DETAILED ACTION
Status of Application, Amendments and/or Claims
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The amendment of 9/11/25 has been entered in full. Claims 3, 5-9, 11-15, 18, 22-23, 26, 28-31 and 33-36 are amended. Claims 1-37 are pending.
Election/Restrictions
In view of the amendments, claims 5-23 and 30-37 are no longer improper multiple dependent claims. As such, claims 5-17 are now placed in inventive Group I, claims 18-23 in Group II, claims 30-36 in Group III, and claim 37 in Group IV. See the restriction requirement mailed 6/2/25.
Applicants' election without traverse of Group I, currently claims 1-17 and 24, in the reply filed on 9/11/25 is acknowledged. Claims 18-23 and 25-37 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-17 and 24 are under consideration.
Specification
The disclosure is objected to for the following informalities:
---The title is not descriptive because it is directed generally to any binding protein useful against ACE2 targeted viruses, whereas the claims are limited to a binding protein comprising an extracellular portion of ACE2, a linker and an Fc domain A new title is required that is clearly indicative of the invention to which the claims are directed. The following title is suggested: “Binding Protein Comprising an Extracellular Portion of ACE2, Linker and Fc Domain Useful Against ACE2-Targeted Viruses”.
---The disclosure is objected to because it contains an embedded hyperlink (browser-executable code) in ¶ 97 on page 23; this hyperlink should be removed; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01 (VII).
---The specification at ¶ 135 twice indicates that SEQ ID NO: 4 is an example of a sequence comprising two substitution mutations, H374N and H378N. However, the specification at page 71 identifies SEQ ID NO: 4 as a “Hinge+Fc” sequence that does not contain any ACE2 sequences, and therefore does not contain the H374N and H378N mutations that are made the ACE2 ECD.
---The specification at ¶ 139 states that Figure 15 “shows an annotated sequence listing of wild type human ACE2. This sequence shows the collectrin domain, amino acids 615-740 (boxed)”. However, the box in Figure 15 is shown around residues 626-740. Therefore, the text of ¶ 139 does not match what is shown in the Figure.
---The sequence rules (37 CFR 1.821-1.825) “embrace all unbranched nucleotide sequences with ten or more nucleotide bases and all unbranched, non-D amino acid sequences with four or more amino acids, provide that there are at least 10 “specifically defined” nucleotides or 4 “specifically defined” amino acids” (MPEP 2421.02). The specification, filed on 9/23/22, contains the following amino acid and nucleic acid sequences that are not accompanied by the required sequence identifier (SEQ ID NO), indicating that the sequence has been included in the sequence listing:
GGGGS (¶ 8, 9, 12, 21, 29, 33, 47, 92, 146, 222, 224, 231; claim 11; Figures 1B, 2B, 6C, 7D); EAAAK (¶ 8, 47); the full-length ACE2 amino acid sequence shown in Figure 15; GGGS (¶ 21); KESGSVSSEQLAQFRSLD (¶ 186); EGKSSGSGSESKST (¶ 186); and GSAGSAAGSGEF (¶ 186).
If these sequences are in the current listing, or are part of a longer sequence found in the current listing, the specification can be placed in compliance with the sequence rules by amending the specification where each sequence occurs to identify each sequence by the appropriate sequence identifier (SEQ ID NO) or the appropriate residues of a longer SEQ ID NO. Alternately, if one or more of these sequences is not in the current sequence listing, Applicants must first update it to add the missing sequence(s), and then add the sequence identifier(s) to the specification. Note that sequences in Drawings can be placed in compliance by identifying the sequence by SEQ ID NO in either the drawing or in brief description of it in the specification.
Appropriate correction is required.
Duplicate Claims, Warning
Applicants are advised that should claim 13 be found allowable, claim 14 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Specifically, claim 14 repeats claim 13, but with the additional recitation that the G0 glycosylation patten comprises a biantennary core glycan structure of Manα1-6(Manα1-3)Manβ1-4GlcNAcβ1-4GlcNAcβ1 with terminal N-acetylglucosamine (N-GlcNAc) on each branch that enhances the trapping potency of the binding protein in mucus. The additional “biantennary core glycan structure of Manα1-6(Manα1-3)Manβ1-4GlcNAcβ1-4GlcNAcβ1 with terminal N-acetylglucosamine on each branch” simply states the art-recognized definition of a “G0 glycosylation pattern”. See Figures 4 and 5 of Raju et al (2003. BioProcess International. 44-53). Furthermore, the additional recitation that the N-GlcNAcs enhance the trapping potency in mucus is simply a statement of an inherent property of the binding protein comprising an oligosaccharide having a G0 glycosylation pattern; i.e., having a G0 glycosylation pattern by definition means that there will terminal N-GlcNAcs which means there will inherently be an enhancement of the trapping potency.
Claim Objections
Claims 8, 11 and 16 are objected to because of the following informalities:
In claim 8, lines 2-3, “up to 10 amino acid difference” should be “up to 10 amino acid differences”.
In claim 11, the amino acid sequence GGGGS is missing a sequence identifier.
In claim 16, line 1, “said excipient, or carrier” should be “said excipient or carrier”.
The remaining claim(s) are objected to for depending from an objected claim.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-17 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 pre-AIA the applicant regards as the invention.
In each of independent claims 1 and 24, the phrase “excluding the collectrin domain” is indefinite because the definitions of this domain in the specification are conflicting and thus render it unclear what amino acid residues of ACE2 are excluded from the claims. The specification at ¶ 134 (page 34) states that Figure 15 “shows an annotated sequence listing of wild type human ACE2. This sequence shows the collectrin domain, amino acids 615-740 (boxed)”. However, the box in Figure 15 is shown around residues 626-740. ¶ 134 further teaches SEQ ID NO: 11 as an example of the ACE2 ECD of the invention, but SEQ ID NO: 11 is a sequence of 597 amino acids that the specification teaches is “aa 19-615, excludes collectrin domain” (page 73). Elsewhere, however, the ACE2 ECD without the collectrin domain is taught as residues 18-614 (¶ 20, 217, 219). Thus, it is unclear whether “the collectrin domain” is defined as residues 615-740, 616-740 or 626-740, and this renders the claims indefinite as to what amino acid residues are excluded. Furthermore, if residues 615-740 are excluded, it is unclear how the sequence of SEQ ID NO: 11 can be encompassed as it includes residue 615.
Claim 2 recites the limitation “the dimers” in line 2. There is insufficient antecedent basis for this limitation in the claim. Specifically, parent claim 1 only refers to a single binding protein that functions to dimerize, and does not refer to a dimer per se. As such, parent claim 1 fails to provide antecedent basis for this limitation in the dependent claim.
Claim 16 recites the limitation “said excipient, or carrier” in lines 1. There is insufficient antecedent basis for this limitation in the claim. Specifically, parent claim 15 refers only to an excipient, and thus fails to provide antecedent basis for the alternative “said … carrier” recited in dependent claim 16.
Claim 24 is rejected for the same reason as claim 2 with respect to the recitation of “the dimers” in line 13.
The remaining claim(s) included in the rejection are dependent claims that depend from one of the claims rejected above, and encompass the same indefinite subject matter.
Claim Rejections - 35 USC § 112(d)
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 35 U.S.C. 112 (pre-AIA ), fourth paragraph:
Subject to the [fifth paragraph of 35 U.S.C. 112 (pre-AIA )], 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.
Claim 16 is 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.
Per MPEP 608.01(n).III, “If the dependent claim does not comply with the requirements of 35 U.S.C. 112(d), the examiner should reject the dependent claim under 35 U.S.C. 112(d) rather than objecting to the claim” and “a dependent claim must be rejected under 35 U.S.C. 112(d) if it omits an element from the claim upon which it depends or it fails to add a limitation to the claim upon which it depends”.
Specifically, claim 16 is directed to the pharmaceutical composition of claim 15, wherein said excipient, or carrier is configured for inhalation. However, parent claim 15 is directed to a pharmaceutical composition comprising a binding protein of claim 1 and a pharmaceutically acceptable excipient. Thus, claim 15 only recites an excipient, and does not recite a carrier. As such, claim 16 fails to narrow parent claim 15 because it recites an element not present in the parent claim. Therefore, dependent claim 16 is of improper dependent form because it fails to further limit the subject matter of parent claim 15.
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.
Claim Rejections - 35 USC § 112(a), written description
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 1-17 and 24 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112(a), it is necessary to understand what Applicants are claiming and what Applicants have possession of.
The claims are product claims that are directed to an isolated binding protein (BP) that binds to ACE2-targeted viruses, having an amino acid sequence comprising Formula I, which is A-(B)n-C, wherein A is an extracellular domain (ECD) of angiotensin-converting enzyme 2 (ACE2) excluding the collectrin domain; B is a polypeptide flexible linker; n is from 1 to 25; and C is an Fc domain; and wherein the BP dimerizes.
The ACE2 ECD provide the ability to binds to viruses, and thus is the active portion of the binding protein. The specification teaches that the full-length extracellular domain extends to residue 740 (¶ 35). The phrase “excluding the collectrin domain” is indefinite for the reasons set forth in the section “Claim Rejections – 35 U.S.C. 112(b)”, but is interpreted as reading on residues 615-740, 616-740 or 626-740. The specification does not provide a limiting definition of the term “extracellular portion”, instead only providing examples of such, such as fragments as small as 10 amino acids in length (¶ 150). As such, the claims encompass any “extracellular portion” that is any fragment of an ACE2 ECD of residues 1-625 that is two or more amino acids in length. The claims also encompass any “variant thereof”, and the term “variant” is also not provided with a limiting definition, and therefore encompasses ACE2-derived sequences with one or more mutations, without limit. Furthermore, the term “angiotensin-converting enzyme (ACE2)” is also not defined in the specification and thus itself broadly encompasses such variants, in addition to the term “variants” expressly recited in the claims. Dependent claim 7 limits the ACE2 ECD to one that has 80% or great identity with SEQ ID NO: 11; however, as this reference sequence has 597 amino acid this means that the claim still encompasses variants with up to 119 amino acid changes in combination throughout. Dependent claim 8 limits the ACE2 ECD to one having a sequence with up to 10 amino acid differences with respect to SEQ ID NO: 11. Dependent claims 9 and 10 limits the ACE2 ECD to one have “at least one mutation” (claim 9) that is “two or more mutations” (claim 1), which are each ranges without an upper limit. Thus, the claims are directed to a genus of variant ACE2 protein structures defined by function (binding to viruses). However, this definition by function is not alone sufficient to define the genus because it is only an indication of what the polypeptide does, rather than what it is. It is only a definition of a useful result rather than a definition of what achieves that result.
The prior art appreciates that "Mutations … are generally destabilizing, and can reduce protein … fitness" and "In general, more comprehensive understanding of how mutations affect protein fitness within living cells is needed, including their combined effects on function, thermodynamic and kinetic stability, and clearance through aggregation and degradation" (pg 602 of Tokuriki et al, 2009, Current Opinion in Structural Biology. 19: 596-604). Thus, knowledge of the amino acid sequence of the ECD of ACE2 alone is not sufficient for the skilled artisan at the time of the effective filing date to predict which mutations (substitutions, additions and deletions) will result in a truncated ECD that retains functionality.
The specification does not teach a minimal length for the ECD to retain the required functionality; i.e., the ability to bind to a coronavirus. Instead, the working examples only employ a fragment of SEQ ID NO: 11 (amino acids 19-615 of full-length human ACE2). With respect to mutations in the ECD of ACE2 that can be made and still retain the ability to bind to viruses, the working examples employ a variant of SEQ ID NO: 11 with mutations at positions 374 and 378 (SEQ ID NO: 2) that remove enzymatic activity but allow the protein to retain the ability to bind coronavirus. Figures 16A-B further provide a list of mutations, mostly single point, that have been identified elsewhere in a screen for their effect on ACE2 functionality (¶ 223). The mutations which increase interaction of the ACE2 ECD with viruses are found in the first 400 amino acids of the protein, but there are limited to single point mutations and thus do not correspond in scope to that which is claimed, which is a genus encompassing many multiples of mutations.
Thus, the limited examples of fragments and variants of the ACE2 ECD provided by the specification fail to correspond to the scope of the genus encompassed by the claims. The specification fails to describe the scope of amino acid changes can be made to the ACE2 ECD and still retain the ability to bind to a coronavirus. As such, the specification fails to disclose relevant identifying characteristics sufficient to describe the claimed invention in such full, clear, concise, and exact terms that a skilled artisan would recognize applicant was in possession of the claimed invention.
MPEP 2163 provides guidance for complying with the written description requirement of 35 U.S.C. 112(a) that the “specification shall contain a written description of the invention…”; this requirement is separate and distinct from the enablement requirement (Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1355 (Fed. Cir. 2010)). Written description for a claimed genus may be satisfied through sufficient description of a relevant number of species. This is dependent on whether one of skill in the art would recognize necessary common attributes or features possessed by the members of the genus. Generally, in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. Written description for a claimed genus can also be satisfied when relevant identifying characteristics are disclosed. Per MPEP 2163, “[d]etermine whether the specification discloses other relevant identifying characteristics sufficient to describe the claimed invention in such full, clear, concise, and exact terms that a skilled artisan would recognize applicant was in possession of the claimed invention. For example, if the art has established a strong correlation between structure and function, one skilled in the art would be able to predict with a reasonable degree of confidence the structure of the claimed invention from a recitation of its function. Thus, the written description requirement may be satisfied through disclosure of function and minimal structure when there is a well-established correlation between structure and function.” However, claiming by function does not necessarily satisfy the written description requirement. “[A] generic statement such as "vertebrate insulin cDNA" or "mammalian insulin cDNA," without more, is not an adequate written description of the genus because it does not distinguish the claimed genus from others, except by function. It does not specifically define any of the genes that fall within its definition. It does not define any structural features commonly possessed by members of the genus that distinguish them from others … A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is. It is only a definition of a useful result rather than a definition of what achieves that result” (Regents of the University of California v. Eli Lilly Co., 119 F.3d 1559 (Fed. Cir. 1997)). Also, “[w]hen a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus" (Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005)), and “[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can 'visualize or recognize' the members of the genus” (AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69).
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111 (Fed. Cir. 1991), clearly states “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” (pg 1117). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed” (pg 1116). As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of fragments and variants of the ACE2 ECD and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016 (Fed. Cir. 1991). One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483 (BPAI 1993). In Fiddes, claims directed to mammalian FGFs were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
Therefore, only an isolated binding protein of claim 1, wherein A is an extracellular portion of angiotensin-enzyme 2 (ACE2) excluding a collectrin domain and comprising SEQ ID NO: 11 or 2, or comprising SEQ ID NO: 11 or 2 with one mutation, but not the full breadth of the claim meets the written description provision of 35 U.S.C. §112, first paragraph. Applicants are reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (pg 1115).
Note on Prior Art Rejection(s)
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 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.
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.
(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.
Claims 1-4, 6-10, 12-17 and 24 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Li et al, U.S. Patent Application Publication 2023/0348880, published 11/2/23, filed 2/27/21 and claiming priority to 2/27/20. The earliest date to which the instant application claims priority is 4/3/20.
Claim 1 encompasses an isolated binding protein (BP) that binds to ACE2-targeted viruses having an amino acid sequence comprising Formula I, which is A-(B)n-C, wherein A is an extracellular domain (ECD) of angiotensin-converting enzyme 2 (ACE2) excluding the collectrin domain; B is a polypeptide flexible linker; n is from 1 to 25; and C is an Fc domain; and wherein the BP dimerizes. As an example of an ACE2 ECD excluding the collectrin domain, the specification teaches SEQ ID NO: 11, a sequence of 597 amino acids corresponding to residues 19-615 of the full-length protein shown in Figure 15. The instant specification does not provide a limiting definition of “a polypeptide flexible linker”, and as such the term is interpreted broadly an encompassing any polypeptide sequence.
Li teaches an ACE2-Fc fusion protein comprising soluble ACE2 and having the ability to neutralize SARS-CoV2 (¶ 9) by binding to the coronavirus (¶ 10). Li further teaches that the soluble ACE2 may be residues 19-615 of the full-length protein (¶ 11). Li further teaches that the Fc domain promotes dimerization (¶ 32). Li further teaches that multiple soluble ACE2 proteins, including “2n (n is 1, 2, or 3)”, may be linked to the N-terminal end(s) of two heavy chain Fc domains (¶ 34), and that each set of two soluble ACE2 domains can be linked in tandem at the N-terminal end (¶ 36), i.e., ACE2-ACE2-Fc. In such a construct, the second, internally-located soluble ACE2 domain attached to the N-terminus of the Fc domain meets the limitation directed to a “polypeptide flexible linker” recited in the instant claim. As such, Li teaches an isolated binding protein (BP) that binds to ACE2-targeted viruses (i.e., SARS-CoV2) having an amino acid sequence comprising Formula I, which is A-(B)n-C, wherein A is an extracellular domain (ECD) of angiotensin-converting enzyme 2 (ACE2) excluding the collectrin domain (i.e., ACE2 ECD residues 19-615); B is a polypeptide flexible linker (i.e., a second copy of the ACE2 ECD); n is from 1 to 25 (i.e., 1, 2 or 3); and C is an Fc domain; and wherein the BP dimerizes. As such, the teachings of Li anticipate claim 1.
Claim 2 encompasses a BP of claim 1 wherein “n” is “selected such that the distance between the A domains of the dimers is greater than 14 nm”. The average length of an amino acid is on average 0.35 nm, a linker that is an ACE2 ECD that is 596 amino acids in length as described above for claim 1 would have a length of approximately 209 nm. Thus, the teachings of Li that anticipate claim 1 above also anticipate claim 2.
Claim 3 encompasses a BP of claim 1 wherein the Fc domain is a human IgG Fc domain. Li further teaches that the Fc domain is from human IgG1 (¶ 9). As such, the teachings of Li also anticipate claim 3.
Claim 4 encompasses a BP of claim 2 wherein the Fc domain is a human IgG1 Fc domain. As described above for claim 3, Li further teaches such a domain. As such, the teaching of Li that anticipate claims 1 and 2 also anticipate claim 4.
Claims 6-8 encompass a BP of claim 1 wherein the ACE2 ECD is a protein of SEQ ID NO: 11 (residues 19-615). The teachings of Li set forth above are directed to fusion protein comprising residues 19-615 of ACE2. As such, the teachings of Li that anticipate claim 1 also meet the limitations of claims 6-8.
Claims 9 and 10 encompass a BP of claim 1 wherein the ACE ECD comprises at least one mutation (claim 9), which is a range encompassing one or more mutations, or two or more mutations (claim 10), which is a range encompassing two or more mutations. Li further teaches that the ACE2 of the invention found in the fusion protein may have mutations at positions 374 and/or 378 (¶ 15), which meets the further limitations of claims 9 and 10. As such, the teachings of Li that anticipate claim 1 also anticipate claims 9 and 10.
Claim 12 encompasses a BP of claim 1 further comprising a hinge between the liker and the Fc domain. Li further teaches that the Fc domain has a hinge region at its N-terminus (¶ 31). As such, the teachings of Li also anticipate claim 12.
Claims 13 and 14 each encompass a binding protein of claim 1, wherein the Fc domain comprising an oligosaccharide having a G0 glycosylation pattern comprises a biantennary core glycan structure of Manα1-6(Manα1-3)Manβ1-4GlcNAcβ1-4GlcNAcβ1 with terminal N-acetylglucosamine (N-GlcNAc) on each branch that enhances the trapping potency of the binding protein in mucus. Such a limitation is met by a Fc domain comprising an oligosaccharide having G0 glycosylation pattern, because such a pattern by definition comprises the recited structure (See Figures 4 and 5 of Raju et al, 2003. BioProcess International. 44-53), and thus will inherently have the enhanced trapping potency provided by the terminal N-GlcNAcs. Li further teaches that the fusion protein can be expressed in a CHO cell (¶ 90, claim 65). Expression in a CHO cell will inherently include a G0 glycosylation pattern on the Fc portion (see page 48 of Raju et al, 2003. BioProcess International. 44-53). As such, the teachings of Li also anticipate claims 13 and 14.
Claim 15 encompasses a pharmaceutical composition comprising a BP of claim 1 and a pharmaceutically acceptable excipient. The term “excipient” encompasses a “carrier”. Li further teaches that a pharmaceutical composition comprising a fusion protein of the invention and a pharmaceutically acceptable carrier (¶ 95). As such, the teachings of Li also meet the limitations claim 15.
Claims 16 and 17 encompasses a composition of claim 16 wherein the excipient is configured for inhalation (claim 16) or the composition is configured for inhalation (claim 17). Li further teaches that the medicament of the invention can be administered by inhalation (¶ 101), and therefore the composition and any excipient comprised therein would necessarily be configured for inhalation administration. As such, the teachings of Li also meet the limitations claims 16 and 17.
Independent claim 24 encompasses a BP having the same limitations as claim 6 depending from independent claim 1. As such, the teachings of Li described above that anticipate claim 6 also anticipate claim 24.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived 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 at the time any inventions covered therein were effectively filed 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 at the time a later invention was effectively filed 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 5 is rejected under 35 U.S.C. 103(a) as being unpatentable over Li et al, U.S. Patent Application Publication 2023/0348880, published 11/2/23, filed 2/27/21 and claiming priority to 2/27/20, as applied to claim 1 above, and further in view of Oganesyan et al, 2009. Molecular Immunology. 46: 1750-1755.
Claim 5 encompasses a BP of claim 1 wherein the Fc domain comprises a YTE mutation.
The teachings of Li that anticipate claim 1 are described. Li does not further teaches that the BP has an Fc domain comprising a YTE mutation.
Oganesyan teaches that YTE is a mutation of three residues that when “introduced into the CH2 domain of human immunoglobulin G (IgG) molecules, increases the serum half-life (see Abstract). Oganesyan further teaches that the “introduction of YTE into therapeutic IgGs could potentially provide many benefits such as the ability to decrease their administration frequency or dosing requirements” (page 1750).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to take the BP taught by Li that anticipates claim 1 (described above) and modify it to introduce a YTE mutation into the Fc domain as taught by Oganesyan. The person of ordinary skill in the art would have been motivated to make such a change in to confer the advantages noted by Oganesyan, namely increased serum half-life, and thus reduced administration frequency or dosing requirements, to the BP taught by Li. The person of ordinary skill in the art would have had a reasonable expectation of success because Oganesyan teaches the modification as something that can be applied generally to therapeutic IgGs, and the BP of Li is a therapeutic protein comprising an Fc, which is the relevant portion of an IgG. This rationale supports a prima facie conclusion of obviousness in accord with KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (2007).
Claim 11 is rejected under 35 U.S.C. 103(a) as being unpatentable over Li et al, U.S. Patent Application Publication 2023/0348880, published 11/2/23, filed 2/27/21 and claiming priority to 2/27/20, as applied to claim 1 above, and further in view of Chen et al, 2013. Advanced Drug Delivery Reviews 65: 1357-1369.
Claim 11 encompasses a binding protein of claim 1, wherein the polypeptide flexible linker has the sequence of GGGGS.
The teachings of Li that anticipate claim 1 are described. As set forth therein, Li teaches an ACE2-ACE2-Fc fusion protein containing two copies of the ACE2 protein linked in tandem to the N-terminus of the Fc domain, and the second ACE2 protein meets the definition of the “flexible linker” of the instant claims. Li further teaches that the two ACE2 proteins may be “linked in tandem via a linker” (¶ 37). Li does not teach that such a linker has the sequence of GGGGS as recited in claim 11.
Chen, in a review of protein linkers, teaches that “an example of the most widely used flexible linker has the sequence “(Gly-Gly-Gly-Gly-Ser)n” (page 1360). Chen teaches that such linkers can be used to “achieve appropriate separation” of functional domains, by “adjusting the copy number “n”” (page 1360).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to take the BP taught by Li that anticipates claim 1 (described above) and modify it to use a GGGGS linker as taught by Chen for the linker between the first and second ACE2 proteins in the fusion protein taught by Li.. The person of ordinary skill in the art would have been motivated to make such a change in to optimize the separation between the two ACE2 functional domains in the tandem ACE2-ACE2-Fc protein taught by Li. The person of ordinary skill in the art would have had a reasonable expectation of success because Li suggests use of a linker, and Chen teaches that the GGGGS linkers are the most widely used linkers in the relevant prior art. This rationale supports a prima facie conclusion of obviousness in accord with KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (2007). Such an ACE2-linker-ACE2-Fc protein would meet the limitation of claim 11 because the “linker-ACE2” portion of the protein would meet the further limitation of the flexible polypeptide linker having the sequence GGGGS.
Conclusion
No claims are allowable.
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/ZACHARY C HOWARD/Primary Examiner, Art Unit 1674
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