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 .
1. Formal Matters
A. Applicant’s election without traverse of Group I, drawn to the species n-11 and n-111, in the reply filed on 12/8/25 is acknowledged. Therefore, this restriction is deemed proper and is made FINAL.
B. Claims 1-12 and 14-20 are pending. Claims 10-12, 16 and 17 are withdrawn as being drawn to non-elected inventions. Claims 1-9, 14, 15 and 18-20 are the subject of this Office Action.
2. Claim Objections
Claim 14 is objected to since the use of the antibody for the general purpose of “in medicine” is not clear. See also the rejection under 35 USC 101, below.
3. Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 14, 15, 18 and 19 are rejected under 35 U.S.C. 101 because the claimed invention lacks patentable utility. The claims are drawn to the non-statutory phrase of “a use” and do not set forth any steps involved in the process, results in an improper definition of a process, i.e., results in a claim which is not a proper process claim under 35 U.S.C. 101. See for example Ex parte Dunki, 153 USPQ 678 (Bd.App. 1967) and Clinical Products, Ltd. v. Brenner, 255 F. Supp. 131, 149 USPQ 475 (D.D.C. 1966). The claims can be amended to, for example, “A method of”.
4. 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.
Claim 14 recites the limitation "antibody". There is insufficient antecedent basis for this limitation in the claim.
5. Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1 and 4-6 are rejected under 35 U.S.C. 103 as being unpatentable over Harris et al. in view of de Maat et al. (reference 6 on the IDS filed 3/7/23)
Harris et al. teaches monoclonal antibodies which bind FXII and also determine their binding sites of FXII (paragraph bridging pages 970 and 971; Table 2; page 973 under “Enzyme-linked immunosorbant assay for the detection of FXII antibody epitope-binding sites using generated peptides”).
Harris does not specifically teach that the binding epitope for the monoclonals comprises a conformational epitope. However, Harris uses ELISAs for epitope detection. As taught by Grace Bio-Labs (not used as part of the rejection, but to show the properties of an ELISA), “ELISA can be used to detect native proteins, and protein interactions that require intact three-dimensional structure” and “ELISA assays are very useful for looking at protein interactions that require native conformation, and for studying binding competition.” (see section entitled “ELISA assays”). Therefore, ELISAs would detect antibodies which bind the conformational epitope of claim 1. Given this, absent evidence to the contrary, the antibodies of Harris, which were determined using ELISA, would bind conformational epitope(s) of FXII.
Harris does not teach nanobodies. However, de Maat does teach producing nanobodies from llama (page 459, right column under “Llama immunization and bacteriophage library preparation”). It is noted that the nanobodies of de Maat are to FXIIa (the activated form of FXII), as opposed to the non-active FXII. Regardless, the technique would have still been obvious depending on the desired studies. It is also noted that de Maat also determine nanobody binding using ELISA (last paragraph of page 460 – “Nanobody capture ELISA for FXIIa”).
Regarding claim 4, though neither Harris nor de Maat teach the molar ratio, it would have been obvious at the time to produce a molar ratio that has as high as a blocking efficiency as possible, or as desired, in order to inhibit the maximal/desired FXII activity. [W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 454, 105 USPQ 223,235, (CCPA 1955). Furthermore, "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989) (determination of suitable dosage amounts in diuretic compositions considered a matter of routine experimentation and, therefore, obvious) and E.I. DuPont de Nemours & Co. v. Synvina C.V., 904 F.3d 996, 1006 (Fed. Cir. 2018) (“it is not inventive to discover the optimum or workable ranges by routine experimentation.”).
Regarding claim 5, though de Maat teaches llama instead of alpaca, both of these are camelids which produce nanobodies. Regarding claim 6, recombinant nanobody production is also taught by de Maat under “Llama immunization and bacteriophage library preparation”.
B. Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Harris et al. in view of de Maat et al. further in view of Clark et al. and further in view of Hofman et al.
The teachings of Harris and de Maat are seen in paragraph A, above. Neither teaches binding the fibronectin type II and kringle domains. However, Clark teaches that the fibronectin type II domain shields the activation loop of FXII, ensuring zymogen quiescence (Abstract). Clark does not teach the kringle domain. However, Hofman does teach that this domain is also a regulator of zymogen quiescence (Title; page 370, left column, first full paragraph) Given this, it would have been obvious to target these domains in order to prevent activation of FXII in order to regulate activities such as plasma contact activation.
C. Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Harris et al. in view of de Maat et al. further in view of Didiasova et al.
The teachings of Harris and de Maat are seen in paragraph A, above. Neither teaches inhibiting FXII without blocking FXIIa. However, Figure 3 of Didiasova teaches that FXII and FXIIa have distinct roles. Therefore, given the goal of the investigator, it would have been advantageous to have inhibited FXII without blocking FXIIa.
D. Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Harris et al. in view of de Maat et al. further in view of Bannas et al.
The teachings of Harris and de Maat are seen in paragraph A, above. Neither teaches nanobodies fused to Fc. However, Bannas does and states that these nanobody-Fc chimeras combine advantageous features of both in about half the size of a conventional antibody (Abstract).
Huang, though not being used as part of the rejection, is provided in order to elucidate the inherent characteristics of Fc fusions (Abstract; Introduction).
E. Claims 14, 15 and 18-20 are rejected under 35 U.S.C. 103 as being unpatentable over Harris et al. in view of de Maat et al. further in view of Matafonov (reference 3 on the IDS filed 3/7/23).
For the purposes of this rejection, claim 14 is being interpreted as a nanobody, not an antibody. The teachings of Harris and de Maat are seen in paragraph A, above. Neither teaches preparing an antithrombotic drug or a pharmaceutical composition. However, Matafonov does teach that FXII inhibition reduces thrombus formation in a primate model (Abstract), which also meets the limitation of “pharmaceutical composition” (see also page 1741 under “Mouse thrombosis model” and “Baboon thrombosis model”). Therefore, it would have been obvious to have used the nanobody inhibitor of Harris in view of de Maat in the method of Matafonov.
Though none of the reference teach an antivasculitis or IRI drug, instant claims 18 and 19 are drawn to a use of the nanobody to produce a drug for these purposes, not for a method of treating these conditions. The combination of cited references would have provided this drug regardless of whether or not the intended uses were known. Case law has established that a compound and all of its properties are inseparable, as are its processes and yields (In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963)).
F. Claims 14, 15 and 18-20 are rejected under 35 U.S.C. 103 as being unpatentable over Harris et al. in view of de Maat et al. further in view of Nickel et al.
For the purposes of this rejection, claim 14 is being interpreted as a nanobody, not an antibody. The teachings of Harris and de Maat are seen in paragraph A, above. Neither teaches preparing an IRI drug or a pharmaceutical composition. However, Nickel does teach that FXII inhibition can prevent IRI. Therefore, it would have been obvious to have used the nanobody inhibitor of Harris in view of de Maat in the method of Nickel. Though Nickel does not teach a pharmaceutical composition comprising an FXII inhibitor, it would have been obvious to have placed the inhibitor of Harris and de Maat into a pharmaceutical composition.
Though none of the reference teach an antithrombotic or antivasculitis, instant claims 18 and 19 are drawn to a use of the nanobody to produce a drug for these purposes, not for a method of treating these conditions. The combination of cited references would have provided this drug regardless of whether or not the intended uses were known. Case law has established that a compound and all of its properties are inseparable, as are its processes and yields (In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963)).
6. Conclusion
A. Claims 1-7, 14, 15 and 18-20 are not allowable.
B. Claims 8 and 9 are objected to since they depend from rejected base claim 1.
Advisory information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT S LANDSMAN whose telephone number is 571-272-0888. The examiner can normally be reached M-F 8 AM – 6 PM (eastern).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama, can be reached at 571-272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ROBERT S LANDSMAN/Primary Examiner, Art Unit 1647