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
Applicant's election with traverse of Group II (i.e., claims 7 and 14-22 directed to a polypeptide derivative) in the reply filed on May 15, 2025, is acknowledged.
The traversal regarding the groupings is on the grounds that the amendments to claims 1 and 7 such that options (2) and (3) in each claim constitute a reasonable extension of derivatives based on SEQ ID NOs: 1 and 2, respectively (See Applicant’s Response received on 5/15/25, pg. 5). As such, by setting appropriate parameters, the retrieval of such variants does not require undue effort. Thus, Groups I and III, and II and IV share specific technical features (See Applicant’s Response received on 5/15/25, pg. 5). Furthermore, Applicant asserts that HR2P and EK1 share similar mechanisms of action in inhibiting SARS-CoV-2 by targeting the same binding site, and thus, Groups I and II satisfy the requirement of unity of invention (See Applicant’s Response received on 5/15/25, pg. 5).
This is not found persuasive. Regarding Groups I and II, as discussed in the Restriction mailed on 3/18/25, the two groups do not share the same or corresponding technical feature as Groups I and II are directed to different amino acid sequences, i.e., SEQ ID NO: 1 and 2, respectively. As stated in the Restriction, there is no shared structure or sequence between SEQ ID NOs: 1-2. Rather, they are 40% identical thereby not constituting a polypeptide of (1), (2) or (3) in either claims 1 or 7. Therefore, without a shared core structure or sequence, there is no way for a determination of a shared technical feature between Groups I and II.
Regarding Groups I/III and II/IV, it is noted that Groups III is directed to a method of using the polypeptide of Group I and Group IV is directed to a method of using the polypeptide of Group II. Although narrowing the number of amino acid modifications to 2-5 or at least 85% identity, the standards of Rule 13.2 apply, which examines whether the alternatives of a Markush group are of a similar nature. The standard is not whether there is an undue search burden as suggested by Applicants (i.e., undue effort). As stated in the Restriction mailed on 3/18/25, even if the alternatives of options (1), (2), and (3) have a common property or activity, which the Examiner does not concede (A), the alternatives do not share a common structure as the 2-5 amino acid modifications (substitutions, deletions, additions or insertions) can occur anywhere in the sequence (B)(1). Additionally and/or alternatively, there is no evidence to demonstrate that there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention.
Additionally, Applicant's election with traverse of Species B (i.e., SEQ ID NO: 2 as the polypeptide with a cholesterol modification performed at the C-terminus of the polypeptide and where the cholesterol moiety is conjugated to the C-terminus via –(GSGSG)n-DPEG4- as a linker where n is 1 thereby resulting in the polypeptide derivative of SLDQINVTFLDLEYEMKKLEEAIKKLEESYIDLKEL-(GSGSG)-DPEG4-cholesterol) in the reply filed on May 15, 2025, is acknowledged.
The traversal regarding the groupings is on the grounds that (1) modifications of SEQ ID NO: 2 to obtain derivatives and their use in the treatment of SARS-CoV-2 is nonobvious based on the prior art, (2) the variant derivatives in items (2) and (3) of claim 7 represent reasonable extensions of the derivatives based on SEQ ID NO: 2, and (3) the modification sites, the use of a linker, and the specific type of linker employed constitute routine choices for a person skilled in the art (See Applicant’s Response received on 5/15/25, pg. 6).
This is not found persuasive. It is noted that the species election is for a single and specific polypeptide derivative. A polypeptide derivative encompasses a vast number of species even with the narrowed scope limiting the number of amino acid modifications to 2-5. More specifically, the polypeptide derivative amino acid sequence still does not encompass a core structure or sequence that each species shares given that the 2-5 amino acid modifications (substitutions, deletions, additions or insertions) encompass any 2-5 modifications located at any position in SEQ ID NO: 2. Moreover, a fatty acid palmitoyl modification is structurally distinct from a cholesterol modification and where such a modification can occur anywhere in the polypeptide sequence. Plus, the number of linkers that may or may not conjugate a palmitoyl or cholesterol modification to a polypeptide without any shared core structure or sequence encompasses a vast array of linkers, even if many may be routine. When considering all the encompassed modifications of a polypeptide derivative of claim 7: residue modifications and palmitoyl or cholesterol modifications with our without a linker, the Examiner maintains that there is no core structure and/or sequence shared among the vast array of species that would link them together. Therefore, the Examiner maintains that the species lack unity of invention a priori.
The requirement is still deemed proper and is therefore made FINAL.
Status of Claims
Claims 1-13 were originally filed on May 17, 2022.
The amendment received on July 21, 2022, canceled claims 2-6, 10-11, and 13; amended claims 7-9 and 12; and added new claims 14-28. The amendment received on May 15, 2025, amended claims 1 and 7. The amendment received on November 18, 2025, canceled claim 2; and amended claims 7 and 18-20.
Claims 1, 7-9, 12, and 14-28 are currently pending and claims 7 and 14-22 are under consideration as claims 1, 8-9, 12, and 23-28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on May 15, 2025.
Priority
The present application claims status as a 371 (National Stage) of PCT/CN2021/071078 filed January 11, 2021, and claims priority under 119(a)-(d) to Chinese Application No. 202010080751.4 filed on February 5, 2020.
Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d) for Chinese Application No. 202010080751.4, which papers have been placed of record in the file. Please note that the Chinese application is in a foreign language and therefore cannot be verified.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on November 18, 2025, is being considered by the examiner.
Sequence Interpretation
For claim 7, please note that the Examiner is interpreting the scope of the claim as open-ended where (1) requires 100% identity with any N- and/or C-terminal additions to SEQ ID NO: 2; (2) requires an amino acid sequence that contains 2 to 5 substitutions, deletions, additions or insertions of SEQ ID NO: 2 with any N- and/or C-terminal additions, e.g., SEQ ID NO: 2 with 5 deleted residues within the sequence, but is part of a larger sequence; and (3) requires at least 85% identity to SEQ ID NO: 2 thereby encompassing up to 5 residue modifications (i.e., substitutions, deletions, additions and/or insertions), but with any N- and/or C-terminal additions.
For claim 18, please note that the Examiner is interpreting the scope of the claim as open-ended requiring 100% identity to either (GSG)n or (GSGSG)n where n is 1 or 2 with any N- and/or C-terminal additions.
For claim 19, please noted that the Examiner is interpreting the scope of the claim as closed-ended requiring 100% identity and the same length to the peptide linker component (GSG)n or (GSGSG)n where n is 1 or 2. However, it is noted that this interpretation only pertains to the linker component and not the polypeptide amino acid sequence.
For claim 20, please noted that the Examiner is interpreting the scope of the claim as closed-ended requiring 100% identity and the same length to either peptide derivative.
Response to Arguments
Applicant’s arguments, see Response, filed 11/18/26, with respect to the objection to the specification have been fully considered and are persuasive. The objection of the specification has been withdrawn.
Applicant’s arguments, see Response, filed 11/18/26, with respect to the claim objection have been fully considered and are persuasive. The objection of claims 18-20 has been withdrawn.
Applicant’s arguments, see Response, filed 11/18/26, with respect to the 112(b) rejection have been fully considered and are persuasive. The rejection of claims 19-20 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 has been withdrawn.
Applicant’s arguments, see Response, filed 11/18/26, with respect to the 102(a)(1) rejection have been fully considered and are persuasive. The rejection of claims 7 and 14-22 as being anticipated by Xia et al., Cell Res. 30:343-355 (March 30, 2020) has been withdrawn.
Maintained/Modified Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 7, 14-19, and 21-22 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. Please note that the rejection has been updated in light of Applicants’ amendments.
Independent claim 7 includes a “polypeptide comprising an amino acid sequence in which 2, 3, 4, or 5 amino acid residues are substituted, deleted, added or inserted in the SEQ ID NO: 2” or a “polypeptide comprising an amino acid sequence having at least 85% identity to SEQ ID NO: 2”. The interpretation of these phrases are described above in the “Sequence Interpretation” section where a polypeptide derivative comprising 2-5 substitutions, insertions, additions, and/or deletions of SEQ ID NO: 2 where these modifications can be located at any residue and/or location of SEQ ID NO: 2, and a polypeptide derivative having at least 85% identity to SEQ ID NO: 2 encompasses up to 5 amino acid modifications anywhere in the sequence and encompassing substitutions, insertions, additions, and/or deletions. In addition to certain manipulations of SEQ ID NO: 2, the derivative must also have exhibit the function of an inhibitory activity against coronavirus and where this inhibitory activity is 10-100 times that of the polypeptide of SEQ ID NO: 2 alone.
The written description requirement may be met by provided a representative number of species of the genus and/or in light of the state of the art. With regard to the state of the art, CN 107022008A (hereinafter referred to as ‘008 and cited in the 103 rejection below), teaches a single polypeptide derivative that exhibits inhibitory activity against coronavirus where this inhibitory activity is 10-100 times that of the polypeptide of SEQ ID NO: 2 alone, i.e., EK3 (See ‘008, Table 1). When comparing the EK3 amino acid sequence with instant SEQ ID NO: 2, there are 5 substituted residues, i.e., Ser1Asn, Leu2Pro, Asp3Gly, Gln4Asp, and Glu35Lys. However, ‘008 fails to identity a core structure or sequence that each polypeptide derivative would need in order to exhibit inhibitory activity against coronavirus. Moreover, a single species of polypeptide derivative is not sufficient to establish a representative number of species within the claimed genera. Thus, the claims are directed to peptide derivatives with a certain function but no correlated structure associated with that function. Without such structure, the specification does not convey possession of the breadth of the claimed genera.
Alternatively, the written description requirement may be met by provided a representative number of species of the genus. In this, the specification does not provide a single example of a sequence meeting the claimed limitations except for SEQ ID NO: 2 that is modified with palmitic acid or cholesterol. Figure 2 demonstrates that SEQ ID NO: 2 and SEQ ID NO: 2 modified with either palmitic acid or cholesterol exhibits inhibitory activity against 2019-nCoV where the modified SEQ ID NO: 2 derivatives exhibited 10 to 100 times the inhibitory activity of SEQ ID NO: 2, respectively (See instant, pg. 19, 1st paragraph). With respect to amino acid modifications of SEQ ID NO: 2, the specification defines an amino acid substitution as referring to the replacement of a certain amino acid residue at a certain position in the amino acid sequence by another amino acid residue as long as the polypeptide has inhibitory activity against coronavirus (See instant, pg. 8, 2nd paragraph); defines an amino acid addition as referring to the addition of amino acids to the C-terminus or N-terminus of an amino acid sequence as long as the polypeptide has inhibitory activity against coronavirus (See instant, pg. 8, 1st paragraph); defines an amino acid insertion as referring to the insertion of amino acid residues at appropriate positions in the amino acid sequence where the inserted residues may be either adjacent to each other in whole or in part, or not adjacent to each other, as long as the polypeptide has inhibitory activity against coronavirus (See instant, pg. 8, 3rd paragraph); and defines an amino acid deletion as referring to the deletion of 1 or more amino acids from the amino acid sequence as long as the polypeptide has inhibitory activity against coronavirus (See instant, pg. 8, 4th paragraph). The specification also teaches that the substitution can be a conservative substitution where conservative substitutions are depicted in Tables 1-3 (See instant, pg. 8, 5th paragraph; Tables 1-3). However, such broad description fails to establish a core structure or sequence needed for the derivative to exhibit an inhibitory activity against coronavirus where this inhibitory activity is 10-100 times that of the polypeptide of SEQ ID NO: 2 alone. Moreover, there is no indication that polypeptide derivative with 2 to 5 substitutions, additions, insertions and/or deletions would function similar to SEQ ID NO: 2 including exhibiting inhibitory activity 10-100 times that of the native SEQ ID NO: 2 sequence. Thus, this is not sufficient to constitute are a representative number of species and/or for the skilled artisan to envisage which amino acid modifications can be made with an expectation that function will be preserved.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, 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, what is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of polypeptides which preserve the required function, 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.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence. Therefore, claims 7, 14-19, and 21-22 do not meet the written description requirement.
Applicants’ Arguments
Applicants contend that the claimed invention satisfies the written description requirement because the inventive concept of the present invention lies in enhancing the antiviral effect of EK1-series polypeptides through cholesterol modification or palmitoylation of theses polypeptides via particular linkers and PEG4 (See Applicant’s Response received on 11/18/25, pg. 6-7). Moreover, Applicants assert that CN107022008A teaches in Table 1, three polypeptides: HCoV-EK1, HCoV-EK2, and HCoV-EK3, which has 5 amino acid differences compared with EK1, and exhibited varying degrees of inhibitory effects on different coronaviruses such as MERS-CoV, HCoV-229E, SARS-CoV, RsSHC014-CoV, and RsW1V2CoV (See Applicant’s Response received on 11/18/25, pg. 6-7). As such, the ‘008 reference demonstrates that these polypeptides can tolerate a certain degree of amino acid mutation while retaining their virus-inhibiting effect (See Applicant’s Response received on 11/18/25, pg. 7). Applicants also assert that the ‘008 reference fully describes methods for screening suitable polypeptides and an ordinary skilled artisan can obtain EK1-series polypeptides with high sequence identity to EK1 through convention screening methods (See Applicant’s Response received on 11/18/25, pg. 7).
Response to Arguments
Applicant's arguments filed 11/18/25 for claim 7, 14-19, and 21-22 as failing the written description requirement have been fully considered but they are not persuasive for the following reasons.
In response to Applicant’s argument that the inventive concept of the present invention lies in enhancing the antiviral effect of EK1-series polypeptides through cholesterol modification or palmitoylation of theses polypeptides via particular linkers and PEG4, it is found unpersuasive. Applicants are respectfully reminded that written description pertains to whether Applicant is in possession of the scope of the claimed invention. The alleged point of novelty of a claimed invention does not per se correlate to possession of the claimed invention. MPEP §2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
Additionally, the importance of structure/function correlations was recently highlighted by the courts (Abbvie Deutschland v. Janssen Biotech and Centorcor Biologics, App. No. 2013-1338, -1346 (Fed. Cir. , July 1, 2014)). The Abbvie case involved antibodies and written description. The court stated: “We have held that “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.” Id. at 1350 (quoting Eli Lilly, 119 F.3d at 1568– 69).”. The courts then further stated: “With the written description of a genus, however, merely drawing a fence around a perceived genus is not a description of the genus. One needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus.” (emphasis added) and then state: " Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Ariad, 598 F.3d at 1351 (“[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology.”); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1352 (Fed. Cir. 2011) (noting the technical challenges in developing fully human antibodies of a known human protein). It is true that functionally defined claims can meet the written description requirement if a reasonable structure-function correlation is established, whether by the inventor as described in the specification or known in the art at the time of the filing date. Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 964 (Fed. Cir. 2002). However, the record here does not indicate such an established correlation. Instead, Abbvie used a trial and error approach to modify individual amino acids in order to improve the IL-12 binding affinity. Moreover, the ’128 and ’485 patents do not describe any common structural features of the claimed antibodies. The asserted claims attempt to claim every fully human IL-12 antibody that would achieve a desired result, i.e., high binding affinity and neutralizing activity, and cover an antibody as different as Stelara, whereas the patents do not describe representative examples to support the full scope of the claims.”
In the instant case, it is acknowledged that the instant specification demonstrates in Figure 2 that the EK1 polypeptide when conjugated to palmitic acid or cholesterol exhibited inhibitory activity similar to the EK1 polypeptide alone but at a concentration 10 to 100 times lower than the concentration of the EK1 polypeptide alone (See instant, Figure 2). However, Applicant has not provided evidence to demonstrate that palmitic acid or cholesterol is the core structure necessary for a polypeptide derivative as claimed to exhibit inhibitory activity against a coronavirus. It is noted that there are two functional properties recited in instant claim 7; namely, the polypeptide has inhibitory activity against coronavirus, and where the inhibitory activity of the polypeptide derivative is 10-100 times that of the polypeptide of SEQ ID NO: 2. Although it is acknowledged that the conjugation of SEQ ID NO: 2 to palmitic acid or cholesterol resulted in inhibitory activity against a coronavirus at a lower concentration (See instant, Figure 2) and the inhibitory activity against several coronaviruses is enhanced (See instant, Table 5), the amino acid sequence of the two polypeptide derivatives is identical to SEQ ID NO: 2. The component of the derivative that exhibits the inhibitory activity against a coronavirus is dependent upon the polypeptide sequence, and not the palmitic acid or cholesterol. There is no evidence to establish that palmitic acid or cholesterol alone exhibits inhibitory activity against a coronavirus. As such, the variability encompassed by instant claim 7 is based on the variability of the polypeptide amino acid sequence and not the conjugation to palmitic acid or cholesterol. As stated in the rejection supra, the specification does not teach any variant/mutant/analog polypeptide sequences of SEQ ID NO: 2 that exhibit inhibitory activity against a coronavirus. Thus, given that the scope of claim 7(2) and 7(3) encompasses 2-5 amino acid modifications including deletions, substitutions and/or insertions anywhere in the amino acid sequence, the Examiner maintains that it would be difficult for a skilled artisan to envision the correlation between structure and function for the whole genera and/or to predict what would be covered by the functionally claimed genera because Applicants have failed to provide a representative number of species to support the scope of the whole genera.
In response to Applicant’s argument that CN107022008A teaches in Table 1, three polypeptides: HCoV-EK1, HCoV-EK2, and HCoV-EK3, which has 5 amino acid differences compared with EK1, and exhibited varying degrees of inhibitory effects on different coronaviruses such as MERS-CoV, HCoV-229E, SARS-CoV, RsSHC014-CoV, and RsW1V2CoV thereby demonstrating that these polypeptides can tolerate a certain degree of amino acid mutation while retaining their virus-inhibiting effect, it is found unpersuasive. Although it is acknowledged that ‘008 teaches one variant polypeptide with 5 substituted residues, Applicants have not provided evidence to support that a single variant polypeptide that has specific substitutions, i.e., the first four residues at the N-terminus and the second to last residue at the C-terminus (and no insertions and/or deletions) constitutes a representative number of species within the genera in claim 7(2) and 7(3), or that the non-substituted residues are essential to the EK1 polypeptide’s inhibitory activity against a coronavirus. As discussed in the rejection supra and pursuant to MPEP 2163.05(I)(B), [t]he written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species. A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus."). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615. "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004) (Claims directed to PTFE dental floss with a friction-enhancing coating were not supported by a disclosure of a microcrystalline wax coating where there was no evidence in the disclosure or anywhere else in the record showing applicant conveyed that any other coating was suitable for a PTFE dental floss.) As such, in the instant case, although there are situations where a single species adequately supports a genus (See MPEP 2163.05(I)(B), e.g., In re Rasmussen, 650 F.2d 1212, 1214, 211 USPQ 323, 326-27 (CCPA 1981) (disclosure of a single method of adheringly applying one layer to another was sufficient to support a generic claim to "adheringly applying" because one skilled in the art reading the specification would understand that it is unimportant how the layers are adhered, so long as they are adhered), given that the ‘008 references only teaches one specific species (i.e., EK3 polypeptide) demonstrating inhibitory activity against a coronavirus, the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed. Therefore, even if the instant specification is deemed to support possession of a single EK1 polypeptide that would fall within the scope of instant claim 7(2) or 7(3) in light of the ‘008 disclosure, Applicants have not demonstrated a representative number of species within the claimed genera of amino acid sequences of instant claim 7(2) and 7(3) to constitute possession of the claimed genera.
Accordingly, the rejection of claims 7, 14-19, and 21-22 as failing the written description requirement is maintained.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
103 - KSR Examples of 'Rationales' Supporting a Conclusion of Obviousness(Consistent with the "Functional Approach" of Graham)
Further regarding 35 USC 103(a) rejections, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) (KSR) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Also, a reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976).
Claims 7 and 14-22 are rejected under 35 U.S.C. 103 as being unpatentable over Jiang et al. CN 107022008A published on August 8, 2017 (cited in the IDS received on 11/14/23) (note: English language machine translation of CN 107022008A obtained for espacenet.com, 9 pages (2017) will be used to discuss ‘008) in view of Mathieu et al., J. Infect. Dis. 218:218-227 (2018).
For claims 7 and 20, with respect to the polypeptide amino acid sequence of SEQ ID NO: 2:
‘008 teaches polypeptides that broadly inhibit human coronavirus infection by functioning as a polypeptide entry inhibitor (See ‘008, pg. 2, 4th to 5th paragraph). The polypeptide binds to the HR1 region of the S2 protein of two or more human coronaviruses and interferes with the virus’s own six-helix formation thereby inhibiting the virus fusion process (See ‘008, pg. 2, 5th paragraph). The polypeptide has the amino acid sequence as depicted in Table 1:
PNG
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200
400
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(See ‘008, Table 1). When comparing instant SEQ ID NO: 2 with the EK1 or EK2 (residues 1-36) amino acid sequences of ‘008, there is 100% identity. Thus, the ‘008 polypeptide amino acid sequence satisfies the polypeptide amino acid sequence of SEQ ID NO: 2 as recited in instant claims 7 and 20.
For claims 7 and 14-20, with respect to where the polypeptide is obtained by cholesterol modification as recited in instant claim 7; with respect to where the cholesterol modification is performed at the C-terminus of the polypeptide as recited in instant claim 14; with respect to where the polypeptide is linked to the cholesterol moiety via a linker at the C-terminus as recited in instant claim 15; with respect to where the linker is PEGylated as recited in instant claim 16; with respect to where the polypeptide is linked to cholesterol modified cysteine via a linker at the C-terminus as recited in instant claim 17; with respect to where the linker comprises (GSGSG)n where n is 1 or 2 as recited in instant claim 18; with respect to where the linker is (GSGSG)n-PEG4- as recited in instant claim 19; and with respect to where the polypeptide derivative is SEQ ID NO: 2-(GSGSG)n-PEG4-C-cholesterol where n is 1 or 2 as recited in instant claim 20:
‘008 teaches that human coronavirus plays an essential role in the infection of target cells with its envelope glycoprotein (S protein) (See ‘008, pg. 1, 4th paragraph). The S protein can be divided into the S1 subunit and the S2 subunit (See ‘008, pg. 1, 4th paragraph). The S1 subunit is responsible for binding with its target cell whereas the S2 subunit is a N-terminal fusion peptide that is exposed to enable it to insert the target cell membrane (See ‘008, pg. 1, 4th paragraph). Once inserted, the S2 subunit induces a series of conformational changes including a N-terminal heptad repeat domain (HR1 or NHR) to form a timer and interact with its C-terminal heptad repeat domain (HR2 or CHR) to form a “fused core” or “six helix bundle” (6HB) such that the viral and target cell membrane are close enough to allow for fusion to occur (See ‘008, pg. 1, 4th paragraph). As discussed supra for claims 7 and 20, ‘008 teaches a polypeptide amino acid sequence that is 100% identical to instant SEQ ID NO: 2. ‘008 teaches that this polypeptide will inhibit viral cell entry by binding to the HR1 region of the S2 protein thereby interfering with the virus’s own six-helix formation, and thus, inhibiting the viral fusion process to a target cell (See ‘008, pg. 2, 5th paragraph).
Moreover, ‘008 teaches that the polypeptide amino acid sequence can be modified (See ‘008, pg. 2, 6th paragraph). For example the EK2 amino acid sequence depicted in Table 1 supra contains GSGGRRRRRR at the C-terminus (See ‘008, pg. 2, Table 1). As such, the GSG portion constitutes a linker with the sequence of (GSG)n where n is 1. Thus, this GSG tripeptide constitutes a linker that is covalently conjugated to the C-terminus of the polypeptide as recited in instant claims 15 and 17-18. However, ‘008 does not expressly teach that the polypeptide is modified by a cholesterol moiety modified with a cysteine at the C-terminus of the polypeptide instead of a polyarginine peptide via the linker where the linker is (GSGSG)n-PEG4 where n is 1 or 2.
Mathieu et al. engineered new antiviral lipopeptides to identify a candidate to treat paramyxovirus Nipah virus (NiV) by inhibiting viral fusion (See Mathieu, abstract). Paramyxovirus infections are initiated by fusion between viral and host cell membranes during viral entry (See Mathieu, pg. 218, col. 2, 2nd paragraph). NiV entry is mediated by the viral envelope glycoproteins G and F (See Mathieu, pg. 218, col. 2, 2nd paragraph). G-mediated attachment of the virus to target cell triggers large-scale conformational rearrangements in the F (fusion) protein, permitting the hydrophobic fusion peptide to insert into the host target cell membrane, pulling the viral and cell membranes together when the 2 heptad-repeat regions in each ectodomain of F refold to form a stable, antiparallel 6-helix bundle structure (See Mathieu, pg. 218, col. 2, 2nd paragraph). NiV F-mediated entry into target cells can be specifically targeted by fusion-inhibitory peptides that interfere with this initial step of viral entry by blocking formation of the 6-helix bundle (See Mathieu, pg. 218, col. 2, 3rd paragraph).
Mathieu et al. found that fusion inhibitory peptide entry inhibitors, if conjugated to lipid moieties linked to the amino acid sequence by a flexible linker, can be highly effective inhibitors of NiV central nervous system infection (See Mathieu, pg. 218, col. 2, 3rd paragraph). The new lipopeptides confer greater stability to protease degradation and improved efficacy in vitro and in vivo (See Mathieu, pg. 218, col. 2, 3rd paragraph). In particular, Mathieu et al. demonstrated that conjugation of peptides with a single cholesterol moiety enhanced NiV antiviral activity by targeting the peptide to the plasma membrane (See Mathieu, pg. 220, col. 1, last paragraph), and decreases protease sensitivity where the cholesterol moiety is bound to the peptide via a dPEG4 linker (See Mathieu, pg. 220, col. 2, 4th paragraph). It is noted that the dPEG4 is described as discrete PEG and was obtained from Quanta BioDesign (See Mathieu, pg. 219, col. 1, 3rd paragraph), which as discussed in the 112(b) rejection supra owns the trademark dPEG®. As such, Mathieu supports the determination that dPEG is a specific trademarked PEG moiety. The polypeptide derivative amino acid sequence and structure are depicted in Table 1A where VIKI-dPEG4-Chol as:
PNG
media_image2.png
200
400
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Greyscale
(See Mathieu, Table 1). Thus, Mathieu et al. demonstrates that when a polypeptide inhibitor of viral entry is fused to a single cholesterol moiety via GSGSG-dPEG4-C- as a linker, the efficacy and stability of the polypeptide are improved.
Additionally, Mathieu et al. teaches that this conjugation method can be broadly applied to other inhibitory viral polypeptides given that the majority of fusion proteins that mediate enveloped viral entry have molecular regions that interact to mediate virus-cell fusion that can be identified from the primary sequence, and lipopeptide fusion inhibitors can be designed on the basis of pathogen genetic information (See Mathieu, pg. 223, col. 1, 2nd paragraph). These strategies to deliver antivirals via the respiratory route, and target them to the membrane site of action can be broadly applied (See Mathieu, pg. 223, col. 1, 2nd paragraph). Furthermore, Mathieu et al. teaches that developing these fusion inhibitors would set the stage for a platform technology suitable not only for other paramyxoviruses but also for other enveloped viruses with similar entry pathways (See Mathieu, pg. 226, col. 1, 1st paragraph).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant application to modify the teachings of ‘008 and substitute the -GSGGRRRRRR modification of the EK2 polypeptide of ‘008 with the -GSGSG-PEG4-C-Chol-NH2 modification where such substitution results in the polypeptide derivative exhibiting improved efficacy against coronavirus infection and improved stability against enzymatic degradation. One of ordinary skill in the art at the time the invention was made would have been motivated to do so because the coronavirus as taught by ‘008 was known to utilize a similar mechanism to mediate virus-cell fusion and subsequent viral entry when compared to the paramyxovirus taught by Mathieu et al., and because the EK1 polypeptide of ‘008 was known to inhibit viral cell entry by binding to the HR1 region of the S2 protein thereby interfering with the virus’s own six-helix formation similar to the lipopeptide fusion inhibitors of Mathieu et al. that were known to interfere with the initial step of viral entry by blocking formation of the 6-helix bundle. One of ordinary skill in the art at the time the invention was made would have had a reasonable expectation of success given that the modified EK2 polypeptide of ‘008 was used to inhibit coronavirus entry into a target cell by blocking formation of the 6-helix bundle, and therefore, substituting the -GSGGRRRRRR modification of the EK2 polypeptide of ‘008 with the -GSGSG-PEG4-C-Chol-NH2 modification where such substitution results in the polypeptide derivative would support the improvement of the polypeptide derivative’s efficacy against coronavirus infection and stability against enzymatic degradation by constituting the simple substitution of one known element for another to obtain predictable results and/or some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention pursuant to KSR.
For claims 21-22, with respect to a composition comprising the polypeptide derivative of claim 7 as recited in instant claim 21; and with respect to where the composition is an external preparation as recited in instant claim 22:
‘008 teaches a pharmaceutical composition comprising a polypeptide of the invention, e.g., modified EK1, and optionally a pharmaceutically acceptable carrier or excipient (See ‘008, pg. 4, 8th paragraph). Thus, the teachings of ‘008 satisfy the claim limitation as recited in instant claim 21.
Moreover, ‘008 teaches in Example 2, that the polypeptide was dissolved in DMSO and applied to human coronavirus receptor target cell (HuH7) suspension in a 96 well plate using a gradient of 2 times the dilution of peptide drug in DMEM culture medium containing 10% FBS (note: assuming this should be PBS), 50µl per well (See ‘008, pg. 5, 2nd to 6th paragraph).
Although ‘008 does not expressly teach that the pharmaceutical composition is an external preparation, the dosage form (i.e., a solution that was added to each well) constitutes a dosage form that can be used as an external preparation. Pursuant to MPEP 2111.04(I), [c]laim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. However, examples of claim language, although not exhaustive, that may raise a question as to the limiting effect of the language in a claim are:
(A) “adapted to” or “adapted for” clauses;
(B) “wherein” clauses; and
I “whereby” clauses.
The court has found that the determination of whether clauses such as “wherein” and “whereby” is a limitation in a claim is dependent on the specific facts of the case. If the “wherein” or “whereby” clause limits a process claim where the clause gives meaning and purpose to the manipulative steps, it should be given patentable weight. Griffin v. Bertina, 285 F.3d 1029, 1034, 62 USPQ2d 1431 (Fed. Cir. 2002). However, the court also found (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “‘whereby clause In a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” In the instant case, the claimed preparation is intended to be administered externally thereby constituting the intended use of the preparation, and thus, the structure imparted by such a use would be one requiring the preparation to be in a form capable of external administration. Since ‘008 teaches adding a pharmaceutical composition comprising the modified polypeptide as a solution to each well in an assay, the structural limitation imparted by the “wherein” clause is met. Therefore, the teachings of ‘008 satisfy the claim limitation as recited in instant claim 22.
Accordingly the combination of ‘008 and Mathieu et al. suggest the claimed invention as recited in instant claims 7 and 14-22.
Applicants’ Arguments
Applicant contends that the claimed invention is nonobvious because (1) an ordinary skilled artisan would not have a reasonable expectation of success in arriving at the claimed invention, particularly in view of the unpredictable nature of cholesterol modification and linker optimization, and thus, the cited art do not enable a person skilled in the art to arrive at the present invention (See Applicant’s Response received on 11/18/25, pg. 8-14); and (2) the claimed invention exhibits unexpected results of enhanced inhibitory activity against a coronavirus as demonstrated in Table 5 (See Applicant’s Response received on 11/18/25, pg. 14-15).
Response to Arguments
Applicant's arguments filed 11/18/25 of claims 7 and 14-22 as being unpatentable under 35 USC 103(a) have been fully considered but they are not persuasive for the following reasons.
In response to Applicant’s first argument, i.e., an ordinary skilled artisan would not have a reasonable expectation of success in arriving at the claimed invention, particularly in view of the unpredictable nature of cholesterol modification and linker optimization, and thus, the cited art do not enable a person skilled in the art to arrive at the present invention, it is found unpersuasive. It is acknowledged that there is not a single reference that teaches and/or suggests every claim limitation recited in instant claim 7 and the dependent claims. However, Applicants are respectfully reminded that the rejection supra is based on obviousness. Pursuant to MPEP 2142, 35 USC 103 authorizes a rejection where, to meet the claim, it is necessary to modify a single reference or to combine it with one or more other references (emphasis added). Since the rejection is based on obviousness, it is unnecessary for every claim limitation to be taught and/or suggested by a single reference. Since the rejection is based on obviousness, it is unnecessary for every claim limitation to be taught and/or suggested by a single reference. Additionally, the Examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, as discussed above in the 103 rejection, the teachings of ‘008 and Mathieu et al. are suggestive of the claim limitations as recited in instant claims 7 and 14-22. ‘008 teaches instant SEQ ID NO: 2 thereby constituting a polypeptide as recited in claim 7(1) that is modified via a flexible GSGG linker to a cell-penetrating peptide where this modified polypeptide exhibits inhibitory activity against a coronavirus. As such, the question is whether an ordinary skilled artisan would be motivated with a reasonable expectation of success to substitute the cell-penetrating peptide of ‘008’s modified polypeptide with a palmitoyl group or a cholesterol group. Notably, the scope of claim 7 does not require any linker in order to conjugate the EK1 polypeptide to the lipid group thereby encompassing the GSGG linker taught by ‘008. Thus, the Examiner maintains that the answer to this question is yes in light of the teachings of Mathieu et al. suggesting that cholesterol conjugation to an inhibitory viral polypeptide via a GSGSG-PEG4 flexible linker resulted in improved efficacy against coronavirus infection and improved stability against enzymatic degradation. Therefore, the Examiner maintains that the claimed invention is rendered prima facie obvious in light of the combined teachings of ‘008 and Mathieu et al.
Regarding whether an ordinary skilled artisan would have a reasonable expectation of success, pursuant to MPEP 2143.02(II), obviousness does not require absolute predictability, however, at least some degree of predictability is required. Evidence showing there was no reasonable expectation of success may support a conclusion of nonobviousness. In re Rinehart, 531 F.2d 1048, 189 USPQ 143 (CCPA 1976). In the instant case, it is acknowledged that Mathieu et al. does not teach an inhibitory polypeptide sequence that is encompassed by the scope of instant claim 7. It is further noted that Mathieu et al. does not teach an inhibitory polypeptide that exhibits activity against a coronavirus. Notwithstanding that the rejection is one of obviousness and not anticipation, and thus, the fact that Mathieu et al. alone does not teach every claim limitation does not per se preclude a finding of obviousness as discussed supra, the rejection further relies on the teachings of the references demonstrating that coronavirus and paramyxovirus (i.e., reduced to practice by Mathieu) utilize a similar mechanism to mediate virus-cell fusion and subsequent viral entry. More specifically, ‘008 teaches that the EK1 polypeptide inhibits coronaviral cell entry by binding to the HR1 region of the S2 protein thereby interfering with the virus’s own six-helix formation, which is similar to the lipopeptide fusion inhibitors of Mathieu et al. that were known to interfere with the initial step of viral entry by blocking formation of the 6-helix bundle. Applicant arguing that the two viruses differ completely constitutes the argument of counsel and is unsupported by evidence or declarations of those skilled in the art. Attorney argument is not evidence unless it is an admission, in which case, an examiner may use the admission in making a rejection. See M.P.E.P. § 2129 and § 2144.03 for a discussion of admissions as prior art. Counsel's arguments cannot take the place of objective evidence. In re Schulze, 145 USPQ 716 (CCPA 1965); In re Cole, 140 USPQ 230 (CCPA 1964); and especially In re Langer, 183 USPQ 288 (CCPA 1974). See M.P.E.P. § 716.01(c) for examples of attorney statements that are not evidence and that must be supported by an appropriate affidavit or declaration. Although the Examiner is not contending the two viruses are identical or related, the combination of ‘008 and Mathieu et al. suggest that the viral entry mechanisms are similar. Therefore, contrary to Applicant’s argument, an ordinary skilled artisan would have the requisite expectation of success in substituting the GSGG-CPP component of ‘008’s inhibitory polypeptide with the GSGSG-PEG4-cholesterol suggested by Mathieu et al.
Furthermore, regarding whether Mathieu et al. is enabled, pursuant to MPEP 2152.02(b), in order for a prior art document to describe a claimed invention under AIA 35 U.S.C. 102(a)(1) or (a)(2), the prior art document need only describe and enable one skilled in the art to make a single species or embodiment of the claimed invention. See Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1562, 19 USPQ2d 1111, 1115 (Fed. Cir. 1991). In the instant case, although Mathieu et al. does not reduce-to-practice an inhibitory polypeptide against a coronavirus or demonstrate improved efficacy and/or stability when cholesterol is conjugated to an inhibitory polypeptide against a coronavirus does not per se render the teachings Mathieu et al. as not enabled. Notably, Mathieu et al. does not expressly identify that the improved efficacy and/or stability when cholesterol is conjugated to an inhibitory polypeptide against paramyxovirus is limited in scope. In fact, as discussed in the rejection supra, Mathieu et al. expressly suggests that the cholesterol conjugation strategy found to be beneficial against paramyxovirus could be useful against other viruses. More specifically, Mathieu et al. expressly teaches that the cholesterol conjugation method can be broadly applied to other inhibitory viral polypeptides given that the majority of fusion proteins that mediate enveloped viral entry have molecular regions that interact to mediate virus-cell fusion that can be identified from the primary sequence, and lipopeptide fusion inhibitors can be designed on the basis of pathogen genetic information. As discussed supra, the ‘008 inhibitory polypeptide inhibits coronavirus via a similar mechanism when compared to the inhibitory polypeptide of Mathieu et al. against paramyxovirus. Thus, contrary to Applicant’s argument, a reference does not require an actual reduction-to-practice in order for a reference to be considered enabled. Therefore, the Mathieu et al. is enabled for what it teaches and suggests; that is, utilizing the cholesterol conjugation method to improve efficacy and/or stability of inhibitory viral polypeptides.
Additionally, regarding enhanced activity following cholesterol modification being unpredictability, although it is acknowledged that Mathieu et al. suggests improved inhibitory activity when cholesterol is conjugated to an inhibitory viral polypeptide, it is not the only advantage suggested by Mathieu et al. As discussed in the rejection supra, the cholesterol conjugation method suggested by Mathieu et al. also improved stability by reducing protease degradation of the polypeptide. Pursuant to MPEP 2144, a difference in objectives, if any, does not defeat the case for obviousness because the “reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. In re Linter, 458 F.2d 1013, 173 USPQ 560 (CCPA 1972) …; In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990), cert. denied, 500 U.S. 904 (1991) … .” As such, even assuming arguendo that an ordinary skilled artisan would not have a reasonable expectation of success to enhance anti-coronavirus activity, an ordinary skilled artisan would have the requisite expectation of success to improve the stability of the EK1 polypeptide taught by ‘008. Applicants have not provided any evidence to suggest that improved polypeptide stability is not a reasonable expectation. Applicants are respectfully reminded that the claim invention is directed to a product and not a method of using the product. Therefore, an ordinary skilled artisan is not limited to have a reasonable expectation of success to modify ‘008’s polypeptide with the cholesterol conjugation method of Mathieu et al. in order to enhance inhibitory activity against a coronavirus.
Regarding the linkers, it is noted that the features upon which applicant relies (i.e., the linker between the EK1 polypeptide and lipid modification) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). In the instant case, as discussed supra, the scope of claim 7 does not require any linker between the EK1 polypeptide and lipid modification. Examiner stipulates that if the linker is critical to achieving the desired inhibitory activity against a coronavirus as Applicant appears to be asserting, i.e., the GSGSG-PEG4 in this application was specifically designed and optimized in the context of the EK1 peptide to enhance its anti-coronavirus activity (See Applicant’s Response received on 11/18/25, pg. 14), then the linker should be recited in the independent claim. As discussed in response to Applicant’s second argument below, unexpected results must be commensurate in scope. Therefore, if the linker is critical to achieving unexpected enhanced anti-coronavirus activity, such a limitation is required to be recited in the independent claim.
In response to Applicant’s second argument, i.e., the claimed invention exhibits unexpected results of enhanced inhibitory activity against a coronavirus as demonstrated in Table 5, it is found unpersuasive. Pursuant to MPEP 716.02(d), whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the “objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.” See MPEP 716.02(d). In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. See MPEP 716.02(d). In the instant case, it is acknowledged that the specific EK1 polypeptide derivatives containing SEQ ID NO: 2 conjugated to palmitic acid or cholesterol via a GSGSG-PEG4 linker at the C-terminus of the polypeptide sequence exhibited significantly enhanced inhibitory activity against several coronaviruses (See instant Table 5 and Figures 3-6). Moreover, as pointed out by Applicant, “[t]he linker –(GSGSG)n-PEG4- in this application was specifically designed and optimized in the context of the EK1 peptide to enhance its anti-coronavirus activity” (See Applicant’s Response received on 11/18/25, pg. 14). Furthermore, Applicant states that the specific polypeptide derivative of SEQ ID NO: 14 in the inventors’ post filing reference exhibits superior inhibitory activity against coronaviruses (See Applicant’s Response received on 11/18/25, pg. 15). Applicant concludes that the Xia reference “proves that the claimed EK1 polypeptide derivative having the particular PEGylated linker achieves unexpected technical effects in inhibiting coronaviruses” (See Applicant’s Response received on 11/18/25, pg. 15). Thus, the data provided in the instant specification and as stated by Applicant’s in their Response demonstrate that the unexpected results are dependent upon specific polypeptide derivatives with a specific amino acid sequence, i.e., SEQ ID NO: 2, conjugated to palmitic acid or cholesterol via a –(GSGSG)n-PEG4-. Therefore, the structure of the polypeptide derivatives that exhibit the unexpected results must be recited in claim 7 in order to be commensurate in scope with the unexpected results.
Additionally, it is noted that the Federal Circuit found, “[t]o be particularly probative, evidence of unexpected results must establish that there is a difference between the results obtained and those of the closest prior art, and that the difference would not have been expected by one of ordinary skill in the art at the time of the invention.” Bristol-Myers Squibb Co. v. Teva Pharms. USA, Inc., 752 F.3d 967, 977 (Fed. Cir. 2014). MPEP 716.02(b) states that evidence of unexpected properties may be in the form of a direct or indirect comparison of the claimed invention with the closest prior art which is commensurate in scope with the claims. See In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980) and MPEP § 716.02(d) - § 716.02(e). See In re Blondel, 499 F.2d 1311, 1317, 182 USPQ 294, 298 (CCPA 1974) and In re Fouche, 439 F.2d 1237, 1241-42, 169 USPQ 429, 433 (CCPA 1971) for examples of cases where indirect comparative testing was found sufficient to rebut a prima facie case of obviousness. In the instant case, the closest prior art is the ‘008 reference. As discussed in the rejection supra, the ‘008 reference teaches a fusion protein comprising SEQ ID NO: 2 fused to a CPP peptide via a GSGG flexible linker. As such, Applicant need to compare the closest prior art product, i.e., ‘008’s EK1 polypeptide derivative, with the claimed EK1 polypeptide derivative in order to demonstrate unexpected results.
Accordingly, the rejection of claim 7 and 14-22 is maintained as Applicants’ arguments are found unpersuasive.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, 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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/THEA D' AMBROSIO/Primary Examiner, Art Unit 1654