DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
The amended claims filed 03/20/2026 are acknowledged and entered.
Claims 1 and 5 have been amended
Claims 8-10 are cancelled
Claims 12-13,15-28 and 31 are withdrawn.
Claims 1-7 and 11-31 are pending
Claims 1-7, 11, 14, 29-30 are examined on their merits.
Response to Amendment
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office Action.
Claim Objections - Withdrawn
Claim 8 was objected because of a typographical error and the nucleotide and/or amino acid sequences appearing in the claims are not identified by sequence identifiers in accordance with 37 CFR 1.831. Applicant cancelled claim 8 rendering this objection moot.
Specification Objections - Withdrawn
The disclosure was objected to because of the following informalities:
a) The disclosure contains an embedded hyperlink and/or other form of browser-executable code throughout the disclosure. Applicant has corrected the informalities in the substitute specification and the objection is withdrawn.
Rejections Maintained
Claim Rejections - 35 USC § 112(a) - Maintained
1. Claims 1-7, 11, 14 and 29-30 remain rejected under 35 U.S.C. 112(a) because the claims lack the written description and enablement requirements.
Applicant’s arguments have been fully considered and are not persuasive. Therefore, the rejections are maintained.
Applicant’s Arguments:
- (a) As amended, the claims provide a humanized monoclonal antibody. This humanized monoclonal antibody (i) specifically binds to the extracellular portion of human angiotensin converting enzyme 2 (hACE2); (ii) specifically inhibits binding of SARS-CoV-2 to the extracellular portion of hACE2; and (iii) does not significantly inhibit the ability of hACE2 to cleave angiotensin II and/or a synthetic MCA-based peptide.
In relevant part, the Examiner alleges a lack of disclosed structure regarding the present antibody. In response, however, applicant stresses that a humanized antibody is structurally unique and distinct from all non-human antibodies. Put differently, to characterize the claimed antibody as "humanized" is to characterize it structurally and not just functionally.
Examiner’s Response to Traversal: Applicant’s arguments have been carefully considered but are not found persuasive.
The addition in claim 1 of the term "humanized” to the instant invention does not give any indication of what the structure is to establish the structure/function relationship under the 112(a) rejection. The humanized monoclonal antibody is only defined by the claimed functions ((i) specifically binding to a specific epitope of hACE2, (ii) inhibiting binding of SARS-CoV-2 to the extracellular portion of hACE2, and (iii) not significantly inhibiting the ability of hACE2 to cleave angiotensin II and/or a synthetic MCA-based peptide), which involve the general function of binding to an epitope. As, explained in detail in the Claim Rejections - 35 USC § 112(a) rejections in the Non final application dated 10/02/2025, the amino acid sequence (such as the CDRs found in an antibody is needed for the structure function relationship (see Amgen v. Sanofi). Any type of antibody binds to its epitope through its CDRs, which need to be 6 for monoclonal antibodies: 3 CDRS for the heavy chain and 3 CDRs for the light chain, whereas humanized or not. The specification does not disclose the amino acids sequences of the 6 CDRs found in one monoclonal antibody, Therefore the requirements needed to overcome both the written description and enablement rejections are not met.
Claim Rejections - 35 USC § 103 - Maintained
2. Claims 1-7, 11, 14 and 29-30 are rejected under 35 U.S.C 103 as being unpatentable over Ostrov (previously cited) in view of Loibner (previously cited).
Applicant’s arguments have been fully considered and are not persuasive. Therefore, the rejections are maintained.
Applicant’s Arguments:
- (a) Ostrov does not teach humanized anti-hACE2 antibodies. Instead, and importantly, Ostrov teaches humanized antibodies that instead target SARS-Co V-2. For example, in paragraph [18], Ostrov states that "In some embodiments, an ACE2-SARS interaction inhibitor comprises an anti-SARS-CoV-2 spike protein monoclonal antibody, or an epitope binding fragment thereof, wherein the anti-SARS-CoV-2 spike protein monoclonal antibody, or an epitope binding fragment thereof, binds to one or more amino acids in the region of amino acids 492-503 (LQSYGFQPTNGV (SEQ ID NO: 1) - predicted ACE2-SARS interaction domain) of the SARS-CoV-2 coronavirus spike protein.". In paragraph [121], Ostrov states that "Anti- LQSYGFQPTNGV (SEQ ID NO: 1) and anti-KFNHEAEDLFYQ (SEQ ID NO: 2) antibodies can be made using methods known in the art. In some embodiments, the antibodies can be chimeric or humanized." For at least this reason, Ostrov would have taught away from the claimed antibody.
- (b) Loibner does not overcome the shortcomings of Ostrov. In essence, this reference merely teaches an anti-hACE2 "binding unit" (e.g., an immobilized antibody) as a research tool for measuring ACE2 activity.
- (c) As for Sato, applicant notes that this reference is not prior art against the claims now under examination. Specifically, claim 8 has been canceled herein and, as the Examiner concedes, the present application's April 13, 2020, priority date applies to the remaining claims under examination. Since Sato is only entitled to an April 27, 2020, priority date, that reference is not prior art against the claims now under examination.
Examiner’s Response to Traversal: Applicant’s arguments have been carefully considered but are not found persuasive for items (a) and (b).
- Regarding (a) The Applicant argues that Ostrov does not teach humanized anti-hACE2 antibodies but teaches humanized antibodies that instead target SARS-Co V-2 in paragraph [18] and these antibodies bind the ACE2-SARS interaction domain. However, as discussed in the Non final action dated 10/02/2025 it is in paragraphs 13 and 19 where Ostrov teaches the embodiments for the anti-hACE2 antibodies. For example, paragraph 13 teaches the identification of regions of ACE2 and SARS-Co V-2 spike (S) protein that are important in binding of SARS-Co V-2 to ACE2. Antibodies directed to these sites in ACE2 (that is anti-hACE2 antibodies) and/or SARS-CoV-2 spike protein can be used to inhibit binding of SARS-Co V-2 to ACE2. Paragraph 19 teaches an ACE2-SARS interaction inhibitor comprising an antiACE2 monoclonal antibody, or an epitope binding fragment thereof. Ostrov discloses that the anti-hACE2 monoclonal antibodies bind to one or more amino acids in the region of amino acid residues 31-42 of ACE2 [118, 120, 198-199; Figure 1] as required by instant claims 4-7 (it does not bind either to the elected residue His374.or to the elected region 290-307. It does bind to the residues Lys31, His34, Glu35, Glu37, Asp38, Tyr41, Gln42, of claim 7). In addition, Ostrov’s antibodies can be humanized [121]. Therefore, Ostrov does not teach away from the claimed antibody.
- Regarding (b) One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
In summary, Loibner teaches a binding unit being preferably a monoclonal antibody that: (a) specifically binds to the extracellular portion of hACE2. Loibner teaches a binding unit specifically binding at least 8 consecutive amino acids of the 373 N-terminal amino acids of ACE2 or of the 362 C-terminal amino acids of ACE2, such a sequence against which an ACE2-binding unit can be directed is EFLGIQPTLGPPN of SEQ ID NO: 2; (these residues correspond to residues 723 to 735 and (b) does not significantly inhibit the ability of hACE2 to cleave angiotensin II (that is, the binding unit is specific for a part of ACE2 which is not involved in the catalytic activity of ACE2). Since Loibner’s monoclonal antibody binds the residues 723 to 735, it does not specifically bind to an epitope in on hACE2 consisting of residues 290 to 397 including His 374. In addition, Loibner teaches the use of a hACE substrate with a fluorescence part and a fluorescence-quenching part which can be cleaved by hACE and when cleaved the fluorescence part of the cleaved substrate is freed from the part containing the fluorescence- quenching moiety. This, in turn, results in the now unquenched substrate emitting a detectable fluorescent signal (the “synthetic MCA-based peptide” is defined in the instant application).
Applicant has not sufficiently described why there is no prima facie case for obviousness. See the Non Final action dated 10/02/2025 for more details regarding the teachings of both Ostrov, Loibner relevant to the rejection under 35 U.S.C. 103 and the motivation to combine these references.
- Regarding (c) In the Non final action dated 10/02/2025, support for the instantly claimed monoclonal anti-hACE2 antibody comprising a heavy chain complementarity determining region 3 (CDR3), as recited in claim 8, was not found in the provisional priority documents. Accordingly, the PCT/US21/26780 filing date of October 12, 2021 was considered the priority date for claim 8 for the purposes of applying prior art. Since claim 8 has been cancelled, examiner agrees that Sato’s teachings are no longer applicable for the above rejection.
Applicant argues as set forth above. Thus, for the reasons set forth above and the reasons of record, the rejection is maintained.
Double Patenting- Maintained
3. Claims 1-7, 11, 14 and 29-30 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 10-12, 15 and 30-31 of co-pending Application No. 17/499,012 (reference application).
Claims 1-7, 11, 14 and 29-30 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 10-12, 17, and 32-34 of co-pending Application No. 18/698,856 (reference application).
These are provisional nonstatutory double patenting rejections because the patentably indistinct claims have not in fact been patented. Applicant has requested that this provisional double patenting rejection be held in abeyance until the claims are otherwise allowable.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/IMMA BARRERA/
Examiner, Art Unit 1671
/BENJAMIN P BLUMEL/Primary Examiner, Art Unit 1671
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