not produce any observable change in the practitioner’s actions as such an “identification” does NOT require a change in administered argent, or even a change in dosing frequency or drug mass. Applicant is reminded that claims are limited by what they require an artisan to do, not what applicant might wish to read in or imply is done in a particular circumstance. Given that the instant recited measurements and comparisons are performed in the issued methods, and the fact that there is no required change in how the subject is treated following the mental decision that the subject is “non-responsive” there appears to be no way an observer could distinguish between someone practicing the instant claimed methods versus the previously issued methods as mentally deciding that someone is non-responsive doesn’t necessarily alter therapy in any way. Again, method claims are limited by the observable process steps they require the practitioner to perform, not what they imply someone could do or what reasonably is obvious for a practitioner to do if they actually cared about the subject and took their hypocritic oath seriously. The rejection is maintained.
No claims are 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 Michael Szperka whose telephone number is (571)272-2934. The examiner can normally be reached Monday-Friday 8:30-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached at 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Michael Szperka
Primary Examiner
Art Unit 1641
/MICHAEL SZPERKA/Primary Examiner, Art Unit 1641
