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 .
Election/Restrictions and Claim Status
Applicant’s election without traverse of Group 1 and the species of fusion protein of SEQ ID NO:16 (with mutation at R273 and ectodomain SEQ ID NO:6) in the reply filed on 10/1/25 is acknowledged.
Claims to the elected group are rejected as set forth below. Any relevant art that was uncovered during the search for the elected species is cited herein in order to advance prosecution.
Claims 27, 29-30, 33 and 35-36 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/1/25.
The elected fusion protein (SEQ ID NO:16) does not include a linking sequence as in claim 25.
Claim 25 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/1/25.
Claims 3, 5-13, 16, 22, 28, 31-32, 34 and 37 have been canceled.
Claims 1-2, 4, 14-15, 17-21, 23-24 and 26 are being examined.
Priority
The priority information is found in the filing receipt dated 6/4/24.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 1/5/24 (8 pages) and 1/5/24 (6 pages) have been considered by the examiner.
Specification
The disclosure is objected to because of the following informalities:
Section 00113 of the specification refers to supplementary figure S2. However, there are no supplementary figures.
Section 00120 of the specification refers to supplementary figure S1 and supplementary figure S2. However, there are no supplementary figures.
37 CFR 1.821(d) recognizes that each occurrence of a sequence is to include the corresponding sequence identifier and if a sequence is present in the drawing the sequence identifier can be in the drawing or the brief description of the drawing.
In the instant case, figures 6-8 recite sequences but do not include the corresponding sequence identifier in either the drawing or description (see sections 0009-0011). Section 0005 of the specification recites sequences but does not include the corresponding sequence identifier.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2, 4, 21 and 24 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.
Claims 2 and 4 refer to particular residue positions but do not recite a corresponding sequence as a point of reference. Applicants own specification recognizes that the ACE2 protein has a leader sequence and the numbering is different if the leader sequence is included (section 0034).
Claim 21 refers to a constant region of SEQ ID NO:14 and claim 24 recites fusions that comprise SEQ ID NO:14. The instant specification describes the Fc as being described previously (section 00109) and as being human and from the constant region (section 0075). Instant SEQ ID NO:14 and the sequences of claim 24 include 2 consecutive repeats of the sequence NWYVDGVEVHNAKTKPRE (beginning at residue 64 of SEQ ID NO:14). SEQ ID NO:14 is listed as a human sequence in the sequence listing. NCBI entry for IgG chain C (retrieved from https://www.ncbi.nlm.nih.gov/protein/4CDH_A?report=genbank&log$=protalign&blast_rank=3&RID=M04BA17R014 on 12/15/25, 3 pages) reveals that the human sequence includes one occurrence of the sequence NWYVDGVEVHNAKTKPRE (beginning at residue 84 on page 3), not two. There does not appear to be any human sequence that is identical to SEQ ID NO:14. In the instant case, certain sequences are described in one manner but do not correspond to how they are described. As such, the scope of the claims is unclear. Although applicant can act as their own lexicographer (see MPEP 2111.01 IV) in such situations an explicit definition is to be provided.
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 1-2, 4, 14-15, 17-21, 23 and 26 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.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated:
“To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the invention, with all its claimed limitations, not that which makes it obvious,” and by using “such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient.” MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
Further, to provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include: a) the scope of the invention; b) actual reduction to practice; c) disclosure of drawings or structural chemical formulas; d) relevant identifying characteristics including complete structure, partial structure, physical and/or chemical properties, and structure/function correlation; e) method of making the claimed compounds; f) level of skill and knowledge in the art; and g) predictability in the art.
(1) Scope of the invention/Partial structure/disclosure of drawings:
Claim 1 recites ‘one or more mutations in ACE2’ and refers to functional properties including binding and reduced peptidase activity. The instant specification recognizes ACE2 as being SEQ ID NO:1 which is 805 amino acids in length. One or more mutations could be 20, 50, 100, 200, 400, 600 or 700 mutations for example. In addition to the location of the mutation, any given position can be modified to at least any of the 20 standard amino acids, Thus, claim 2 for example encompasses many possible mutations. In addition claim 1 recites ‘at least a portion of the ectodomain’ and ‘at least a portion of the constant region’. Such phrases are broad and encompass many possibilities. Although certain claims further describe either the ectodomain or the constant region, only claim 24 (not included in the instant rejection) further describes both. When 20 of the positions are varied to any of the 20 common amino acids there are at least 2020 (i.e. 104857600000000000000000000) different possible sequences. As such, the genus is large.
The examples (figures 2-4 for example) relate to a limited number of specific ectodomain mutations (and very few combinations of mutations) and very few portions of constant regions.
(2) Level of skill and knowledge in the art/predictability in the art:
The level of skill in the art is high.
Claim 1 recites ‘one or more mutations in ACE2’ and refers to functional properties including binding and reduced peptidase activity.
With respect to reduced peptidase activity, applicants own specification states that numerous mutations remain active toward AngII and apelin-13 (section 00121) Sheet 5 of the drawings shows that at least 2 of the mutations do not appear to reduce Mca-APK. Sheet 7 of the drawings shows that at least 3 of the mutations do not appear to reduce AngII. Applicants own specification refers to unique steric conformations and that individual ACE2 residues display distinct results (section 00121).
(3) Physical and/or chemical properties and (4) Functional characteristics:
Claim 1 recites ‘one or more mutations in ACE2’ and refers to functional properties including binding and reduced peptidase activity. The instant specification mentions carboxypeptidase, endopeptidase and metallocarboxypeptidase activity (section 0042). With respect to reduced peptidase activity, applicants own specification states that numerous mutations remain active toward AngII and apelin-13 (section 00121) Sheet 5 of the drawings shows that at least 2 of the mutations do not appear to reduce Mca-APK. Sheet 7 of the drawings shows that at least 3 of the mutations do not appear to reduce AngII. Applicants own specification refers to unique steric conformations and that individual ACE2 residues display distinct results (section 00121). Due to the unique behavior one would not necessarily extrapolate from one mutation to another.
There is no adequate disclosed correlation between structure and function particularly related to what structures are adequate to result in the functions as recited in the claims specifically for the many possible mutations and combination of mutations and portions. When 20 of the positions are varied to any of the 20 common amino acids there are at least 2020 (i.e. 104857600000000000000000000) different possible sequences. One of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus and that there is a lack of the predictability in the art thus that the applicant was not in possession of the claimed genus.
(5) Method of making the claimed invention/actual reduction to practice:
The specification (example 1 pages 22-23) describes making fusions. However, mere synthesis of a fusion does not show that it would have the functionalities claimed.
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”) Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Claim Rejections - 35 USC § 102
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 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.
Claim(s) 1-2, 14-15, 17, 19-21, 23 and 26 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lei et al. (NPL cite 5 of 6 page IDS of 1/5/24; ‘Lei’).
The 2nd page of Lei (3rd and 4th paragraphs) refers to supplementary data. For completeness of the record a copy of the supplemental data (Supplemental Data for Lei et al. ‘Neutralization of SARS-CoV-2 spike pseudotyped virus by recombinant ACE2-Ig’ Nat Commun April 2020, 5 pages; ‘LeiSupplement’) is provided.
The 4th page of Lei et al. states that the article was published 24 April 2020.
Lei teach a recombinant protein connecting the extracellular domain of human ACE2 and the Fc region of the human IgG1 specifically an ACE2 mutant with low catalytic activity (abstract). Lei teach that mACE2-Ig is a fusion that includes H374N and H378N (page 2 paragraph connecting columns 1-2, figure 1 and supplementary Table 1). Lei teach that the mACE2-Ig fusion was expressed and purified and assayed (page 2 paragraph connecting columns 1-2). Lei teach the fusion protein has high binding affinity for SARS-CoV-2 (abstract).
In relation to the fusion protein of claim 1, Lei teach a recombinant protein connecting the extracellular domain of human ACE2 and the Fc region of the human IgG1 specifically an ACE2 mutant with low catalytic activity (abstract). Lei teach the fusion protein has high binding affinity for SARS-CoV-2 (abstract). Lei teach that mACE2-Ig is a fusion that includes H374N and H378N (page 2 paragraph connecting columns 1-2, figure 1 and supplementary Table 1).
In relation to the one or more mutations of claims 1-2 and 14-15, Lei teach that mACE2-Ig is a fusion that includes H374N and H378N (page 2 paragraph connecting columns 1-2, figure 1 and supplementary Table 1). Lei teach low catalytic activity with the mutant (abstract).
In relation to the ectodomain of claims 14-15 and 17, LeiSupplement (supplementary Table 1) shows STI… (in the first line of the sequence of mACE2-Ig) corresponding to S19-I21 as well as …PVS (6th to last line of the sequence of mACE2-Ig) corresponding to P738-S740 (with no I after the PVS so excluding 741-805).
In relation to the constant region of claims 1, 19-21 and 23, Lei teach the Fc region of the human IgG1 (abstract) and figure 1 shows a disulfide bond and a homodimer. LeiSupplement (supplementary Table 1) shows the sequence (last 6 lines in table 1). Although unclear (see 112 rejection above), the claim limitations have been interpreted as being met. The instant specification describes the Fc as being described previously (section 00109) and as being human and from the constant region (section 0075).
In relation to claim 26, Lei teach that the mACE2-Ig fusion was expressed and purified and assayed (page 2 paragraph connecting columns 1-2).
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-2, 4, 14-15, 17-21, 23-24 and 26 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Kolls et al. (WO 2021/217120, 10-2021; ‘Kolls’).
Kolls teach fusion proteins with mutated forms of the extracellular domain of ACE2 for binding SARS-CoV-2 (abstract). Kolls teach the human soluble ACE2 ectodomain (figure 10 SEQ ID NO:1). Kolls teach MDR503-Fc which corresponds to the R273A mutation to inactivate catalysis (section 0044). Kolls teach generation of the constructs specifically with IgG1 (section 0092). Kolls teach that the fusion protein was assayed (figure 2 and figure 2 caption).
In relation to the fusion protein of claim 1, Kolls teach fusion proteins with mutated forms of the extracellular domain of ACE2 for binding SARS-CoV-2 (abstract). Kolls teach the human soluble ACE2 ectodomain (figure 10 SEQ ID NO:1). Kolls teach MDR503-Fc which corresponds to the R273A mutation to inactivate catalysis (section 0044).
In relation to the one or more mutations of claims 1-2, 4, 14-15 and 18, Kolls teach the human soluble ACE2 ectodomain (figure 10 SEQ ID NO:1). Kolls teach MDR503-Fc which corresponds to the R273A mutation to inactivate catalysis (section 0044) which comprises instant SEQ ID NO:6.
In relation to the ectodomain of claims 14-15 and 17, Kolls teach the human soluble ACE2 ectodomain (figure 10) which comprises STI… (in the first line) corresponding to S19-I21 as well as …PVS (last line of the sequence) corresponding to P738-S740 (with no I after the PVS so excluding 741-805).
In relation to the constant region of claims 1, 19-21 and 23-24, Kolls teach MDR503-Fc which corresponds to the R273A mutation to inactivate catalysis (section 0044). Kolls teach generation of the constructs specifically with IgG1 (section 0092) and shows a homodimer (figure 1). Although unclear (see 112 rejection above), the claim limitations have been interpreted as being met. The instant specification describes the Fc as being described previously (section 00109) and as being human and from the constant region (section 0075).
In relation to claim 26, Kolls teach that the fusion protein was assayed (figure 2 and figure 2 caption).
Kolls claims priority to 63/014,77 which recites in table 2 the sequence for hACE2 ED R273A Ig.
Claim Rejections - 35 USC § 103
Due to the lack of clarity of the claims, the rejections below address additional embodiments of the claims.
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) 1-2, 4, 14-15, 17-21, 23-24 and 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lei et al. (NPL cite 5 of 6 page IDS of 1/5/24; ‘Lei’) in view of Kolls et al. (WO 2021/217120, 10-2021; ‘Kolls’).
The 2nd page of Lei (3rd and 4th paragraphs) refers to supplementary data. For completeness of the record a copy of the supplemental data (Supplemental Data for Lei et al. ‘Neutralization of SARS-CoV-2 spike pseudotyped virus by recombinant ACE2-Ig’ Nat Commun April 2020, 5 pages; ‘LeiSupplement’) is included.
The 4th page of Lei et al. states that the article was published 24 April 2020.
Lei teach a recombinant protein connecting the extracellular domain of human ACE2 and the Fc region of the human IgG1 specifically an ACE2 mutant with low catalytic activity (abstract) and specifically recite mutations to ‘reduce the catalytic activity’ (page 2 paragraph connecting columns 1-2). Lei teach that the mACE2-Ig fusion was expressed and purified and assayed (page 2 paragraph connecting columns 1-2). Lei teach the fusion protein has high binding affinity for SARS-CoV-2 (abstract).
Lei does not teach the R273A mutation.
Kolls teach fusion proteins with mutated forms of the extracellular domain of ACE2 for binding SARS-CoV-2 (abstract). Kolls teach the human soluble ACE2 ectodomain (figure 10). Kolls teach MDR503-Fc which corresponds to the R273A mutation to inactivate catalysis (section 0044).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of Lei because Lei teach an ACE2 mutant with low catalytic activity (abstract) and specifically recite mutations to ‘reduce the catalytic activity’ (page 2 paragraph connecting columns 1-2). Since Kolls teach the R273A mutation to inactivate catalysis (section 0044) one would have been motivated to make such mutant in the construct of Lei (i.e. substitute the ACE2 mutation of Kolls for the ACE2 mutant of Lei). One would have had a reasonable expectation of success since the methods of making mutations and protein production were known (see page 3518 of Guy). Further, Kolls teach MDR503-Fc which corresponds to the R273A mutation to inactivate catalysis (section 0044).
In relation to the fusion protein of claim 1, Lei teach a recombinant protein connecting the extracellular domain of human ACE2 and the Fc region of the human IgG1 specifically an ACE2 mutant with low catalytic activity (abstract). Lei teach the fusion protein has high binding affinity for SARS-CoV-2 (abstract). Kolls teach MDR503-Fc which corresponds to the R273A mutation to inactivate catalysis (section 0044).
In relation to the one or more mutations of claims 1-2, 14-15, 18 and 24, Kolls teach MDR503-Fc which corresponds to the R273A mutation to inactivate catalysis (section 0044).
In relation to the ectodomain of claims 14-15 and 17, LeiSupplement (supplementary Table 1) shows STI… (in the first line of the sequence of mACE2-Ig) corresponding to S19-I21 as well as …PVS (6th to last line of the sequence of mACE2-Ig) corresponding to P738-S740 (with no I after the PVS so excluding 741-805). Kolls teach the human soluble ACE2 ectodomain (figure 10) which comprises STI… (in the first line) corresponding to S19-I21 as well as …PVS (last line of the sequence) corresponding to P738-S740 (with no I after the PVS so excluding 741-805).
In relation to the constant region of claims 1, 19-21 and 23, Lei teach the Fc region of the human IgG1 (abstract) and figure 1 shows a disulfide bond. LeiSupplement (supplementary Table 1) shows the sequence (last 6 lines in table 1). Although unclear (see 112 rejection above), the claim limitations have been interpreted as being met. The instant specification describes the Fc as being described previously (section 00109) and as being human and from the constant region (section 0075). Further, Kolls recognizes various embodiments of the Fc (pages 5-6 connecting paragraph).
In relation to claim 26, Lei teach that the mACE2-Ig fusion was expressed and purified and assayed (page 2 paragraph connecting columns 1-2).
Kolls claims priority to 63/014,77 which recites in table 2 the sequence for hACE2 ED R273A Ig.
Claim(s) 1-2, 4, 14-15, 17-21, 23-24 and 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lei et al. (NPL cite 5 of 6 page IDS of 1/5/24; ‘Lei’) in view of Guy et al. (NPL citation 8 of 6 page IDS of 1/5/24; ‘Guy’).
The 2nd page of Lei (3rd and 4th paragraphs) refers to supplementary data. For completeness of the record a copy of the supplemental data (Supplemental Data for Lei et al. ‘Neutralization of SARS-CoV-2 spike pseudotyped virus by recombinant ACE2-Ig’ Nat Commun April 2020, 5 pages; ‘LeiSupplement’) is provided.
The 4th page of Lei et al. states that the article was published 24 April 2020.
Lei teach a recombinant protein connecting the extracellular domain of human ACE2 and the Fc region of the human IgG1 specifically an ACE2 mutant with low catalytic activity (abstract) and specifically recite mutations to ‘reduce the catalytic activity’ (page 2 paragraph connecting columns 1-2). Lei teach that the mACE2-Ig fusion was expressed and purified and assayed (page 2 paragraph connecting columns 1-2). Lei teach the fusion protein has high binding affinity for SARS-CoV-2 (abstract).
Lei does not teach the R273A mutation.
Guy teach ACE2 and teach that replacement of Arg273 causes enzyme activity to be abolished (abstract). Guy recognizes replacement of a residue with alanine (page 3514 first paragraph). Guy teach that site directed mutagenesis was performed and the protein was expressed (page 3518).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of Lei because Lei teach an ACE2 mutant with low catalytic activity (abstract) and specifically recite mutations to ‘reduce the catalytic activity’ (page 2 paragraph connecting columns 1-2). Since Guy teach ACE2 and teach that replacement of Arg273 causes enzyme activity to be abolished (abstract) one would have been motivated to mutate as suggested by Guy (Arg273Ala) (i.e. substitute the ACE2 mutation of Guy for the ACE2 mutant of Lei). One would have had a reasonable expectation of success since the methods of making mutations and protein production were known (page 2 paragraph connecting columns 1-2 of Lei). Further, Guy teach ACE2 and teach that replacement of Arg273 causes enzyme activity to be abolished (abstract).
In relation to the fusion protein of claim 1, Lei teach a recombinant protein connecting the extracellular domain of human ACE2 and the Fc region of the human IgG1 specifically an ACE2 mutant with low catalytic activity (abstract). Guy teach ACE2 and teach that replacement of Arg273 causes enzyme activity to be abolished (abstract).
In relation to the one or more mutations of claims 1-2, 14-15, 18 and 24, Guy teach ACE2 and teach that replacement of Arg273 causes enzyme activity to be abolished (abstract). Guy recognizes replacement of a residue with alanine (page 3514 first paragraph).
In relation to the ectodomain of claims 14-15 and 17, LeiSupplement (supplementary Table 1) shows STI… (in the first line of the sequence of mACE2-Ig) corresponding to S19-I21 as well as …PVS (6th to last line of the sequence of mACE2-Ig) corresponding to P738-S740 (with no I after the PVS so excluding 741-805).
In relation to the constant region of claims 1, 19-21 and 23, Lei teach the Fc region of the human IgG1 (abstract) and figure 1 shows a disulfide bond. LeiSupplement (supplementary Table 1) shows the sequence (last 6 lines in table 1). Although unclear (see 112 rejection above), the claim limitations have been interpreted as being met. The instant specification describes the Fc as being described previously (section 00109) and as being human and from the constant region (section 0075).
In relation to claim 26, Lei teach that the mACE2-Ig fusion was expressed and purified and assayed (page 2 paragraph connecting columns 1-2).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RONALD T NIEBAUER whose telephone number is (571)270-3059. The examiner can normally be reached M - F 6:30 - 2:30 EST.
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RONALD T. NIEBAUER
Primary Examiner
Art Unit 1658
/RONALD T NIEBAUER/Examiner, Art Unit 1658