Detailed Actions
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Status of the Claims
Claims 51, 52, 59, 60 and 63-65 are currently pending and under consideration.
Withdrawn Objections
In view of Applicant’s amendment to claim 59 the claim objection is hereby withdrawn.
Withdrawn Rejections
In view of Applicant’s arguments to claim 51 the 35 USC 112(a) rejection of claims 51, 52, 59, 60, and 63-65 regarding new matter is hereby withdrawn.
In view of Applicant’s amendments to claim 51 to remove “the subject”, “the disorder”, removing the preamble, the 35 USC 112(b) rejection of claim 51 is withdrawn with regards to these particular ambiguities; however, it is noted claim 51 remains rejected under 35 USC 112(b) for the reasons set forth below.
In view of Applicant’s arguments, the 35 USC 112(b) rejection of claims 52 and 59 regarding antecedent basis of "the level" is hereby withdrawn.
In view of Applicant amending claim 64 to depend from claim 59 the 35 USC 112(b) rejection of claim 64 is hereby withdrawn.
In view of Applicant amending claim 51 to recite “a reference value” the 35 USC 112(b) rejection of claim 65 is hereby withdrawn.
Claim Rejections - 35 USC § 112(a)
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.
Written Description
Claim 51, 52, 59, 60, and 63-65 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 51 is drawn to “wherein the detection agent specifically binds cleaved HMWK as compared to intact HMWK” (see lines 12-13). The specification defines “specifically binds” as reacting or associating more frequently, more rapidly, with greater duration and/or with grater affinity with a particular target antigen than it does with alternative targets (see specification pg. 28 last para). In addition, the term does not necessarily require (although it can include) exclusive binding (see specification pg. 29, 1st para). Therefore, the language of claim 51 encompasses a genus of antibodies with any degree of increase in binding frequency, rate of association, length of binding, or strength of binding to cleaved HMWK compared to intact HMWK. Furthermore, claim 51 is drawn to a second function, i.e., antibodies that also bind the C-terminus of the light chain of cleaved HMWK (see claim 51 lines 14-15). It is noted the specification teaches the C-terminus of cleaved HMWK is identical to intact HMWK (see figure 4).
Applicants have disclosed murine anti-HMWK (11H05) antibody has a “higher sensitivity” to intact HMWK under reducing conditions as compared to cleaved HMWK (see specification pg. 56 last para, figure 5A and B). Therefore, Applicants have not disclosed a single antibody that preferentially binds cleaved HMWK as compared to intact HMWK as instantly claimed. Applicant also discloses intact HMWK is a single polypeptide whereas cleaved HMWK is a 2 chain structure comprising a heavy and light chain linked via a disulfide bond (see specification figure 4). Furthermore, bradykinin a vasodilator is cleaved from intact HMWK (see specification 1, last para). The ordinary artisan would understand there are structural differences between intact and cleaved HMWK which would contribute to the unpredictability of making antibodies that exhibit a preference for cleaved HMWK.
Antibodies with the instantly claimed preferential binding are not known in the art. The closest antibody with the instantly claimed functions is a post filing patent (i.e., 2016) which discloses anti-HMWK antibody 559B-M0004-B04. The antibody binds preferentially to cleaved HMWK and not intact HMWK; however, the ‘747 patent also teaches the antibody specifically binds to the N-terminally located domain 5 (see ‘747 patent col. 47 Table 2, lines 36-37). While other anti-HMWK antibodies are disclosed the ‘747 patent, the patent is silent as to the claimed preferential binding (e.g., rate of association, length of binding) to cleaved HMWK as compared to intact HMWK. Thus, there are no known antibodies with the instantly claimed functional properties. Therefore, the instant specification “claims merely recite a description of the problem to be solved while claimed all solutions to it and… cover any compound later actually invented and determined to fall within the claim’s functional boundaries— leaving it to the pharmaceutical industry to complete an unfinished invention.” Ariad Pharmaceuticals, Inc. v. Eli Lilly and Co., 598 F.3d 1336, 1353 (Fed. Cir. 2010).
Without a correlation between structure and function, the claim does little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (“definition by function … does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is”). Furthermore, Applicant has not disclosed a representative number of species of the claimed genus.
In conclusion, Applicant has not described the claimed invention sufficiently to show they had possession of the claimed genus of anti-HMWK antibodies that preferentially binds cleaved HMWK and also bind to the C-terminus of the light chain of cleaved HMWK in terms of binding frequency, rate of association, length of binding, or strength of binding.
Applicants’ arguments filed 2 July 2026 (referred to herein as Remarks) have been fully considered but they are not persuasive.
Applicant argues antibody 11H05 is within the scope of an antibody that “specifically binds cleaved HMWK as compared to intact HMWK; wherein the detection agent is an antibody that binds the c-terminus of the light chain of cleaved HMWK” and points to example 3 for support (see claim 51; see Remarks pg. 8, 1st full para). In addition, Applicant argues method claims can meet the written description requirement when the invention is a method that uses the established antibodies and not in the antibodies themselves (see Remarks pg. 8, 2nd full para).
First, the specification discloses antibodies that preferentially identify cleaved HMWK from LMWK as LMWK does not contain the c-terminal fragment of the light chain of cleaved HMWK (see pg. 28, 2nd full para, pg. 33, first full para). Example 3 discloses 11H05 binds the light chain of HMWK and not the heavy chain of HMWK and this is preferrable because the antibody does not bind LMWK (see specification pg. 54, 1st para). There is nothing to suggest antibody 11H05 has selective binding or exclusive binding to cleaved HMWK. In fact, figure 4A and 4B demonstrate 11H05 binds both intact and cleaved HMWK (see lanes 1 and 2). Therefore, as previously stated 11H05 is not within the scope of the antibody with the claimed functional property for the reasons made of record.
Second, even if 11H05 were within the scope of the claimed functional properties (which the examiner does not concede) this would amount to a single antibody and therefore insufficient to “establish a genus” of antibodies with the claimed functional properties.
Therefore, for the reasons made of record the 35 USC 112(a) rejection for written description of claims 51, 52, 59, 60, and 63-65 is hereby maintained.
Claim Rejections - 35 USC § 112(b)
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 51, 52, 59, 60, and 63-65 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.
It is noted the 35 USC 112(b) rejection set forth below has been amended in part in view of Applicant’s amendment to claim 51.
The scope of the identification step of claim 51 is unclear. Given the claim is drawn to a subject that has a disorder that is associated with contact system activation (see lines 3-4) it is unclear how the disorder can be identified a second time after the measuring step when the disorder was identified during subject selection. In addition, it is unclear if the wherein identification clause (i.e., last two lines) is directed to identifying a subset of subjects with the claimed disorders that also have elevated contact system activation or alternatively identifying the disorder itself from elevated contact system activation.
Claim 51 is drawn to “wherein the detection agent is an antibody that binds to the C-terminus of the light chain of cleaved HMWK” (see claim 51 lines 14-15). It is unclear what is considered the C-terminal region. For example, is an antibody that binds to any location in domain 6 within the scope of or is an antibody that binds only a portion of domain 6 within the scope of the “C-terminus of the light chain”. The specification teaches cleaved and intact HMWK have identical structure, i.e., domain 6, therefore it is unclear how an antibody can preferentially bind the C-terminus of cleaved HMWK as compared to intact HMWK when they have identical structure. In so far as Applicant argues the c-terminal region of a protein is understood by the ordinary artisan (see Remarks pg. 11, 1st para) is not persuasive. Applicant provides no reference to support such an assertion that the ordinary artisan would understand which portions of the light chain of HMWK fall within the scope of the c-terminal region in the context of epitope binding. Second, Applicant has asserted “The claim does not imply that the antibody specifically binds the c-terminus of cleaved HMWK as compared to the c terminus of intact HMWK” (see Remarks pg. 11, 2nd para); however, this is exactly what the claim recites,
“wherein the detection agent specifically binds cleaved HMWK as compared to intact HMWK; wherein the detection agent is an antibody that binds to the C-terminus of the light chain of cleaved HMWK” (claim 51 lines 10-13).
Therefore, it is unclear to the Examiner what Applicant is trying to argue.
Therefore, the 35 USC 112(b) rejection of claims 51, 52, 59, 60 and 63-65 is hereby maintained for the reasons set forth above and the reasons made of record.
Conclusion
No claim 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.
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/H.A.P./ Examiner, Art Unit 1644
/AMY E JUEDES/ Primary Examiner, Art Unit 1644
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