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 .
Status of the Claims
Claims 30 and 34-44 are currently pending in the Application and are examined on the merits below.
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.
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.
Claim(s) 30-31 and 34-44 are rejected under 35 U.S.C. 103 as being unpatentable over Schranz et al (WO2017100679A1).
Amended claim 30 is directed to a method of treating a human suffering from HAE attack or reducing the rate of HAE attack in a human subject through administration of an antibody as described below at about 300mg every two weeks. The subject is described as having suffered at least one prior laryngeal attack before administration of the antibody. The method functionally reduces the occurrence of HAE attacks in the selected patient cohort by greater than 85%.
Amended claim 30 incorporates limitations of cancelled claim 33 importantly SEQ ID NO: 11 and SEQ ID NO: 12 as the sequences of the heavy and light chain of previously disclosed antibody DX-2930 (with signal sequences removed). As previously presented the disclosure of Schranz provides sequences that are identical to instant SEQ ID NO: 1 and SEQ ID NO:2 as reference SEQ ID NO: 1 and 2 (heavy and light chains of antibody DX-2930 respectively). The disclosure of Schranz provides annotated SEQ ID NO:1 and 2 sequences wherein Italicized amino acid residues are signal peptide with the remainder of the amino acid sequences 100% identical to SEQ ID NO: 11 and 12. Thereby the disclosure of Schranz provides sequences identical to the instant sequence 11 and 12 (p18-19).
Regarding claim 30 and the patient cohort as subjects suffering from one or more prior laryngeal attacks before administration of the antibody, as well as the particular dosing scheme administered as 300mg every two weeks, the disclosure of Schranz describes that HAE (hereditary angioedema) is a disease in which 50% of subjects will experience laryngeal attack in their lifetime (p31 “hereditary angioedema”). The disclosure of Schranz indicates that HAE may be treated with DX-2930, and that DX-2930 may be given at 300mg every two weeks (p37 second paragraph, p38-p39). The disclosure provides studies in which subjects are administered the DX-2930 for treating HAE (examples 1, example 2).
It would thus be obvious to utilized the DX-2930 antibody in subjects which have previously experienced a laryngeal attack as indicative of the subject suffering from the HAE disease. The subjects would benefit from the inhibition of plasma kallikrein through antagonistic binding of the DX-2930 to the specific active kallikrein epitope. Thus C1 esterase inhibitory enzyme activity is augmented through plasma kallikrein inhibition. Beneficial reduction in the rate of HAE attack or abrogation of HAE attack are thus achieved. Reduction in the rate of HAE attacks by greater than 85% in the selected patient cohort is a latent/inherent property of the structural components and method parameters made obvious by Schranz.
With respect to claims 34-36 the disclosure of Schranz describes the pharmaceutical composition of the antibody DX-2930 or fragments thereof to consist of sodium phosphate 30mM, citric acid 19mM histidine at 50mM, NaCl at a concentration of 90mM and polysorbate 80 at a concentration of 0.01%.(p26 and claims 45-46, p67).
With respect to claim 37 the disclosure of Schranz indicates that the therapeutic antibody of the invention may be preferably administered subcutaneously (p1, last paragraph; p2, 4th paragraph).
With regards to claim 38 the disclosure of Schranz indicates that HAE that is treated may be type I or type II HAE (p 2, last paragraph).
With regards to claim 39 the disclosure of Schranz indicates that subjects may have received prior treatment (p3, paragraph 2) which with respect to claims 40 and 41 may comprise a c1-esterase inhibitor (c1-INH) for example (p3, paragraph 2).
With respect to claim 42 and 43 the disclosure of Schranz indicates that a tapering period may be applied with respect to previously administered, maintained HAE treatments, and the tapering period may range from 2-4 weeks (p3, paragraph 2).
With regards to claim 44, antibody of the invention of Schranz may be IgG antibody for example (p14, paragraph 1; p16, last paragraph).
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 30 and 34-44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-19 of U.S. Patent No. 11,286,307 in view of Schranz. The claims of the reference patient indicate the treatment of subjects suffering HAE with antibody which is identical to those of the instant claims (see claim 1, 4, 8). The treatment method indicates that subjects may be treated with the antibody for prevention of attacks of HAE. The disclosure describes specific treatment of 300mg every two weeks as in the instant application claim 1. Thus considering the disclosure of Schranz which describes that 50% of HAE subjects suffer laryngeal attacks and the usefulness of doing thus it would be obvious to include subject which have had a laryngeal attack as those who suffer from the disease.
Claim 30 and 34-44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11084884 in view of Schranz. The reference patent describes methods of treating HAE with antibody that comprise the CDR regions of the DX-2930 antibody or the DX-2930 antibody for example (claims 1, 12-17) at doses that are identical for example 300mg every 4 weeks, 300mg every 2 weeks, (claims 4, 5) to those of the instant application. The additional disclosure of Schranz for instance provides the further limitations as described above of treating subjects which may have previously suffered laryngeal attack manifestation of the HAE disease.
Claim 30 and 34-44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 8816055 in view of Schranz. The claims of the reference patent describe antibody identical to that of the instant claimed method. The disclosure of Schranz further provides the limitations of the instantly claimed antibody as well as methods and formulation as indicated above.
Claims 30 and 34-44 rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-6 of U.S. Patent No. 9266964 in view of Schranz. The claims of the reference patent indicate a method of treating a plasma kallikrein associated disorder in a subject through administration of an antibody which is identical to that of the instant claims. The further disclosure of Schranz indicates that the HAE may be treated or prophylactically treated through the administration of the same antibody , and teaches that attacks of laryngeal nature occur in about 50% of subjects. It would thus be obvious to treat the subjects of the instant claims with the identically disclosed antibody/method for the purpose of avoiding prophylactically the occurrence of additional HAE attacks in those known to suffer from the disease.
Response to Arguments- Claim Rejections - 35 USC § 112
Applicant has cancelled previously rejected claim 31 and therefore the previously applied rejection is removed.
Response to Arguments- Claim Rejections - 35 USC § 103
In reply to the previously presented rejection Applicant amends the instant claim 30 to describe that the claimed method of administration results in a greater that 85 % reduction in HAE attack rate in subjects relative to the placebo subject cohort. Thereafter the Applicant initially argues that the prior art does not include each element of the amended claims particularly the limitation that the claimed method results in greater than 85% reduction in HAE attack rates compared to placebo when the antibody is administered at the claimed dose of 300mg every 2 weeks. In further arguments the Applicant also describes that it would not be predictable that the elements presented in the methods of Schranz would predictably result in a patient cohort which comprises subjects which have had a prior laryngeal attack. Because of these reasons Applicant indicates that a prima facie case of obviousness over Schranz has not been established.
Regarding the arguments presented and the instantly-claimed method the disclosure of Schranz clearly describes that subjects may be treated with the claimed structure of DX2930 every 2 weeks at 300mg as indicated in previously applied rejections and above. Furthermore the disclosure of Schranz recognizes that 50% of subjects which suffer from HAE will suffer from a laryngeal (severe) attack in their lifetime, thus subjects included in treatment cohorts of a significant N value, randomly selected for a therapeutic cohort (those who already have had HAE attacks) would include some which have had “severe disease” such as laryngeal attacks. Schranz provides for this contingency and thereby intends to include such subjects in the study protocol (Schranz p44 last paragraph). Thus considering that Schranz makes obvious the structural features of the method instantly claimed, the instantly claimed functional feature of efficacy in the subset of subjects which suffer from severe laryngeal HAE attacks are inherent features of the claimed method.
In summary it is found that the reference of Schranz clearly discloses that administration of DX-2930 antibody is appropriate for subjects which present with any symptom of HAE including severe life threatening laryngeal attack, a symptom which 50% of HAE subjects can expect to experience in their lifetime (p31-p32). Additionally figure 3 of Schranz discloses that the biomarker predictor for HAE attacks (2 chain HMWK ) is most effectively reduced by a dose of 300mg antibody approximately every 2 weeks. It would thus be expected that a higher dose of DX-2930 would be more likely to result in effective reduction of emergent HAE symptoms (such as the severe laryngeal attack) when compared to lower doses of the administered antibody.
Conclusion
Summary: No claims are allowed.
THIS ACTION IS MADE FINAL. 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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/BRIAN HARTNETT/ Examiner, Art Unit 1644
/DANIEL E KOLKER/ Supervisory Patent Examiner, Art Unit 1644