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 .
Claim Status
Claims 57 and 64-76 are pending. Claims 58-63 were canceled in the Reply filed 5/12/2026. No new claims were added. Claim 57 was amended. Claims 57 and 64-76 are presently considered.
Election/Restriction
The claims are directed to products or methods requiring a composition comprising two peptides comprising SEQ ID NO: 1, two PEG moieties of unspecified size, and one cholesterol tag. Accordingly, an election/restriction requirement has not been set forth on record at this time. However, Applicant is directed to MPEP §§ 818, 818.02(a), 819, and 821.
A single species of compound and a single species of in vivo administration were reduced to practice (see, e.g., Example 8 at ¶¶[0179]-[0181], instant Figures 11A and 26).
Claims 57 and 64-76 are presently considered.
Priority
The priority claim to US Provisional Application 63/091915 (filed 10/14/2020) is acknowledged, but differs from the instant Specification filed 4/13/2023.
Information Disclosure Statement
The IDS filed 2/02/2026 and 5/12/2026 are each acknowledged and presently considered.
Applicant should note that one or more documents disclosed on the IDS form submitted on 2/02/2026 (9 pages) were not considered since they did not conform to 37 CFR 1.98(b) by providing a proper date, as 37 CFR 1.98(b) requires that each publication must be identified by publisher, author (if any), title, relevant pages of the publication, and date and place of publication. The date of publication supplied must include at least the month and year of publication, except that the year of publication (without the month) will be accepted if the applicant points out in the information disclosure statement that the year of publication is sufficiently earlier than the effective U.S. filing date and any foreign priority date so that the particular month of publication is not in issue. See MPEP 609.04(a). Here, the earliest priority claim is to US Provisional Application 63/091915, filed 10/14/2020; therefore, all documents published in 2019 or later must be accompanied by both month and date of publication.
References that were not considered have been indicated by strike-though on the attached IDS forms. Although not considered, these documents have been placed in the application file, but the information referred to therein has not been considered as to the merits. Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a).
Claim Interpretation
For purposes of examination, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action. Applicant is advised that a specialized definition should be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer).
Amended claim 57 is representative of the pending claim scope. Applicable claim interpretations are set forth below.
Amended claim 57 recites “having”. Per MPEP § 2111.03(IV), “having” may be interpreted as open language equivalent to comprising. “Comprising” is an open-ended transitional term (see, e.g., MPEP § 2111.03(I)), wherein additional steps or components are not excluded. However, “‘[c]omprising’ is a term of art used in claim language which means that the named elements are essential” (see, e.g., id.; see also Genentech, Inc. v. Chiron Corp., 112 F.3d 495, 501, 42 USPQ2d 1608, 1613 (Fed. Cir. 1997)).
Instant SEQ ID NO: 1 has the following sequence:
DISGINASVVNIQKEIDRLNEVAKNLNESLIDLQEL
Accordingly, instant SEQ ID NO: 1 is understood to be a prior art element, namely SEQ ID NO: 48 of WO2005/077103 (see, e.g., WO’103 at SEQ ID NO: 48).
Instant SEQ ID NO: 5 has the following sequence:
DISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGSGSGC
Accordingly, SEQ ID NO: 5 only differs from instant SEQ ID NO: 1 by the presence of the sequence of GSGSGC (i.e., instant SEQ ID NO: 13).
SEQ ID NO: 7 is identical to SEQ ID NO: 5, except that it lacks the C-terminal Cys residue:
DISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGSGSG
However, amended claim 57 continues to recite a “peptide” + cysteine residue linker, and therefore claim 57 is understood to continue reading upon SEQ ID NO: 5, as previously examined.
Claim 65 recites “preventing COVID-19”. In this context, an artisan would readily appreciate that “preventing COVID-19” does not refer to prevention of SARS-CoV-2 virions entering the human body (e.g., by breathing, which would raise enablement issues under 35 USC 112(a)), but instead refers to the prevention of COVID-19 infection specifically caused by cell entry of SARS-CoV-2 virions by fusing with a cell receptor, wherein inhibiting fusion nu binding to a viral spike protein prevents its function and transmission (see, e.g., Spec. filed 4/13/2023 at ¶¶[0029], [0034], [0055], [0061]-[0062], [0081], [0087], [0088], [0129], [0179]-[0181], Figs. 3, 10A-B, 21A-J).
Additional claim interpretations are set forth below.
Withdrawn Claim Rejections
The rejection of claims 61-62 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite, is withdrawn as moot in view of the cancellation of claims 61-62.
The rejection of claims 57-76 under 35 U.S.C. 103 as being unpatentable over WO2005/077103 in view of Pessi et al.1 is withdrawn in part in view of the amendments to claim 57 and cancellation of claims 58-63. A revised rejection is set forth below.
Revised Claim Rejections as Necessitated by Applicant Amendment
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 57 and 64-76 are rejected under 35 U.S.C. 103 as being unpatentable over WO2005/077103 in view of Pessi et al.2.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding and separate section above, and those discussions and interpretations are incorporated into the instant rejection. Instant claims 57 and 64-76 are understood to read upon at least compounds (and methods of using compounds) comprising [(SEQ ID NO:1)-GSGSG-C-(MAL-PEG4-NH2]2-Cholesterol], which may be alternatively written as [(SEQ ID NO:5)-(MAL-PEG4-NH2]2-Cholesterol], or [(SEQ ID NO:7)-C-(MAL-PEG4-NH2]2-Cholesterol]. Additional claim interpretations are set forth below.
Regarding instant claims 57 and 64-76, instant SEQ ID NO: 1, and methods of administering instant SEQ ID NO: 1 to patients for the treatment of SARS coronavirus injection, WO’103 identifies that instant SEQ ID NO: 1 is a prior art element, namely an “HR-C4a extended (1150-1185)” (i.e., “HR” is heptad repeat) (see, e.g., WO’103 at Table at ¶[0053]), which is art-recognized as a peptide of SARS coronavirus capable of modifying SARS coronavirus infectivity and usable in methods of treating SARS coronavirus infection in subjects (see, e.g., WO’103 at SEQ ID NO: 483, claims 1, 5, 84, 30, and 37; compare id. with instant SEQ ID NO: 1, showing 100% sequence identity). Accordingly, instant SEQ ID NO: 1 is a prior art element that was explicitly taught for use in methods of treating and preventing SARS by inhibiting a coronavirus from achieving fusion and entry into a target cell (see, e.g., WO’103 at abs, ¶¶[0004]-[005], [0016], [0028]-[0029], [0045]-[0046], [0051], SEQ ID NO: 48, claims 1, 5, 8, 30, 33, 35, and 37). Regarding amended claim 57 and acetylation at the N-terminus of SEQ ID NO: 1, WO’103 explicitly teaches, discloses, and directs artisans to N-terminally acetylate the disclosed peptides (see, e.g., WO’103 at ¶[0097]; see also WO’103 at ¶[0175]). Accordingly, an artisan following the guidance of WO’103 would have N-terminal acetylated such peptides consistent with the WO’103 disclosure. Regarding instant claims 65-76 and administration of effective dosages, WO’103 identifies that effective dosages may be determined using routine methods, and that “about 10 ng per mL” of a peptide would be reasonably included (see, e.g., WO’103 at ¶[0211]). Regarding instant claim 65-76 and general methods of administration to treat a coronavirus infection, instant SEQ ID NO: 1 is a prior art element that was explicitly taught for use in methods of treating and preventing SARS by inhibiting a coronavirus from achieving fusion and entry into a target cell (see, e.g., WO’103 at abs, ¶¶[0004]-[005], [0016], [0028]-[0029], [0045]-[0046], [0051], SEQ ID NO: 48, claims 1, 5, 8, 30, and 37). Accordingly, an artisan would readily appreciate that the HR sequence of SEQ ID NO: 48 of WO’103 could be administered to subjects in need to desirably treat and prevent SARS (see, e.g., WO’103 at claims 1, 5, 8, 30, 33, 35, and 37). Regarding instant claims 64, 70-73, and intranasal and respiratory administration using a suitable pharmaceutical formulation, explicitly teaches that the disclosed peptides may be formulated with excipients suitable for intranasal or respiratory routes of administration, including nebulization formulas or atomization spray formulas (see, e.g., WO’103 at ¶¶[0196], [0210], [0212]). Regarding instant claim 76 and administration prior to exposure, WO’103 identifies that the disclosed sequences are for use as vaccines, and can be used to treat or prevent infection (see, e.g., WO’103 at title, ¶¶[0046], [0161], [0189], claims 1, 5, 8, 30, 33, 35, and 37), and therefore an artisan would readily appreciate that they could advantageously be delivered prior to exposure to predictably reduce risk of infection. In sum, a composition comprising the prior art substance of SEQ ID NO: 48 would be predicted and expected to treat coronavirus infection and to prevent and inhibit a coronavirus from achieving fusion and entry into a target cell exactly as taught, disclosed, and claimed by the prior art.
The primary reference differs from the instant claim scope as follows: The primary reference does not teach the modification of the HR peptide SEQ ID NO: 48 as disclosed by WO’103, as required to form a structure comprising two copies of the peptide, two PEG moieties, and one cholesterol tag as instantly claimed.
Regarding instant claims 57, 64-76, and methods of preventing a virus from achieving fusion and entry into a target cell, Pessi discloses a “general strategy” for improving the potency of an antiviral peptide, namely by dimerization and attaching an N-terminally acetylated peptide to a cholesterol group, wherein such attachment desirably and predictably increases antiviral potency and improves half-life in vivo (see, e.g., Pessi at title, abs, Fig. 1 on 3, 2 at col II, Table 1 at HPIV-P4). Specifically, Pessi directs artisans to conjugate antiviral peptides as shown at Figure 1, reproduced below:
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(see, e.g., Pessi at Fig. 1 on 3). This construct is exemplified by the disclosure of [(sequence)-GSGSG-C-(MAL-PEG4)]2-Chol] at Table 1 (see, e.g., Pessi at Table 1 at HPIV-P4). Regarding the construct at amended claim 57 (e.g., instant Figure 11A), the compounds taught, suggested, and exemplified by Pessi appear to be highly similar to the compound shown at instant Figure 11A (compare instant Figure 11A with Pessi at Fig. 1 on 3, 2 at col II, Table 1 at HPIV-P4, noting that both structures comprising the linking sequence of “GSGSGC”, maleimide derivatives, PEG4, a cholesterol moiety, and a trimeric branching core). The only differences appear to be (i) the HR antiviral sequence utilized, (ii) the -CH2- repeats between the maleimide derivative and the PEG4 moieties, and that (iii) Pessi does not show the stereochemistry of cholesterol. However, with respect to (ii)-(iii), a difference in -CH2- repeats and stereochemistry is obvious (see, e.g., MPEP § 2144.09(I)-(II), noting that a prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities, and here the utilities are identical, and the compounds are homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups), and therefore generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious)). In addition, the stereochemistry of cholesterol would be understood because cholesterol is a routine compound in the chemical arts. Regarding instant SEQ ID NO: 5 and SEQ ID NO: 7, instant SEQ ID NO: 5 is identical to instant SEQ ID NO: 1, except for the presence of the C-terminal linker of GSGSGC present in SEQ ID NO: 5; similarly, instant SEQ ID NO: 7 is identical to instant SEQ ID NO: 1 except for the presence of the C-terminal linker of GSGSG present in SEQ ID NO: 7. Furthermore, the only difference between SEQ ID NO: 5 and SEQ ID NO: 7 is that SEQ ID NO: 7 does not include the C-terminal Cys present in SEQ ID NO: 5, but this Cys is not “missing”, but instead merely written separately from the rest of the polypeptide portion in the structure of amended claim 57. However, these differences are all encompassed by the exemplified embodiment of Pessi, because Pessi discloses and exemplifies the usage of the linker of GSGSGC, which is a prior art element and taught explicitly for use in the dimeric, cholesterol linked structures taught and disclosed by Pessi (see, e.g., Pessi at Fig. 1 on 3, 2 at col II, Table 1 at HPIV-P4, showing a “GSGSGC” linker). Accordingly, by simply substituting SEQ ID NO: 48 of the primary reference into the exemplified embodiment of Pessi yields SEQ ID NO: 5 and 7. Accordingly, the addition of a known linker to a known peptide in a known arrangement does not weigh in favor of allowability. Regarding instant claims 74-75 and repeated administration, instant claims 74-75 only differ from the guidance of the prior art with respect to the frequency of dosage, and amount to a requirement to repeat the prior art process to treat or prevent infection (see, e.g., WO’103 at title, ¶¶[0046], [0161], [0189], claims 1, 5, 8, 30, 33, 35, and 37). The simple repetition of a known step to achieve an art-recognized outcome is “merely the logical result of common sense application of the maxim ‘try, try again’” (see, e.g., Perfect Web Technologies, Inc. v. InfoUSA, Inc. 587 F.3d 1324 (Fed. Cir. Dec. 2, 2009)). In the instant case, an artisan would understand that repeating the prior art methodology, would predictably lead to the obvious result of higher levels of peptides capable of inhibiting or preventing infection, and therefore readily appreciate that such steps could be repeated to logically achieve a desired outcome. In addition, Pessi identifies and exemplifies that related substances (dimeric peptides conjugated to cholesterol via PEG4 moieties) may be administered to subjects every day, repeatedly for up to 14 days (see, e.g., Pessi at 6 at col I at 1st full ¶).
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s):
First, the invention is the combination of prior art elements (i.e., the peptide of WO’103 with the dimeric, PEG4 containing cholesterol structure of Pessi) according to known methods of modifying and improving viral HR peptides as taught by Pessi and according to known methods of treating and preventing SARS coronavirus as taught by WO’103, wherein such methods would predictably and expectedly result in
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wherein “R” is Ac-DISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGSGSGC, and wherein such structure would have the same utility and applicability to treatment and prevention methods as taught by the primary reference, but wherein the modified structure would predictably exhibit improved potency and half-life as taught and disclosed by Pessi (see, e.g., MPEP §§ 2143(I)(A), (G), 2144.09(I)). Furthermore, each prior art element would merely performs its art-recognized function in combination as it does alone.
Second, or alternatively, the invention is the simple substitution of the HR peptide of the primary reference in place of the HR peptide shown in the HPIV-P4 compound of the secondary reference, wherein such substitution would predictably and expectedly result in
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wherein “R” is Ac-DISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGSGSGC, and wherein such structure would have the same utility and applicability to treatment and prevention methods as taught by the primary reference, but wherein the modified structure would predictably exhibit improved potency and half-life as taught and disclosed by Pessi (see, e.g., MPEP §§ 2143(I)(B), (G), 2144.09(I)).
Third, or alternatively, the claimed invention is the simple application or use of the known technique of using dimeric, branched PEG conjugated to cholesterol to improve HR antiviral polypeptides in the manner taught by the secondary reference to the product (and related methods of treating coronavirus) as taught by the primary reference, wherein such improvement would predictably yield compounds of form
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wherein “R” is Ac-DISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGSGSGC, and wherein such structure would have the same utility and applicability to treatment and prevention methods as taught by the primary reference, but wherein the modified structure would be improved by having improved potency and half-life as taught and disclosed by Pessi (see, e.g., MPEP §§ 2143(I)(C)-(D), (G), 2144.09(I)).
Accordingly, the claimed invention is obvious in view of the prior art.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to improve a known compound having known applications, in a known manner explicitly taught by the prior art, to predictably obtain the exact results taught and suggested by the prior art.
Accordingly, claims 57-76 are rejected.
Response to Arguments
Applicant’s arguments filed 5/12/2026 have been fully considered, but multiple arguments have been rendered moot in view of withdrawn or revised rejections as set forth above. Applicant raises arguments pertaining to the revised rejection under 35 USC 103 at pages 7-10 of the Reply (see, e.g., Reply filed 5/12/2026 at 7 at 1st ¶ to 10 at 2nd full ¶), which are addressed below.
Applicant alleges that a determination of obviousness of a chemical compound requires that “the Office must identify a lead compound” (see, e.g., Reply filed 5/12/2026 at 7 at 1st ¶ to final ¶). This is factually and legally incorrect because MPEP 2143(I) literally states
It should be noted that the lead compound cases do not stand for the proposition that identification of a single lead compound is necessary in every obviousness rejection of a chemical compound.
(see, e.g., MPEP § 2143(I)(B), Example 10, emphasis added)
In direct contrast to the Applicant’s statements, exemplary rationales for establishing obviousness include the rationales set forth at MPEP §§ 2143(I)(A)-(G), 2144(I)-(III), 2144.04, 2144.05(I), 2144.05(II), 2144.06(I), 2144.06(II), 2144.07, 2144.08, 2144.09, etc. In fact, examples of rationales supporting determinations of obviousness without a lead compound analysis are explicitly addressed in the MPEP:
For example, one might envision a suggestion in the prior art to formulate a compound having certain structurally defined moieties, or moieties with certain properties. If a person of ordinary skill would have known how to synthesize such a compound, and the structural and/or functional result could reasonably have been predicted, then a prima facie case of obviousness of the claimed chemical compound might exist even without identification of a particular lead compound.
(see, e.g., MPEP § 2143(I)(B), Example 10, emphasis added)
As a second example, it could be possible to view a claimed compound as consisting of two known compounds attached via a chemical linker. The claimed compound might properly be found to have been obvious if there would have been a reason to link the two, if one of ordinary skill would have known how to do so, and if the resulting compound would have been the predictable result of the linkage procedure. Thus, Office personnel should recognize that in certain situations, it may be proper to reject a claimed chemical compound as obvious even without identifying a single lead compound.
(see, e.g., MPEP § 2143(I)(B), Example 10, emphasis added)
Therefore, all arguments premised upon assertions regarding a non-existent legal requirement that a lead compound analysis must be used and is required to establish obviousness are not persuasive because the underlying premise is incorrect (see, e.g., Reply filed 5/12/2026 at 7 at 1st ¶ to 9 at 2nd full ¶).
It is the Examiner’s understanding that Applicant is characterizing the “lead compound” analysis as requiring that the Office must identify a single compound, namely “a compound in the prior art that would be most promising to modify” (see, e.g., Reply filed 5/12/2026 at 7 at penultimate ¶). It is the Examiner’s understanding that Applicant is suggesting that the “lead compound” analysis requires identification of a “single lead compound” (see id). This is not persuasive, because the courts have previously addressed and dismissed such assertions as inconsistent with KSR:
In response to Altana’s argument that the prior art must point to only a single lead compound for further development, the Federal Circuit stated that a "restrictive view of the lead compound test would present a rigid test similar to the teaching-suggestion-motivation test that the Supreme Court explicitly rejected in KSR . . . .
(see, e.g., MPEP § 2143(I)(B), Example 10, emphasis added).
Therefore, all arguments premised upon assertions regarding a non-existent legal requirement are not persuasive because the underlying premise is incorrect (see, e.g., Reply filed 5/12/2026 at 7 at penultimate ¶).
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references (see, e.g., Reply filed 5/12/2026 at 7 at 1st ¶ to 9 at 2nd full ¶), 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, the Examiner provided multiple rationales supporting a determination of obviousness, including rationales under MPEP §§ 2143(I)(A), (B), (C), (D), (G), and 2144.09(I). Applicant fails to identify any factor required by these rationales, which was not addressed in the rejection of record, which means that multiple rationales supporting a determination of obviousness are not disputed on the instant record with specificity.
It is the Examiner’s understanding that Applicant alleges that there was no rationale to select SEQ ID NO: 48 of WO’103 in view of the “numerous peptides other than SEQ ID NO:48” that were disclosed (see, e.g., Reply filed 5/12/2026 at 8 at 1st ¶ to 3rd full ¶). First, this line of arguments is not credible because the rejection explicitly directs Applicant to multiple citations in the rejection supporting the selection of SEQ ID NO: 48; for example, the rejection cites WO’103 at claims 8 and 33, wherein SEQ ID NO: 48 was only one of two explicitly enumerated peptides. It is not reasonable or credible to ignore such prior art guidance, and “two” is not reasonably identifiable as “numerous peptides”. Second, the rejection explains the selection of SEQ ID NO: 48, namely it is an antiviral peptide suitable for treating coronavirus (e.g., Rejection, above). The courts have long stated that "[r]eading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle." (see, e.g., Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327 (1945), at 335). Accordingly, the selection of a known, prior art peptide explicitly taught in the prior art for use as an antiviral peptide suitable for treating coronavirus, for use for that exact purpose, is obvious (see id). Third, the Court has stated that
"[W]hen a patent 'simply arranges old elements with each performing the same function it had been known to perform' and yields no more than one would expect from such an arrangement, the combination is obvious."
KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 , 417 , 127 S. Ct. 1727 , 167 L. Ed. 2d 705 (2007) (quoting Sakraida v. Ag Pro, Inc., 425 U.S. 273 , 282 , 96 S. Ct. 1532 , 47 L. Ed. 2d 784 (1976)).
Likewise, the Supreme Court has rejected rigid tests for obviousness and has emphasized that
[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.”
KSR Int'l v. Teleflex Inc., 550 U.S. 398, 415 (2007), at 416.
And has also emphasized that
“If a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability.”
KSR Int'l v. Teleflex Inc., 550 U.S. 398, 415 (2007), at 417.
Here, as explained by the rejection, the claimed invention is the combination of two prior art components, namely a known antiviral peptide taught by WO’103 and a known structure capable of being conjugated to antiviral peptides that would improve the potency of the antiviral peptide. Accordingly, no novel structures or unexpected results or properties have been identified on record, but instead, exactly as stated in the rejection of record, “each prior art element would merely performs its art-recognized function in combination as it does alone” (see rejection revised above; see also Rejection under 103 of record). In sum, arguments amounting to a dismissal of the Examiner’s rationales supporting a determination of obviousness of record are not persuasive.
It is the Examiner’s understanding that Applicant alleges that the prior art “does not appear to disclose any data for SEQ ID NO: 48” (see, e.g., Reply filed 5/12/2026 at 8 at 3rd full ¶ to 4th full ¶). Actual reduction to practice is not required to support a determination of obviousness in view of express disclosures in the prior art because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), and also a “reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art” (see, e.g., MPEP § 2123(I)).. If Applicant means to suggest that the prior art is not fully enabled or operable (see, e.g., Reply filed 5/12/2026 at 8 at 3rd full ¶ to 4th full ¶), Applicant is directed to MPEP § 2121(I), which notes that the prior art is presumed fully enabled for all that it discloses, and the burden is on the Applicant to rebut the presumption of operability (see, e.g., MPEP § 2121(I); MPEP § 716.07). No evidence of inoperability commensurate in scope with the requirements of MPEP § 716.07 have been placed on record at this time; critically, arguments of counsel cannot take the place of evidence in the record (see, e.g., In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965), and evidence is required to rebut the presumption of operability. The Examiner’s position is that the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), including “all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments” (see, e.g., MPEP § 2123(I)). Accordingly, the Applicant has not satisfied their burden to rebut the presumption of operability of the prior art at this time (see, e.g., MPEP § 2121(I); MPEP § 716.07). If Applicant means to suggest that in the absence of data, the prior art statements would be met with skepticism of experts (see, e.g., Reply filed 5/12/2026 at 8 at 3rd full ¶ to 4th full ¶), Applicant is directed to MPEP § 716.05, which explains that supporting evidence should be filed per MPEP § 716.05 as evidence is required to establish skepticism of experts. In the absence of such evidence, such statements are understood to be unsupported conjecture of counsel. The prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), including “all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments” (see, e.g., MPEP § 2123(I)), and no objective evidence rebutting this presumption has been placed on record to date. In sum, SEQ ID NO: 48 is presumed fully enabled for use as an antiviral peptide suitable for use in the treatment of coronavirus, exactly as taught and disclosed by the prior art.
It is the Examiner’s understanding that Applicant alleges that the Examiner relied upon improper hindsight bias reasoning (see, e.g., Reply filed 5/12/2026 at 8 at 4th full ¶, 9 at 1st full ¶ to 2nd full ¶). In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Here, Applicant identifies zero structures, methods, or steps “gleaned only from the applicant’s disclosure”. Rather, the rejection clearly establishes that all aspects of the claimed invention (e.g., all structures, parameters, and expected and predicted functionalities) were already known in the prior art, and the art identifies the “general strategy” and motivation for making such combinations, along with the predicted and expected results as identified in the rejection. Therefore, the combination of only known components according to known arrangements and methods, to only yield the predicted and expected results explicitly taught by the prior art, does not support a determination of improper hindsight.
Allegations suggesting “lack of predictability” or “lack of reasonable expectation of success”: It is the Examiner’s understanding that Applicant is alleging that there is a lack of reasonable expectation of successfully utilizing the “general strategy” of Pessi because Pessi utilizes hedging language like “may” (e.g., “may be a general strategy”, “may be compatible”, “antiviral potency may be increased”, etc.) (see, e.g., Reply filed 5/12/2026 at 8-9 at bridging ¶). This is not persuasive because the Applicant’s assertions do not reflect the proper legal standards for evaluating predictability. MPEP § 2143.02(II) explains that “[o]bviousness does not require absolute predictability”, but instead clarifies that only “at least some degree of predictability is required” (see, e.g., MPEP § 2143.02(II)). Here, the rejection explicitly addresses predictability and reasonable expectation of success, but Applicant fails to address the explicitly identified predicted and expected results set forth in the rejection. Here, the Examiner’s basis for “predictability” is merely based upon the presumption that the prior art is fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). As explained at MPEP § 2143.02, predictability and reasonable expectation of success are satisfied when “all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art”. Here zero evidence of unexpected results commensurate in scope with the requirements of MPEP 716.02 have been set forth on record, all elements of the claimed invention were known in the prior art, one of ordinary skill was fully enabled to combined each component using routine methods in the biochemical arts per the guidance of the primary reference, and the elements would have merely performed their art-recognized, respective functions (see Rejection, above). Furthermore, it is routine in the academic arts to use cautious or hedging language to reasonably represent that conclusions are based upon limited data and acknowledge the potential existence of exceptions not yet discovered. Accordingly, a reasonable artisan would simply weigh the evidence and teachings shown by Pessi, and would readily note that zero evidence of any exceptions contradicting such conclusions are provided in Pessi, and therefore, such hedging language would be seen only as an academic precaution rather than as a precaution based upon scientific and statistically significant evidence. Accordingly, as explained above, “at least some degree of predictability” exists, and therefore an artisan would have a reasonable expectation that the teachings and structures of Pessi could be utilized advantageously as a “general strategy” to enhance the antiviral potency of art-recognized antiviral peptides, such as SEQ ID NO: 48 of the primary reference.
It is the Examiner’s understanding that Applicant refers to a “universe of potential options to explore” and refers to the Federal Circuit statement regarding the rationale of MPEP § 2143(I)(E) (i.e., “obvious to try” rationale) (see, e.g., Reply filed 5/12/2026 at 8-9 at bridging ¶). First, the rejection does not recite nor depend upon the rationale at MPEP § 2143(I)(E), and therefore Applicant’s apparent suggestion to the contrary is incorrect. The rejection is based upon the rationales recited in the rejection, namely MPEP §§ 2143(I)(A), (B), (C), (D), (G), and 2144.09(I); however, Applicant fails to identify any factor required by these rationales, which was not addressed in the rejection of record. Second, the reliance upon Grunenthal v.[sic] GmbH v. Alkem Labs. Ltd., 919 F.3d 1333 is misplaced because in the instant Application, the rejection cites WO’103 at claims 8 and 33, wherein SEQ ID NO: 48 was only one of two explicitly enumerated peptides, and Pessi discloses only four structures, wherein the P3 and P4 were repeatedly shown to be the most potent (see, e.g., Pessi at Table 1 on 4, Fig. 2 on 4, Fig. 3 on 5, Fig. 4 on 5 , Fig. 5 on 6). Conjugating two known antiviral peptides to two known potency enhancing structures known in the art is four possibilities, which all would be expected and predicted to merely yield the results taught in the prior art. Such few possibilities, representing only one chemical modification (i.e., conjugation of the potency-enhancing scaffold to the prior art antiviral peptide) does not reasonably or credibly represent a “universe of potential options to explore”, but rather a known modification to a known peptide, wherein the known modification improves the known peptide in a known an predictable manner. Third, the Court has stated that
"[W]hen a patent 'simply arranges old elements with each performing the same function it had been known to perform' and yields no more than one would expect from such an arrangement, the combination is obvious."
KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 , 417 , 127 S. Ct. 1727 , 167 L. Ed. 2d 705 (2007) (quoting Sakraida v. Ag Pro, Inc., 425 U.S. 273 , 282 , 96 S. Ct. 1532 , 47 L. Ed. 2d 784 (1976)).
Likewise, the Supreme Court has rejected rigid tests for obviousness and has emphasized that
[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.”
KSR Int'l v. Teleflex Inc., 550 U.S. 398, 415 (2007), at 416.
And has also emphasized that
“If a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability.”
KSR Int'l v. Teleflex Inc., 550 U.S. 398, 415 (2007), at 417.
Here, as explained by the rejection, the claimed invention is the combination of two prior art components, namely a known antiviral peptide taught by WO’103 and a known structure capable of being conjugated to antiviral peptides that would improve the potency of the antiviral peptide. Accordingly, no novel structures or unexpected results or properties have been identified on record, but instead, exactly as stated in the rejection of record, “each prior art element would merely performs its art-recognized function in combination as it does alone” (see rejection revised above; see also Rejection under 103 of record). In sum, arguments alleging a “universe of possibilities” appear to be conclusory arguments made in the absence of any supporting objective evidence, and are therefore not persuasive as explained above.
Allegations of unexpected results: It is the Examiner’s understanding that Applicant repeatedly alleges the existence of unexpected results commensurate in scope with the requirements of MPEP §716, §716.01, and §716.02, wherein such results are sufficient to rebut prima facie obviousness (see, e.g., Reply filed 5/12/2026 at 9-10 at bridging ¶, 10 at 1st full ¶). However, to establish such unexpected results, the allegations must be timely and supported by objective evidence commensurate in scope with the requirements of MPEP § 716 (see, e.g., 37 C.F.R. 1.132; see MPEP §§ 716.01, 716.01(a), 716.01(b), 716.01(c)); the evidence must establish that the expected results occur to an unexpected extent (see, e.g., MPEP § 716.02(a)(I)), on the basis of statistically and practically significant evidence (see, e.g., MPEP § 716.02(b)(I)), which is fully explained (see, e.g., MPEP § 716.02(b)(II)), commensurate in scope with the claimed invention (see, e.g., MPEP § 716.02(d)), and wherein a comparison of the claimed invention with the closest prior art of record is provided (see, e.g., MPEP § 716.02(e)). Furthermore, even if evidence satisfying MPEP §§ 716.02, 716.02(a), 716.02(b), 716.02(d), and 716.02(e) is set forth on record, such evidence may not be sufficient to rebut prima facie obviousness because the evidence of expected and unexpected results must be weighed (see, e.g., MPEP § 716.02(c)(I)) and the totality of the record considered (see, e.g., MPEP §§ 716.01(d), 716.02(f)), including teachings in the prior art and evidence of expected results which weigh in favor of a determination of obviousness (see, e.g., MPEP § 716.02(c)(II)). Here, the proffered evidence relied upon is Figure 8A, 12-14, 21G-I and J, and Figure 23; and paragraphs [0138] and [0150] (see, e.g., Reply filed 5/12/2026 at 9-10 at bridging ¶, 10 at 1st full ¶).
First, mere allegations that results are “surprising and unexpected” in the text of the Application, in the absence of objective supporting evidence commensurate in scope with the requirements of MPEP §§ 716, 716.01, and/or 716.02, are insufficient to satisfy the requirements of MPEP §§ 716, 716.01, and 716.02.
Second, allegations that the results were published in a scientific journal, in the absence of objective supporting evidence commensurate in scope with the requirements of MPEP §§ 716, 716.01, and/or 716.02, are insufficient to satisfy the requirements of MPEP §§ 716, 716.01, and 716.02. Standards for journal publications are not the same as standards for issuance of a patent.
Third, Figures 12-14, 21G-I and J, and Figure 23 do not clearly satisfy MPEP § 716.02(b) and MPEP § 716.02(e), because the proffered data does not provide a statistically or practically significant comparison of the claimed invention with the closest existing prior art of record, wherein such data and comparison is fully explained (see, e.g., MPEP § 716.02(b)(II)). Rather, the Figures either shown no statistical comparison, and/or fail to provide a comparison with the closest prior art of record but instead show a comparison with a “mock-treatment” (see, e.g., Spec. filed 4/13/2023 at ¶[0171], noting that “mock-treated” meant “vehicle, 2% DMSO in DI water”, rather than the closest existing prior art of record). Accordingly, such data fails to satisfy the requirements of MPEP §§ 716.02(b) and 716.02(e).
Fourth, regarding Figure 8A, this example is not properly explained as required (see, e.g., MPEP § 716.02(b)(II)), but is reasonably inferred to provide a comparison showing that the structure(s) of Pessi did, in fact, improve the antiviral potency of the known antiviral peptide of the primary reference (see, e.g., Spec. filed 4/13/2023 at ¶[0133]-¶[0134], Fig. 8A), and that the scope of the improvement observed was similar to the improvement predicted and expected in view of Pessi (see, e.g., Pessi at Fig. 2 on 4, Fig. 3 on 5, etc., showing improvement on a log scale; see also Pessi at 4 at col I to page 5 at bridging ¶, 5 at col II at 2nd to 3rd full paragraph, referring to 10-fold, and “150-fold and 6,000-fold” improvements). Accordingly, such data is not surprising or unexpected in view of Pessi, but instead the proffered data appears to merely confirm the exact expected and predicted result of Pessi, namely that such dimeric cholesterol tag would improve anti-viral potency of a known antiviral peptide by orders of magnitude. This is pertinent because per MPEP § 716.02(c)(II), states that “EXPECTED BENEFICIAL RESULTS ARE EVIDENCE OF OBVIOUSNESS”, rather than non-obviousness. Zero discussion or evidence explaining why the proffered data shows more than the expected and predicted results have been placed on record and clearly explained (see, e.g., MPEP § 716.02(b)(II), noting that Applicant has the burden to explain all proffered data in support of unexpected results).
Fifth, the pending claims are not commensurate in scope with the proffered data because the claims are not limited to the formulations and administration routes tested (compare proffered data with instant claims 64-69, noting that instant claims 65-69 are not limited to intranasal administration, but instead read upon all forms of administration, including topical, oral, ocular, subcutaneous, sublingual, etc., etc. Accordingly, the narrow scope of tested data is not commensurate in scope with the broad claim scope currently claimed, and therefore the proffered data does not reasonably appear to satisfy the requirements of MPEP § 716.02(d).
In sum, all arguments and proffered evidence in support of a determination of unexpected results has been fully considered, but not found persuasive as explained above. Accordingly, to date, zero evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record.
Accordingly, all applicable arguments raised by the Applicant have been fully considered but not found persuasive as explained above. Therefore, the claims remain rejected as set forth in the revised rejection above. All revisions were necessitated by Applicant amendments.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Figueira et al5 teaches and discloses and exemplifies a highly similar structures, namely HRC4, which comprises a structure of form
[(Viral peptide)-GSGSG-C-(MAL-PEG4-NH2]2-Chol]
(see, e.g., Figueira at Table 1 on 2). Accordingly, this structure is understood to be identical to the structure shown at instant Figure 11A except for the presence of a different HRC moiety (compare Figueira at 13 at §§ “peptide synthesis”, Table 1 on 2 showing HRC4 with instant Fig. 11A, showing both structures comprise two copies of a viral peptide, linked to a linker comprising GSGSGC to a maleimide derivative linked to PEG4, wherein both copies are conjugated to a single cholesterol moiety). This structure was disclosed as having antiviral applications, wherein the structure desirably utilized the viral peptide to inhibit viral infection at an entry stage, wherein such structures were suitable for intranasal administration, and were identified as desirably enhancing a viral peptides biodistribution and half-life, while increasing integration into a target cell membrane (see, e.g., Figueira at abs). The specific structure of HRC4 was reported as having the best in vitro efficacy profile (see, e.g., Figueira at Table 2 at 8), as crossing the human airway epithelium at the highest concentration (see, e.g., Figueira at Fig. 5 at 9), and that HRC4 could inhibit a viral infection in vivo (see, e.g., Figueira at 9 at 1st ¶, 10 at 1st full ¶, Fig. 7 on 10), wherein the general approach is reasonably inferred to be applicable to other viruses (see, e.g., Figueira at 12 at 1st full ¶, noting general statements that the disclosure “can be used to guide the design of effective antivirual fusion inhibitory peptides, in light of the coherent evidence here for the effects on peptide efficacy of specific lipid conjugation, dimerization, self-assembly properties, and membrane binding properties.
US2017/0216448A1 (Aug. 3, 2017; cited in previous action) teaches and discloses highly related dimeric structures (see, e.g., US’448 at Fig. 1D, reproduced in part below):
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Conclusion
No claims are allowed.
Applicant's amendment necessitated the new or revised 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RANDALL L BEANE whose telephone number is (571)270-3457. The examiner can normally be reached Mon.-Fri., 7 AM to 2 PM ET.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko G. Garyu can be reached at (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/RANDALL L BEANE/ Primary Examiner, Art Unit 1654
1 Pessi et al., A general strategy to endow natural fusion-protein-derived peptides with potent antiviral activity. PLoS One. 2012;7(5):e36833. doi: 10.1371/journal.pone.0036833. Epub 2012 May 16. PMID: 22666328; PMCID: PMC3353973; hereafter “Pessi”.
2 Pessi et al., A general strategy to endow natural fusion-protein-derived peptides with potent antiviral activity. PLoS One. 2012;7(5):e36833. doi: 10.1371/journal.pone.0036833. Epub 2012 May 16. PMID: 22666328; PMCID: PMC3353973; hereafter “Pessi”.
3 SEQ ID NO: 48 of WO’103 is DISGINASVVNIQKEIDRLNEVAKNLNESLIDLQEL.
4 WO’103 at claims 8 and 33 explicitly claim SEQ ID NO: 48 (e.g., HR-C4a), as one of only two enumerated compounds.
5 Figueira et al., In Vivo Efficacy of Measles Virus Fusion Protein-Derived Peptides Is Modulated by the Properties of Self-Assembly and Membrane Residence. J Virol. 2016 Dec 16;91(1):e01554-16. doi: 10.1128/JVI.01554-16. PMID: 27733647; PMCID: PMC5165226; hereafter “Figueira”; cited in previous action.
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