DETAILED ACTION
The present application is being examined under the pre-AIA first to invent provisions.
Applicant’s preliminary amendments received June 3, 2024 are acknowledged.
Claims 1-39 have been canceled,
Claims 40-59 have been added.
Claims 40-59 are pending in the instant application.
Information Disclosure Statement
The IDS form received 6/3/2024 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.
Claims 40-59 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
In part (i) of the claimed method, samples are recited as being obtained from a subject a) before treatment, b) after treatment, and/or c) during the course of treatment. Thus, due to the “and/or” the claim sets forth seven distinct embodiments, namely, a alone, b alone, c alone, a+b, a+c, b+c, and a+b+c. However, part (iii) of the claim requires comparing either a “b sample/after” or a “c sample/during” to an “a sample/before”. Thus the claim is logically inconsistent, as practicing step (iii) requires comparison to an “a/before” sample yet such a sample is not required to be obtained in part (i). An even greater logical inconsistency occurs in step (iv) which requires “administering to the subject identified in step (iii) a therapeutic agent for treating the pKal-mediated disorder.” Given that the subject must have necessarily been treated with a therapeutic reagent in order to obtain the necessary samples in part (i) to perform the analysis of part (iii), the administration of step (iv) is not logical as it must have already occurred given that retroactive administration/time travel is not possible. Applicant appears to be aware of this issue as evidenced by dependent claims 51 and 52. Claim 51 recites that the dose and/or frequency increase in part (iv) relative to (i) as the reagent is the same whereas claim 52 recites that the therapeutic agent of (iv) is a different therapeutic agent as the treatment of (i). Given that dependent claims are always necessarily narrowing as compared to the preceding claim (see 35 USC 112(d) in particular) the dependent claims serve as evidence that in claim 40 the agent of parts (i) and (iv) can be completely identical in all ways. It should also be readily apparent that if it is assumed that the subject at step (i) is already being treated with an agent, and analysis of such a treatment (as is performed in step (iii)) indicates it isn’t working, why continue such an administration? Alternatively, if the method’s practitioner isn’t going to change dosing or the agent itself, why bother collecting samples and performing an analysis as it is simply wasted effort and busywork since from the subject’s point of view no change in treatment occurs?
Claim 53 recites various “therapeutic agents” but it is unclear if the recited agents are those of part (i), part (iv) or possibly both of independent claim 40. Given that more than one therapeutic agent is possible, proper antecedent basis is lacking as it is unclear which therapeutic agent is to be limited by dependent claim 53.
It should be noted that all claims are joined to this rejection as no single claim resolves all of the issues present in the independent claim, and indeed most dependent claims fail to add any limitation obviating the problems of the independent claim. Amending the claims to more clearly and unambiguously identify that which applicant seeks to claim is one possible way to remedy the instant grounds of rejection.
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 40-59 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 broadly claimed methods for evaluating treatment of a plasma kallikrein (pKal)-mediated disorder, such a method comprising the steps of contacting a biological sample obtained from a subject before, after and/or during treatment with a “capture reagent”, 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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It should be pointed out that step (iii) requires comparison of data from samples collected BEFORE treatment with those taken during treatment, after treatment, or both during and after treatment, yet step (i) as presently written allows for seven collection possibilities due to the “and/or”, namely 1) only before, 2) only during, 3) only after, 4) before and during, 5) before and after, 6) during and after, and 7) before, during, and after. As such artisans cannot practice the full breadth of what is presently claimed as some recited possibilities for sample collection are incompatible with data analysis steps required later in the claim and thus many embodiments are impossible to practice. Additionally, step (iv) compels the method’s practitioner to administer a therapeutic agent to a subject identified as “not responsive” in step (iii) yet if step (iii) is actually practiced the subject must already have been given a therapeutic agent so as to obtain “during” and/or “after” subject samples. 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.
Issues are also present with regard to the subject upon whom the claimed method is practiced. Independent claim 40 recites “pKal-mediated disorder” with no further limitation in the claim itself. The specification provides exemplification of things encompassed by “pKal-mediated disorders” through the use of “in some embodiments” and “e.g.” on pages 6 and 20 for example, but such guidance is not an exhaustive definition. This is extremely problematic as applicant has claimed
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Thus the method is to be practiced on someone who has an unidentified disease/condition before they show any clinical sign or symptom of the unknown disease as there is no history even suggesting they might have the unknown disease, whatever it might be. While some conditions, such as hereditary angioedema, readily identify patients who might be a risk even if the patient presently has no symptoms based upon data obtainable form other family members such as parents and siblings, how is an artisan to identify someone who shows no signs of something that is unknowable and thus practice the claimed methods upon them? While diseases including hereditary angioedema are autosomal dominant with variable penetrance such that pedigree analysis can readily identify subjects who are “at risk” for development of the disease, it is completely unclear how artisans could ever identify someone at risk for a disorder when the disorder in question isn’t identified or defined. Note further that preemptively practicing the instant claimed methods upon absolutely everyone in the whole world also does not reasonably count as providing artisans with guidance and direction concerning how to practice that which has been claimed. Dependent claim 49 recites things that applicant believes to be “pKal-mediated disorders”, and while some of them are clinically defined and reasonably correlated with C1-INH deficiencies, other are not. For example, “head trauma” is listed as a pKal-mediated disorder, yet head trauma typically is caused by environmental damage such as occurs in a car crash or getting hit in the head by a soccer ball or an errant fastball at a baseball game and thus the injury has absolutely nothing to do with pKal in the patient. Similarly, claim 49 also recites “respiratory disease”, and the most ubiquitous respiratory disease is lung cancer which in the vast majority of cases is caused by smoking cigarettes, not by pKal. Down syndrome/trisomy 21 has significant neurological complications (Murugesan et al., see entire document) but indicating that such a neurological disease is mediated by pKal and can reasonably be treated by administering an agent that will increase C1-INH in the absence of solid supporting data is laughable at best.
With regard to the administered “therapeutic agent”, in addition to issues surrounding how many distinct “agents” are required by the claimed inventions as discussed earlier, 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.
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 compare 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.
No claims are allowable.
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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Michael Szperka
Primary Examiner
Art Unit 1641
/MICHAEL SZPERKA/Primary Examiner, Art Unit 1641
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