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/Restriction
Applicant’s Response to Restriction Requirement, filed 05 August 2025, in response to the Office Action dated 24 June 2025, is acknowledged.
In the Response to Restriction Requirement, Applicant has elected Group I, claims 43-49. Claims 50-60 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05 August 2025.
Claim Status
Claims 43-60 were pending in the present application. In response to the Office’s Restriction Requirement, Applicants elected the invention in Group I, claims 43-49. As a result, claims 50-60 were withdrawn from consideration. Therefore, claims 43-49 are now pending and currently under examination.
Priority
Acknowledgment is made of applicant's claim for priority based on a parent application
filed on 30 March 2020.
The instant application filed on 29 September 2022 is a 371 of PCT/US2021/24786 filed
30 March 2021, which is a provisional of application 63/001,882 filed 30 March 2020 and which
finds full support for the instant claims. Therefore, the effective filing date of the instant
application is 30 March 2020.
.
Information Disclosure Statement (IDS)
The IDS (1) filed on 06 August 2025 has been considered by the examiner. A signed copy is enclosed.
Applicant is reminded of their duty to disclose to the Office all information known to the
person to be material to patentability as defined in 37 CFR 1.56. As stated therein, “[e]ach
individual associated with the filing and prosecution of a patent application has a duty of candor
and good faith in dealing with the Office, which includes a duty to disclose to the Office all
information known to that individual to be material to patentability as defined in this section.”
Claim Rejections - 35 USC § 112(a)
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 43-49 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a full-length synthetic cellular receptor peptide selected from ACE2, CD147, CD107a, CD13, GRP78, and DPP4, and fused to an antibody Fc domain, does not reasonably provide enablement for the amount of variance within the amino acid sequence and nucleotide sequence contained within instant claims 43, 44, and 45. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims.
The specification disclosure is insufficient to enable one skilled in the art to practice the
invention as claimed without an undue amount of experimentation. Undue experimentation must
be considered in light of factors including: the breadth of the claims, the nature of the invention,
the state of the prior art, the level of one of ordinary skill in the art, the level of predictability in
the art, the amount of direction provided by the inventor, the existence of working examples, and
the quantity of experimentation needed to make or use the invention, see In re Wands, 858 F.2d
at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988). In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24
(CCPA 1970) states, “The amount of guidance or direction needed to enable the invention is
inversely related to the amount of knowledge in the state of the art as well the predictability in
the art.” “The “amount of guidance or direction” refers to that information in the application, as
originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and
the more predictable the art is, the less information needs to be explicitly stated in
the specification. In contrast, if little is known in the prior art about the nature of the invention
and the art is unpredictable, the specification would need more detail as to how to make and use
the invention in order to be enabling” (MPEP § 2164.03). The MPEP further states that
physiological activity can be considered inherently unpredictable. With these teachings in mind,
an enabling disclosure, commensurate in scope with the breadth of the claimed invention, is
required.
In instant claim 43, Applicant has claimed an amino acid sequence representative of a peptide that comprises: 1) a synthetic cellular receptor peptide of ACE2, CD147, CD107a, CD13, GRP78, or DPP4, a fragment thereof, or a variant thereof; 2) wherein the synthetic cellular receptor peptide, fragment thereof, or variant thereof, is fused to an antibody Fc domain; and 3) wherein the synthetic cellular receptor peptide, fragment thereof, or variant thereof, specifically binds to a coronavirus Spike antigen.
In instant claim 44, Applicant has claimed an amino acid sequence representative of the entire fusion molecule including the synthetic cellular receptor peptide fused to an antibody Fc domain. Instant claim 44 allows for as little as 30% identity to the claimed sequences in SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, or 18.
In instant claim 45, Applicant has claimed a nucleotide sequence that encodes the entire fusion molecule including the synthetic cellular receptor peptide fused to an antibody Fc domain. Instant claim 45 allows for as little as 30% identity to the claimed sequences in SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, or 17.
It is unclear how the variations described by instant claims 43, 44, and 45 would allow the synthetic cellular receptor peptide to retain its binding properties to a coronavirus spike antigen. For example:
The “antibody Fc domain,” as defined by the applicant, is the Fc region of immunoglobulin selected from: IgG1, IgG2, IgG3, IgG4, IgM, IgA, IgE, or IgD (Specification, page 27). The antibody Fc domain of IgD has 226 amino acid residues1 and the antibody Fc domain of IgA1 has 245 amino acid residues.2
The spike protein of SARS-CoV-2 is composed of two subunits, S1 and S2, where the S1 subunit contains a receptor-binding domain that recognizes and binds to the large membrane-distal face of host receptor ACE-2 at residues 19-54.3
Finally, Applicant’s currently claimed sequences are comprised of the following:
SEQ ID NO
Total a.a. residues
SEQ ID NO
Total bases
2
873
1
2625
4
393
3
1185
6
389
5
1173
8
393
7
1185
10
389
9
1173
12
393
11
1185
14
393
13
1185
16
393
15
1185
18
393
17
1185
Take, for example, SEQ ID NO: 4, which is comprised of 393 total amino acid residues. A sequence variant of 30% identity, as part of the limitation of instant claim 44, would share only 118 amino acid residues with SEQ ID NO: 4. However, the Fc domain of IgD has 226 amino acid residues and the portion of ACE2 necessary for spike protein binding has 36 amino acid residues. Even at full length, SEQ ID NO: 4 only has 393 total amino acid residues while both the claimed Fc domain and the domain necessary for the claimed property of the peptide – both necessary to meet the limitations of instant claim 43 – have 262 total amino acid residues. It is unclear how one of ordinary skill in the art could produce a sequence containing 118 amino acid residues (30% of SEQ ID NO: 4) when 262 amino acid residues (Fc residues + ACE2 binding residues) are necessary to meet the characteristics and binding properties of the peptide-Fc construct as currently claimed.
Furthermore, prior art fails to provide specific guidance on these variations and actually teaches against such broad limitations. For instance, Bremel4 discloses a fusion complex where a peptide of the Ebola virus, VP40, is fused to an immunoglobulin Fc region [0338]. One of the fusion constructs disclosed by Bremel, VP40-273-314-Lin10-hFc represented by SEQ ID NO: 423, shares a 61.8% similarity to SEQ ID NO: 4 as shown below:
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Although the fusion construct disclosed by Bremel meets the limitations as currently claimed in terms of sequence identity, the construct does not meet the required binding properties as required by instant claim 43.
Based on what is disclosed in the prior art as necessary to meet the properties as to what is instantly claimed, the instant specification must provide a sufficient and enabling disclosure commensurate in scope with the instant claims. It would require an enormous amount of trial and error in order to obtain a molecule, comprised of an antibody Fc domain and synthetic cellular receptor peptide, which specifically binds to a coronavirus Spike antigen, and which only shares 30% sequence identity to the disclosed sequences. Thus, it would require undue experimentation to practice the full scope of the claimed method.
The specification is silent on this matter. Specifically, the specification only provides hypothetical experimental designs and not actual experiments or corresponding data. The disclosure does not provide a single example representative of what is instantly claimed.
Accordingly, in the absence of substantive direction or guidance in the instant
specification, the entire scope of experimentation required to develop a construct comprising a synthetic cellular receptor peptide of ACE2, CD147, CD107a, CD13, GRP78, and DPP4, fused to an antibody Fc domain, that specifically binds to a coronavirus Spike antigen, is left to those skilled in the art. Given the unpredictability in altering a single amino acid or combinations thereof, the present claims and disclosure amounts to an invitation to the skilled artisan to develop such embodiments. Furthermore, given the resource intensive nature of the required experimentation, the skilled artisan would reasonably conclude that such experimentation would be unnecessarily, and improperly, extensive and undue.
Claims 46-49 are included in the rejection because they depend from, or otherwise require, all the limitations of a rejected independent claim.
Claim Rejections - 35 USC § 112(a)
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 43-49 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 claims contain
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.
Instant claim 43 is drawn to an amino acid sequence representative of a peptide that comprises: 1) a synthetic cellular receptor peptide of ACE2, CD147, CD107a, CD13, GRP78, or DPP4, a fragment thereof, or a variant thereof; 2) wherein the synthetic cellular receptor peptide, fragment thereof, or variant thereof, is fused to an antibody Fc domain; and 3) wherein the synthetic cellular receptor peptide, fragment thereof, or variant thereof, specifically binds to a coronavirus Spike antigen.
Instant claim 44 is drawn to an amino acid sequence representative of the entire fusion molecule including the synthetic cellular receptor peptide fused to an antibody Fc domain. Instant claim 44 allows for as little as 30% identity to the claimed sequences in SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, or 18.
Instant claim 45 is drawn to a nucleotide sequence that encodes the entire fusion molecule including the synthetic cellular receptor peptide fused to an antibody Fc domain. Instant claim 45 allows for as little as 30% identity to the claimed sequences in SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, or 17.
As stated above, Applicant has claimed constructs containing: 1) a synthetic cellular receptor peptide of ACE2, CD147, CD107a, CD13, GRP78, or DPP4, a fragment thereof, or a variant thereof; 2) wherein the synthetic cellular receptor peptide, fragment thereof, or variant thereof, is fused to an antibody Fc domain; and 3) wherein the synthetic cellular receptor peptide, fragment thereof, or variant thereof, specifically binds to a coronavirus Spike antigen. There is no evidence from the disclosure the applicant was in possession of a single construct with no substitutions, let alone a construct that shares only 30% identity to that which is currently identified by the disclosed sequences. Applicant has only provided hypothetical experiment strategies lacking disclosure of a single construct.
A person of ordinary skill in the art at the time of filing would understand
residues within the construct are integral to maintaining the structure of the region that binds to the S1 RBD domain responsible for coronavirus spike protein binding. However, as shown above, a sequence that shares 30% identity to SEQ ID NO: 4 only contains 118 amino acid residues while Fc domain and ACE2 domain responsible for binding contains 262 amino acid residues. As there is no art-recognized correlation between structure and function, and prior art actually teaches away from such variations in Bremel, it would be impossible for one of ordinary skill in the art to predict which regions are integral to functional properties that would result in a structure which binds to a coronavirus spike antigen. Overall, based on the disclosure and the
state of the art at the time of filing, a skilled artesian would have recognized that the Applicant
was not in possession of the claimed invention at the time of filing.
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 43 and 46 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. (a)(2) as being anticipated by Batlle (US 2018/0230447 A1, published: 16 August 2018).
Batlle discloses active low molecular weight variants of ACE2 (abstract). Specifically, Batlle discloses an ACE2 fusion protein where ACE2 is fused to an antibody Fc domain as shown below:
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368
819
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(Fig. 10 described in [0018]; see also [0098]).
Regarding instant claim 43, Batlle discloses ACE2 fused to a monomeric soluble CH3 Fc domain ([0131]). Furthermore, Batlle discloses the method of producing this ACE2-mCH3 construct by synthesized, cloned into a vector, and overexpressed in mammalian cells lines ([0132]) indicating Batlle possessed the nucleotide sequence of the ACE2-mCH3 fusion construct as required by instant claim 43.
Regarding instant claim 46, Batlle discloses the nucleic acid molecule of ACE2-Fc fusion protein comprises an expression vector ([0132]).
Therefore, Batlle anticipates instant claims 43 and 46.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 47-49 are rejected under 35 U.S.C. 103 as being unpatentable over Batlle (US 2018/0230447 A1, published: 16 August 2018).
The teachings of Batlle are discussed above.
Regarding instant claim 47 and 49, Batlle discloses the embodiments can include pharmaceutical compositions ([0057]) that may include excipients ([0058]).
Regarding instant claim 48, Batlle discloses the ACE-Fc dimerizes through the hinge region of the Fc tag forming a multimeric complex as shown below (Fig. 10, [0018]).
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833
200
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It would have been prima facie obvious, before the effective filing date of the claimed invention, to use the disclosures made by Batlle to arrive at the currently claimed invention. Batlle discloses an identical construct as to what is currently claimed. Furthermore, Batlle provides embodiments of the disclosure such as use within a pharmaceutical composition. Therefore, one of ordinary skill in the art could easily select from the embodiments disclosed by Batlle with reasonable expectation of success because Batlle explicitly discloses each of the limitations contained within instant claims 47-49.
Claims 44 and 45 are rejected under 35 U.S.C. 103 as being unpatentable over Batlle (US 2018/0230447 A1, published: 16 August 2018) in further view of Sambrook (Molecular Cloning A Laboratory Manual, 2nd edition, Cold Spring Harbor, N.Y., 1989, pages 2.43-2.84) and Jaye (Nucl Acids Res 11(8): 2325-2355, 1983).
The teachings of Batlle are disclosed above.
Regarding instant claims 44 and 45, Batlle discloses an ACE2-Fc fusion protein represented by SEQ ID NO: 3. Instant SEQ ID NO: 2 is 68.6% identical to SEQ ID NO: 3 of Batlle as shown below:
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814
490
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Both instant SEQ ID NO: 2 and Batlle SEQ ID NO: 3 contain the amino acid residues 19-617 of the full-length ACE2 peptide. Although Batlle does not explicitly disclose the ACE2-Fc fusion protein binds to a coronavirus spike antigen, Battle discloses a structure meeting the limitations as to what is currently claimed. Therefore, the property of binding to a coronavirus spike antigen is inherent to the claimed sequence.5 See MPEP 2112(III).
Batlle discloses an ACE2-Fc construct, represented by amino acid sequence SEQ ID NO: 3, that is 68.6% identical to what is instantly claimed. However, Batlle does not disclose the nucleotide sequences which encode the currently claimed sequences.
One of ordinary skill in the art has the basic knowledge that there are sets of three nucleotides that make up a codon and 61 of the 64 possible combinations of three bases are used to code for specific amino acids (the other three code for stop signals). Therefore, one of ordinary skill in the art could determine the corresponding nucleic acid sequence from the amino acid sequence disclosed by Batlle in view of the methods taught by Sambrook (Molecular Cloning A Laboratory Manual, 2nd edition, Cold Spring Harbor, N.Y., 1989, pages 2.43-2.84) and Jaye (Nucl Acids Res 11(8): 2325-2355, 1983). One skilled in the art can also use commercially available computer software to translate the peptide sequences of Batlle to nucleic acid sequences (see for example, U.S. Patent 6,399,857; column 6, lines 50-57). Therefore, in light of the combined references, the instant invention claiming the nucleotide sequence which encodes the ACE2-Fc construct sequence disclosed by Batlle would have been prima facie obvious to one of ordinary skill in the art at the time of the claimed invention.
Conclusion
Claims 43-49 are rejected. No claim is allowed.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Julia A Rossi whose telephone number is (571) 272-0138. The examiner can normally be reached M-F 8:30-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Daniel E Kolker can be reached at (571) 272-3181. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JULIA A ROSSI/Examiner, Art Unit 1644
/DANIEL E KOLKER/Supervisory Patent Examiner, Art Unit 1644
1 Shinoda et al. “Complete amino acid sequence of the Fc region of a human δ chain.” Proc Natl Acad Sci U S A. 1981 Feb;78(2):785–789. doi: 10.1073/pnas.78.2.785. See page 785, abstract.
2 Putnam et al. “Primary structure of a human IgGA1 immunoglobulin.” IV. Streptococcal IgA1 protease, digestion, Fab and Fc fragments, and the complete amino acid sequence of the alpha 1 heavy chain. J Biol Chem. 1979 Apr 25;254(8):2865-74. PMID: 107164. See page 2867.
3 Wrobel, A.G. (2023). “Mechanism and evolution of human ACE2 binding by SARS-CoV-2 spike.” Current opinion in structural biology, 81, 102619. https://doi.org/10.1016/j.sbi.2023.102619. See page 6.
4 US 2017/0161430 A1, published: June 8, 2017.
5 This is further evidenced by the previously discussed portion of ACE2 responsible for binding to the coronavirus spike antigen occurring at residues 19-54, which are present in Batlle SEQ ID NO: 3.