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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on April 29, 2026 has been entered.
Status of the Claims
Claims 1-15 were originally filed December 5, 2023.
The amendment received November 22, 2024 amended claim 1.
The amendment received September 4, 2025 amended claims 1-8.
The amendment received April 29, 2026 amended claims 1, 3, 5-8; canceled claim 2; and added new claims 16 and 17.
Claims 1 and 3-17 are currently pending.
Claims 1, 3-5, 8, and 17 are currently under consideration.
Election/Restrictions
Applicants’ elected, without traverse, SLLR (SEQ ID NO: 28) and hereditary angioedema as the species in the reply filed on November 22, 2024. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Claims 6, 7, and 9-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on November 22, 2024.
The specification states that SLLR (SEQ ID NO: 28) reads on the functions of claims 3-5.
Claims 6, 9, 10, and 16 are withdrawn because a modification at P1’ was not elected.
Claim 7 is withdrawn because a modification that reduces susceptibility to oxidation was not elected (e.g. P8 in the specification).
Priority
The present application claims status as a DIV of 16/487,858 filed August 22, 2019 (now U.S. Patent 11,851,474) which is a 371 (National Stage) of PCT/EP2018/054490 filed February 23, 2018 which claims foreign priority to EP 17157527.7 filed February 23, 2017.
Please note: the present application is a CON of 16/487,858 filed August 22, 2019 (now U.S. Patent 11,851,474) since the restriction requirement was withdrawn and the method claims were rejoined at the time of allowance.
Please note: applicants agreed that the present application is a CON. See the response received September 4, 2025 (see page 8, first paragraph and page 6, section 3). Also see the ADS submitted September 4, 2025.
Interview
Applicants’ representative provided a “SUMMARY OF INTERVIEW” on September 4, 2025. Below is the examiner of record’s comments regarding the summary.
As discussed in the interview, recovery of breadth of scope may not be possible due to the prior art (see art rejections below). In addition, certain mutations in the RCL were canceled during prosecution in the parent due to the art rejections of record (i.e. only allowable RCL mutations are present in the parent claims which were allowed).
It was agreed during the interview that if the independent claim was modified to recite a full length modified a1 antitrypsin, that the amendment would be examined.
At no point in the interview did the examiner of record state that modified RCLs of SEQ ID NOs: 12-28 in a full length a1 antitrypsin would render the rejections of record moot. See the art rejections below. Furthermore, it is unclear why applicants would cancel SEQ ID NOs: 12, 18, 23-25, and 27 if this were the case (see the claim amendments received September 4, 2025).
At no point in the interview did the examiner of record state that claim 8 would be allowable if the method specified in claim 1 is sufficiently limited to define the modified full length a1 antitrypsin wherein the RCL are defined.
Due to applicants’ representative’s mischaracterization of the interview, no future interviews will be granted and all communication will be in written form and part of the record.
Sequence Interpretation
The Office interprets claims comprising SEQ ID NOs: in the following manner: “comprising a sequence of SEQ ID NO: 1” requires only a 2mer of SEQ ID NO: 1, “comprising the sequence of SEQ ID NO: 1” requires the full-length sequence with 100% identity to SEQ ID NO: 1 with any N-/C-terminal additions or any 5’/3’ additions, “consisting of SEQ ID NO: 1” requires the full-length sequence with 100% identity to SEQ ID NO: 1 and the same length as SEQ ID NO: 1, and “selected from the group consisting of SEQ ID NOs: 1, 2, and 3” requires the full-length sequence with 100% identity to SEQ ID NOs: 1, 2, or 3 and the same length as SEQ ID NOs: 1, 2, or 3. Any claim requiring a specific percent identity, necessarily requires at least the recited percent identity.
Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
It is unclear why the clean and marked up specifications received September 4, 2025 are labeled “Sequence Listing”.
Withdrawn Objections
The objection of claim 8 regarding the extra common in line 12 should be removed is withdrawn in view of the amendment received April 29, 2026.
The objection to claim 2 regarding “wild-type serpin a1 AT” should read “wild-type a1 antitrypsin” to correlate with the claims (i.e. serpin not utilized, acronym should be defined with the first usage and/or not utilized) is withdrawn in view of the amendment received April 29, 2026 which canceled claim 2.
The objection to claim 3 regarding “unmodified serpin” should read “unmodified a1 antitrypsin” to correlate with the rest of the claims is withdrawn in view of the amendment received April 29, 2026.
The objection to claim 5 regarding the conjunction should be “and/or” to correlate with “at least one” is withdrawn in view of the amendment received April 29, 2026.
New Objections Necessitated by Amendment
Claim Objections
Claim 1 is objected to because of the following informalities: “and” should read “and/or” to correlate with one or more (see lines 4, 9, 10). Appropriate correction is required.
Claim 17 is objected to because of the following informalities: “and” should read “and/or” to correlate with one or more (see lines 3, 4, 9, 10). Appropriate correction is required.
Specification
The amendment filed April 29, 2026 is objected to under 35 U.S.C. 132(a) because it introduces new matter into the disclosure. 35 U.S.C. 132(a) states that no amendment shall introduce new matter into the disclosure of the invention. The added material which is not supported by the original disclosure is as follows: withdrawn claim 7.
Applicant is required to cancel the new matter in the reply to this Office Action.
Withdrawn Rejections
The rejection of claim 1 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 (lack of antecedent basis) is withdrawn in view of the amendment received April 29, 2026.
The rejection of claim 2 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 is withdrawn in view of the amendment received April 29, 2026 wherein claim 2 was canceled.
The rejection of claims 1-5 and 8 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 is withdrawn in view of the amendment received April 29, 2026.
Maintained and/or Modified* Rejections
*wherein the modification is due to amendment
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 3-5 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claims 3 and 4 depend on independent claim 1 and claim 5 depends on claim 4. Independent claim 1 requires a full length a1 antitrypsin with modifications in one or more of residues of positions P4, P3, P2, P1, P1’, and P8 including SEQ ID NO: 28 in the RCL administered to a subject. The specification clearly teaches that SEQ ID NO: 28 has all of the functions of dependent claims 3-5. Therefore, dependent claims 3-5 do not alter the method steps or the reagents utilized in the method and fail to further limit the method. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
SEQ ID NO: 13 reads on claims 3-5; SEQ ID NO: 14 reads on claims 3-5; SEQ ID NO: 15 reads on claims 3-5; SEQ ID NO: 16 reads on claims 3-5; SEQ ID NO: 17 reads on claims 3-5; SEQ ID NO: 19 reads on claims 3-5; SEQ ID NO: 20 reads on claims 3-5; SEQ ID NO: 21 reads on claims 3-5; SEQ ID NO: 22 reads on claims 3-5; SEQ ID NO: 26 reads on claims 3-5; and SEQ ID NO: 28 reads on claims 3-5 (see Table 1 pages 32-33).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 112(d) as failing to further limit for claims 3-5 were considered but are not persuasive for the following reasons.
Applicants contend that “only one of the possible modified full-length a1 antitrypsin defined in claim 1 has an RCL with positions with residues P4, P3, P2 and P1 defined as SLLR (SEQ ID NO: 28)”. Applicants also contend that “The other possible modified full-length a1 antitrypsins defined in claim 1 may or may not have all of the functions recited in dependent claims 3-5. Thus, claims 3-5 are narrower in scope than claim 1 since the functions of the modified full-length a1 antitrypsins are more narrowly defined.”.
Applicants’ arguments are not convincing since it is applicants responsibility to clearly claim the presently utilized reagents. If applicants do not know the function of each modification at residues P4, P3, P2, P1, P1’, and P8, then how is the examiner of record or the American public to know which modifications read on the present functions. Thus, it appears that the recited functions do not narrow the claim scope (e.g. modifications may be any or all of the recited functions in claims 3-5).
SEQ ID NO: 13 reads on claims 3-5; SEQ ID NO: 14 reads on claims 3-5; SEQ ID NO: 15 reads on claims 3-5; SEQ ID NO: 16 reads on claims 3-5; SEQ ID NO: 17 reads on claims 3-5; SEQ ID NO: 19 reads on claims 3-5; SEQ ID NO: 20 reads on claims 3-5; SEQ ID NO: 21 reads on claims 3-5; SEQ ID NO: 22 reads on claims 3-5; SEQ ID NO: 26 reads on claims 3-5; and SEQ ID NO: 28 reads on claims 3-5 (see Table 1 pages 32-33).
Claim Rejections - 35 USC § 112
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 1, 3-5, 8, and 17 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. This is a written description rejection.
Independent claim 1 is drawn to a method for treating a bradykinin-mediated disease comprising administering a modified full length a1 antitrypsin comprising one or more modifications at positions P4, P3, P2, P1, P1’, and/or P8 including wherein P4-P1 are SEQ ID NOs: 13-17, 19-22, 26, and 28. The invention as claimed encompasses all known a1 antitrypsin and all potential a1 antitrypsin with a single point mutation in any one of P4, P3, P2, P1, P1’, and/or P8. The present claim does not require SEQ ID NOs: 13-17, 19-22, 26, and 28 since P4, P3, P2, P1, P1’ or P8 alone could be modified to anything. The present modification is broader in scope than a mutation and includes, deletions, additions, PEGylation, other modifications, etc. In addition, the claim reads on any subject with any disease associated directly or indirectly with bradykinin. For example, it is unclear which specific modifications would result in treating a bradykinin-mediated disease or the function of increased inhibition of PK (independent claim 1), increased inhibition of FXII (dependent claims 3 and 4), inhibits plasmin, FXII, or APC (dependent claim 5). Furthermore, some mutations in a1 antitrypsin actually cause disease, therefore, it is unclear why those mutations would be included in the claims.
The specification does not teach a single in vitro study regarding a bradykinin-mediated disease cell line model, nor does the specification teach a single in vivo animal model for treatment of a bradykinin-mediated disease model much less the myriad of diseases recited in claim 8. Therefore, one skilled in the relevant art would not reasonably conclude that the Applicants had possession of the invention as claimed.
See Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See page 1116.).
Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. In Fiddes v. Baird, 30 USPQ2d 1481, 1483, claims directed to mammalian FGF's were found unpatentable due to lack of written description for the broad class wherein the specification provided only the bovine sequence.
Additionally, Cf. University of Rochester v G.D. Searle & Co., Inc., Monsanto Company, Pharmacia Corporation, and Pfizer Inc., No. 03-1304, 2004 WL 260813 (Fed. Cir., Feb. 13, 2004) held that:
Regardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to that subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 112(a) (written description), for claims 1, 3-5, 8, and 17 were considered but are not persuasive for the following reasons.
Applicants contend that the well-known sequence of full-length a1 antitrypsin combined with SEQ ID NOs: 13-17, 19-22, 26, and 28 are enough to provide adequate written description. Applicants contend that the specification provides adequate date to provide adequate written description for the breadth of diseases recited in present claim 8.
Applicants’ arguments are not convincing since the amendment received April 29, 2026 broadened the scope of the “modifications” which can be at any one or more of P4, P3, P2, P1, P1’, and/or P8 (see claims 1 and 17). Thus, P4 can be modified alone, P3 can be modified alone, P2 can be modified alone, P1 can be modified alone, P1’ can be modified alone, and P8 can be modified alone. Thus, SEQ ID NOs: 13-17, 19-22, 26, and 28 are not required by the claim.
Figures 1, 2, 4, and 5 show inhibition of PK utilizing SEQ ID NO: 13 or 28 modifications (P4-P1) and various P1’ mutations. However, statistical analysis was not provided and it appears that some mutations of P1’ are not any better than wild type (i.e. would those mutations still read on the present claims). For Figures 1 and 2, it is assumed that wild type was utilized as a baseline and all graphed results are above wild type baseline. Otherwise, Figures 1 and 2 appear to show that all mutations are worse than wild type. Again, statistical analysis was not provided.
Figure 3 shows inhibition of FXIIa with various P1’ mutations. However, statistical analysis was not provided and it appears that some mutations are not any better than wild type (i.e. would those mutations still read on the present claims).
Figure 6 shows inhibition of thrombin with various P1’ mutations. However, statistical analysis was not provided and it appears that some mutations are not any better than wild type (i.e. would those mutations still read on the present claims).
Figure 7 shows inhibition of protein C with various P1’ mutations. However, statistical analysis was not provided and it appears that some mutations are not any better than wild type (i.e. would those mutations still read on the present claims).
Table 1 shows that SEQ ID NOs: 1317, 19-22, 26, and 28 all read on the functions of claims 3-5.
Therefore, individual modifications for P4, P3, P2, P1, and P8 were not tested. In addition, not all of the various modifications of P1’ have the presently disclosed functions.
Applicant has not shown that the originally filed specification provides adequate written description for all of the presently claimed modifications or the method of treating any bradykinin-mediated disease.
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 8 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of the myriad of diseases is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: the myriad of diseases have a myriad of causes, symptoms, etc.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Arguments and Response
Applicants’ arguments directed to the rejection regarding improper Markush group for claim 8 were considered but are not persuasive for the following reasons.
Applicants contend that all of the Markush members share a single structural similarity and a common use and refer to the “narrowly defined modified full-length a1 antitrypsin”.
Applicants’ arguments are not convincing since the Markush group does not include the more broadly defined modified full-length a1 antitrypsin wherein only one or more of P4, P3, P2, P1, P1’, and/or P8 are modified. The Markush group of claim 8 refers to a broad scope of various diseases which are characterized by different symptoms, causes, and treatments.
New Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 112
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 1, 3-5, 8, and 17 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. This is a new matter rejection.
The originally filed specification does not provide support for the genus of any modification to P8. P8 is only referred to on page 22 at lines 9-11. P8 (M351) is only replaced with I, L, or V.
Claims 1, 3-5, 8, and 17 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. This is a new matter rejection.
The originally filed specification does not provide support for the genus of a modification for any one or more of P4, P3, P2, P1, P1’, and/or P8. Modifications can include mutations, deletions, additions, PEGylation, etc. The only changes to P4, P3, P2, P1, P1’, and/or P8 are specific mutations.
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 1, 3-5, 8, and 17 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claims 1 and 17 recites the broad recitation “modified in one or more of residues of positions P4, P3, P2, P1, P1’, and P8”, and the claim also recites P4-P1 are selected from the group consisting of SEQ ID NOs: 13-17, 19-22, 26, and 28 which is the narrower statement of the range/limitation. The claims are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 3 is 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.
Claim 3 recites the limitation "mutations" in line 1. There is insufficient antecedent basis for this limitation in the claim. Independent claim 1 now refers to “modified” which is broader in scope.
Claims 3-5 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. One of skill in the art would not be able to determine the scope of the present claims. For example, it is unclear which modifications of one or more of P4, P3, P2, P1, P1’, and/or P8 would result in the various functions.
Claim 17 is 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. One of skill in the art would not be able to determine the scope of the present claims. For example, it is unclear what the scope of “has a sequence according to” is (e.g. open, closed, etc.).
New Rejection Necessitated by Amendment
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 3-5, 8, and 17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Huntington et al. U.S. Patent Application Publication 2016/0311887 published October 27, 2016.
For present claims 1, 3-5, 8, and 17, Huntington et al. teach methods of administering modified a1 antitrypsin (residues 25-418 of SEQ ID NO: 7; present SEQ ID NO: 1) wherein P4 is S, P2 is L, and P1 is R (i.e. SXLR of present SEQ ID NO: 28) to a subject wherein the subject has a disease associated with hemostasis, bleeding, hemorrhage, bleeding disorders, trauma, deficiencies in clotting factors, etc. (please refer to the entire specification particularly the abstract; paragraphs 2, 8-30, 34-63, 67, 116-120, 124, 144, 151-161, 169, 170, 191, 196-219, 241, 227, 244, 245, 292, 294, 295; Figures 1-15; Table 14). Huntington et al. also teach that the reactive center loop (RCL) of the serpin family is highly conserved and can be mutated at any position to alter activity (please refer to the entire specification particularly paragraphs 30-38). Huntington et al. teach that P17-P3’ is the RCL for a1-antitrypsin (please refer to the entire specification particularly paragraph 38). Huntington et al. also teach that P1’ can be mutated to Q, N, Y, I, M, V, R, H, K, C, A, S, or E; P1 can also be mutated to K; and P2 can also be mutated to Q, N, Y, I, V, R, K, or T (please refer to the entire specification particularly paragraphs 38-63).
Therefore, the presently claimed method is anticipated by Huntington et al.
Maintained and/or Modified* Rejections
*wherein the modification is due to amendment
Claim Rejections - 35 USC § 103
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.
Claims 1, 3-5, 8, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Huntington et al. U.S. Patent Application Publication 2016/0311887 published October 27, 2016 and Bock U.S. Patent Application Publication 2007/0259809 published November 8, 2007.
For present claims 1, 3-5, 8, and 17, Huntington et al. teach methods of administering modified a1 antitrypsin (residues 25-418 of SEQ ID NO: 7; present SEQ ID NO: 1) wherein P4 is S, P2 is L, and P1 is R (i.e. SXLR of present SEQ ID NO: 28) to a subject wherein the subject has a disease associated with hemostasis, bleeding, hemorrhage, bleeding disorders, trauma, deficiencies in clotting factors, etc. (please refer to the entire specification particularly the abstract; paragraphs 2, 8-30, 34-63, 67, 116-120, 124, 144, 151-161, 169, 170, 191, 196-219, 241, 227, 244, 245, 292, 294, 295; Figures 1-15; Table 14). Huntington et al. also teach that the reactive center loop (RCL) of the serpin family is highly conserved and can be mutated at any position to alter activity (please refer to the entire specification particularly paragraphs 30-38). Huntington et al. teach that P17-P3’ is the RCL for a1-antitrypsin (please refer to the entire specification particularly paragraph 38). Huntington et al. also teach that P1’ can be mutated to Q, N, Y, I, M, V, R, H, K, C, A, S, or E; P1 can also be mutated to K; and P2 can also be mutated to Q, N, Y, I, V, R, K, or T (please refer to the entire specification particularly paragraphs 38-63).
However, Huntington et al. do not teach modification of P3.
For present claims 1, 3-5, 8, and 17, Bock teaches methods of mutating P3 to L (i.e. residue 2 of present SEQ ID NO: 28) in serpins and utilizing the mutant serpin for treatment of bleeding disorders (please refer to the entire specification particularly the abstract; paragraphs 3, 5, 37, 38, 89, 90, 105, 108, 109, 112, 123, 125).
All the claimed elements (i.e. mutation of the RCL of serpins; utilizing mutated serpins to treat various bleeding disorders) were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because the substitution of one known element (i.e. a1 antitrypsin/serpin with mutated RCL at residues P4, P2, P1, and/or P1’) for another (i.e. serpin with a P3 mutation) would have yielded predictable results (i.e. ability to treat bleeding disorders) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. mutation of P3 to leucine in the RCL of serpins) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because a person of ordinary skill has good reason to pursue the known options within their technical grasp. If this leads to the anticipated success, it is likely the product no of innovation but of ordinary skill and common sense. See KSR International Co v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 103 as being unpatentable over Huntington et al. and Bock for claims 1, 3-5, 8, and 17 were considered but are not persuasive for the following reasons.
Applicants contend that since Huntington et al. teaches a1 antitrypsin and Bock et al. teaches ATIII, that one of skill in the art would not combine the references.
Applicants’ arguments are not convincing since the teachings of Huntington et al. and Bock render the method of the instant claims prima facie obvious.
Huntington et al. also teach that the reactive center loop (RCL) of the serpin family is highly conserved and can be mutated at any position to alter activity (please refer to the entire specification particularly paragraphs 30-38). Huntington et al. teach that P17-P3’ is the RCL for a1-antitrypsin (please refer to the entire specification particularly paragraph 38).
Claims 1, 3-5, 8, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Huntington et al. U.S. Patent Application Publication 2016/0311887 published October 27, 2016 and Felber et al., 2006, Mutant recombinant serpins as highly specific inhibitors of human kallikrein, FEBS Journal, 273: 2505-2514.
For present claims 1, 3-5, 8, and 17, Huntington et al. teach methods of administering modified a1 antitrypsin (residues 25-418 of SEQ ID NO: 7; present SEQ ID NO: 1) wherein P4 is S, P2 is L, and P1 is R (i.e. SXLR of present SEQ ID NO: 28) to a subject wherein the subject has a disease associated with hemostasis, bleeding, hemorrhage, bleeding disorders, trauma, deficiencies in clotting factors, etc. (please refer to the entire specification particularly the abstract; paragraphs 2, 8-30, 34-63, 67, 116-120, 124, 144, 151-161, 169, 170, 191, 196-219, 241, 227, 244, 245, 292, 294, 295; Figures 1-15; Table 14). Huntington et al. also teach that the reactive center loop (RCL) of the serpin family is highly conserved and can be mutated at any position to alter activity (please refer to the entire specification particularly paragraphs 30-38). Huntington et al. teach that P17-P3’ is the RCL for a1-antitrypsin (please refer to the entire specification particularly paragraph 38). Huntington et al. also teach that P1’ can be mutated to Q, N, Y, I, M, V, R, H, K, C, A, S, or E; P1 can also be mutated to K; and P2 can also be mutated to Q, N, Y, I, V, R, K, or T (please refer to the entire specification particularly paragraphs 38-63).
However, Huntington et al. do not teach modification of P3.
For present claims 1, 3-5, 8, and 17, Felber et al. teach mutated serpins wherein P3 is L (i.e. residue 2 of present SEQ ID NO: 28) and P2 is L and P1 is R (please refer to the entire reference particularly the abstract; Table 1).
All the claimed elements (i.e. mutation of the RCL of serpins; utilizing mutated serpins to treat various bleeding disorders) were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because the substitution of one known element (i.e. a1 antitrypsin/serpin with mutated RCL at residues P4, P2, P1, and/or P1’) for another (i.e. serpin with a P3 mutation) would have yielded predictable results (i.e. ability to treat bleeding disorders) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. mutation of P3 to leucine in the RCL of serpins) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because a person of ordinary skill has good reason to pursue the known options within their technical grasp. If this leads to the anticipated success, it is likely the product no of innovation but of ordinary skill and common sense. See KSR International Co v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 103 as being unpatentable over Huntington et al. and Felber et al. for claims 1, 3-5, 8, and 17 were considered but are not persuasive for the following reasons.
Applicants contend that since Huntington et al. teaches a1 antitrypsin and Felber et al. teaches ACT, that one of skill in the art would not combine the references.
Applicants’ arguments are not convincing since the teachings of Huntington et al. and Felber et al. render the method of the instant claims prima facie obvious.
Huntington et al. also teach that the reactive center loop (RCL) of the serpin family is highly conserved and can be mutated at any position to alter activity (please refer to the entire specification particularly paragraphs 30-38). Huntington et al. teach that P17-P3’ is the RCL for a1-antitrypsin (please refer to the entire specification particularly paragraph 38).
Claims 1, 3-5, 8, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Huntington et al. U.S. Patent Application Publication 2016/0311887 published October 27, 2016; Bock U.S. Patent Application Publication 2007/0259809 published November 8, 2007; and Kaplan et al., 2010, The plasma bradykinin-forming pathways and its relationship with complement, Molecular Immunology, 47: 2161-2169.
For present claims 1, 3-5, 8, and 17, Huntington et al. teach methods of administering modified a1 antitrypsin (residues 25-418 of SEQ ID NO: 7; present SEQ ID NO: 1) wherein P4 is S, P2 is L, and P1 is R (i.e. SXLR of present SEQ ID NO: 28) to a subject wherein the subject has a disease associated with hemostasis, bleeding, hemorrhage, bleeding disorders, trauma, deficiencies in clotting factors, etc. (please refer to the entire specification particularly the abstract; paragraphs 2, 8-30, 34-63, 67, 116-120, 124, 144, 151-161, 169, 170, 191, 196-219, 241, 227, 244, 245, 292, 294, 295; Figures 1-15; Table 14). Huntington et al. also teach that the reactive center loop (RCL) of the serpin family is highly conserved and can be mutated at any position to alter activity (please refer to the entire specification particularly paragraphs 30-38). Huntington et al. teach that P17-P3’ is the RCL for a1-antitrypsin (please refer to the entire specification particularly paragraph 38). Huntington et al. also teach that P1’ can be mutated to Q, N, Y, I, M, V, R, H, K, C, A, S, or E; P1 can also be mutated to K; and P2 can also be mutated to Q, N, Y, I, V, R, K, or T (please refer to the entire specification particularly paragraphs 38-63).
However, Huntington et al. do not teach modification of P3.
For present claims 1, 3-5, 8, and 17, Bock teaches methods of administering mutated serpins wherein P3 is L (i.e. residue 2 of present SEQ ID NO: 28) for treatment of bleeding disorders (please refer to the entire specification particularly the abstract; paragraphs 3, 5, 37, 38, 89, 90, 105, 108, 109, 112, 123, 125).
For present claims 1, 3-5, 8, and 17, Kaplan et al. teach the importance of clotting factors in angioedema and hereditary angioedema (HAE) (please refer to the entire reference particularly the abstract; Figures 2 and 3; sections 6.2, 6.3).
All the claimed elements (i.e. mutation of the RCL of serpins; utilizing mutated serpins to treat various bleeding disorders) were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because the substitution of one known element (i.e. a1 antitrypsin/serpin with mutated RCL at residues P4, P2, P1, and/or P1’) for another (i.e. serpin with a P3 mutation) would have yielded predictable results (i.e. ability to treat bleeding disorders) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. mutation of P3 to leucine in the RCL of serpins) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because a person of ordinary skill has good reason to pursue the known options within their technical grasp. If this leads to the anticipated success, it is likely the product no of innovation but of ordinary skill and common sense. See KSR International Co v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 103 as being unpatentable over Huntington et al., Bock, and Kaplan et al. for claims 1, 3-5, 8, and 17 were considered but are not persuasive for the following reasons.
Applicants contend that since Huntington et al. teaches a1 antitrypsin and Bock et al. teaches ATIII, that one of skill in the art would not combine the references.
Applicants’ arguments are not convincing since the teachings of Huntington et al., Bock, and Kaplan et al. render the method of the instant claims prima facie obvious.
Huntington et al. also teach that the reactive center loop (RCL) of the serpin family is highly conserved and can be mutated at any position to alter activity (please refer to the entire specification particularly paragraphs 30-38). Huntington et al. teach that P17-P3’ is the RCL for a1-antitrypsin (please refer to the entire specification particularly paragraph 38).
Claims 1, 3-5, 8, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Huntington et al. U.S. Patent Application Publication 2016/0311887 published October 27, 2016; Felber et al., 2006, Mutant recombinant serpins as highly specific inhibitors of human kallikrein, FEBS Journal, 273: 2505-2514; and Kaplan et al., 2010, The plasma bradykinin-forming pathways and its relationship with complement, Molecular Immunology, 47: 2161-2169.
For present claims 1, 3-5, 8, and 17, Huntington et al. teach methods of administering modified a1 antitrypsin (residues 25-418 of SEQ ID NO: 7; present SEQ ID NO: 1) wherein P4 is S, P2 is L, and P1 is R (i.e. SXLR of present SEQ ID NO: 28) to a subject wherein the subject has a disease associated with hemostasis, bleeding, hemorrhage, bleeding disorders, trauma, deficiencies in clotting factors, etc. (please refer to the entire specification particularly the abstract; paragraphs 2, 8-30, 34-63, 67, 116-120, 124, 144, 151-161, 169, 170, 191, 196-219, 241, 227, 244, 245, 292, 294, 295; Figures 1-15; Table 14). Huntington et al. also teach that the reactive center loop (RCL) of the serpin family is highly conserved and can be mutated at any position to alter activity (please refer to the entire specification particularly paragraphs 30-38). Huntington et al. teach that P17-P3’ is the RCL for a1-antitrypsin (please refer to the entire specification particularly paragraph 38). Huntington et al. also teach that P1’ can be mutated to Q, N, Y, I, M, V, R, H, K, C, A, S, or E; P1 can also be mutated to K; and P2 can also be mutated to Q, N, Y, I, V, R, K, or T (please refer to the entire specification particularly paragraphs 38-63).
However, Huntington et al. do not teach modification of P3.
For present claims 1, 3-5, 8, and 17, Felber et al. teach mutated serpins wherein P3 is L (i.e. residue 2 of present SEQ ID NO: 28) and P2 is L and P1 is R (please refer to the entire reference particularly the abstract; Table 1).
For present claims 1, 3-5, 8, and 17, Kaplan et al. teach the importance of clotting factors in angioedema and hereditary angioedema (HAE) (please refer to the entire reference particularly the abstract; Figures 2 and 3; sections 6.2, 6.3).
All the claimed elements (i.e. mutation of the RCL of serpins; utilizing mutated serpins to treat various bleeding disorders) were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because the substitution of one known element (i.e. a1 antitrypsin/serpin with mutated RCL at residues P4, P2, P1, and/or P1’) for another (i.e. serpin with a P3 mutation) would have yielded predictable results (i.e. ability to treat bleeding disorders) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. mutation of P3 to leucine in the RCL of serpins) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because a person of ordinary skill has good reason to pursue the known options within their technical grasp. If this leads to the anticipated success, it is likely the product no of innovation but of ordinary skill and common sense. See KSR International Co v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 103 as being unpatentable over Huntington et al., Felber et al., and Kaplan et al. for claims 1, 3-5, 8, and 17 were considered but are not persuasive for the following reasons.
Applicants contend that since Huntington et al. teaches a1 antitrypsin and Felber et al. teaches ACT, that one of skill in the art would not combine the references.
Applicants’ arguments are not convincing since the teachings of Huntington et al., Felber et al., and Kaplan et al. render the method of the instant claims prima facie obvious.
Huntington et al. also teach that the reactive center loop (RCL) of the serpin family is highly conserved and can be mutated at any position to alter activity (please refer to the entire specification particularly paragraphs 30-38). Huntington et al. teach that P17-P3’ is the RCL for a1-antitrypsin (please refer to the entire specification particularly paragraph 38).
The discovery of a mechanism of action is a discovery and not necessarily an invention.
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 1, 3-5, 8, and 17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11,851,474 in view of Huntington et al. U.S. Patent Application Publication 2016/0311887 published October 27, 2016 and Bock U.S. Patent Application Publication 2007/0259809 published November 8, 2007.
U.S. Patent No. 11,851,474 claims a method of treating a bradykinin-mediated disease via administering a modified a1 antitrypsin with a RCL of SEQ ID NOs: 12, 18, 23, 24, 25, and 27 wherein P4 is serine, P3 is leucine, and P1 is arginine and wherein the diseases are the same in present claim 8 and claim 12 of U.S. Patent No. 11,851,474.
Huntington et al. teach methods of administering modified a1 antitrypsin (residues 25-418 of SEQ ID NO: 7; present SEQ ID NO: 1) wherein P4 is S, P2 is L, and P1 is R (i.e. SXLR of present SEQ ID NO: 28) to a subject wherein the subject has a disease associated with hemostasis, bleeding, hemorrhage, bleeding disorders, trauma, deficiencies in clotting factors, etc. (please refer to the entire specification particularly the abstract; paragraphs 2, 8-30, 34-63, 67, 116-120, 124, 144, 151-161, 169, 170, 191, 196-219, 241, 227, 244, 245, 292, 294, 295; Figures 1-15; Table 14). Huntington et al. also teach that the reactive center loop (RCL) of the serpin family is highly conserved and can be mutated at any position to alter activity (please refer to the entire specification particularly paragraphs 30-38). Huntington et al. teach that P17-P3’ is the RCL for a1-antitrypsin (please refer to the entire specification particularly paragraph 38). Huntington et al. also teach that P1’ can be mutated to Q, N, Y, I, M, V, R, H, K, C, A, S, or E; P1 can also be mutated to K; and P2 can also be mutated to Q, N, Y, I, V, R, K, or T (please refer to the entire specification particularly paragraphs 38-63).
Bock teaches methods of administering mutated serpins wherein P3 is L (i.e. residue 2 of present SEQ ID NO: 28) for treatment of bleeding disorders (please refer to the entire specification particularly the abstract; paragraphs 3, 5, 37, 38, 89, 90, 105, 108, 109, 112, 123, 125).
All the claimed elements (i.e. mutation of the RCL of serpins; utilizing mutated serpins to treat various bleeding disorders) were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because the substitution of one known element (i.e. a1 antitrypsin/serpin with mutated RCL at residues P4, P2, P1, and/or P1’) for another (i.e. serpin with a P3 mutation) would have yielded predictable results (i.e. ability to treat bleeding disorders) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. mutation of P3 to leucine in the RCL of serpins) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because a person of ordinary skill has good reason to pursue the known options within their technical grasp. If this leads to the anticipated success, it is likely the product no of innovation but of ordinary skill and common sense. See KSR International Co v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over U.S. Patent No. 11,851,474 in view of Huntington et al. and Bock for claims 1, 3-5, 8, and 17 were considered but are not persuasive for the following reasons.
Applicants refer to the arguments for the 35 USC 103 rejection above.
Applicants’ arguments are not convincing since the claimed invention of U.S. Patent No. 11,851,474 in view of Huntington et al. and Bock renders obvious the method of the instant claims. In addition, while a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP § 714.02). Please refer to the above arguments regarding the 35 USC 103 rejection.
Claims 1, 3-5, 8, and 17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11,851,474 in view of Huntington et al. U.S. Patent Application Publication 2016/0311887 published October 27, 2016 and Felber et al., 2006, Mutant recombinant serpins as highly specific inhibitors of human kallikrein, FEBS Journal, 273: 2505-2514.
U.S. Patent No. 11,851,474 claims a method of treating a bradykinin-mediated disease via administering a modified a1 antitrypsin with a RCL of SEQ ID NOs: 12, 18, 23, 24, 25, and 27 wherein P4 is serine, P3 is leucine, and P1 is arginine and wherein the diseases are the same in present claim 8 and claim 12 of U.S. Patent No. 11,851,474.
Huntington et al. teach methods of administering modified a1 antitrypsin (residues 25-418 of SEQ ID NO: 7; present SEQ ID NO: 1) wherein P4 is S, P2 is L, and P1 is R (i.e. SXLR of present SEQ ID NO: 28) to a subject wherein the subject has a disease associated with hemostasis, bleeding, hemorrhage, bleeding disorders, trauma, deficiencies in clotting factors, etc. (please refer to the entire specification particularly the abstract; paragraphs 2, 8-30, 34-63, 67, 116-120, 124, 144, 151-161, 169, 170, 191, 196-219, 241, 227, 244, 245, 292, 294, 295; Figures 1-15; Table 14). Huntington et al. also teach that the reactive center loop (RCL) of the serpin family is highly conserved and can be mutated at any position to alter activity (please refer to the entire specification particularly paragraphs 30-38). Huntington et al. teach that P17-P3’ is the RCL for a1-antitrypsin (please refer to the entire specification particularly paragraph 38). Huntington et al. also teach that P1’ can be mutated to Q, N, Y, I, M, V, R, H, K, C, A, S, or E; P1 can also be mutated to K; and P2 can also be mutated to Q, N, Y, I, V, R, K, or T (please refer to the entire specification particularly paragraphs 38-63).
Felber et al. teach mutated serpin wherein P3 is L (i.e. residue 2 of present SEQ ID NO: 28) and P2 is L and P1 is R (please refer to the entire reference particularly the abstract; Table 1).
All the claimed elements (i.e. mutation of the RCL of serpins; utilizing mutated serpins to treat various bleeding disorders) were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because the substitution of one known element (i.e. a1 antitrypsin/serpin with mutated RCL at residues P4, P2, P1, and/or P1’) for another (i.e. serpin with a P3 mutation) would have yielded predictable results (i.e. ability to treat bleeding disorders) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. mutation of P3 to leucine in the RCL of serpins) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because a person of ordinary skill has good reason to pursue the known options within their technical grasp. If this leads to the anticipated success, it is likely the product no of innovation but of ordinary skill and common sense. See KSR International Co v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over U.S. Patent No. 11,851,474 in view of Huntington et al. and Felber et al. for claims 1, 3-5, and 8 were considered but are not persuasive for the following reasons.
Applicants refer to the arguments for the 35 USC 103 rejection above.
Applicants’ arguments are not convincing since the claimed invention of U.S. Patent No. 11,851,474 in view of Huntington et al. and Felber et al. renders obvious the method of the instant claims. In addition, while a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP § 714.02). Please refer to the above arguments regarding the 35 USC 103 rejection.
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/AMBER D STEELE/Primary Examiner, Art Unit 1658
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