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 57-76 are pending and 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 57-76 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 6/06/2024 (11 pages) and 6/06/2024 (8 pages) are each acknowledged and presently considered.
Applicant should note that one or more documents disclosed on the IDS form submitted on 6/06/2024 (11 pages) and 6/06/2024 (8 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).
Claim 57 is representative of the pending claim scope. Applicable claim interpretations are set forth below.
“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).
Claim 61 attempts to incorporate one or more Figures by reference (e.g., claim 61 refers to Figure 11A), which is improper per MPEP § 2173.05(s). MPEP § 2173.05(s) states that
[w]here possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.
Here, if Applicant meant to incorporate the Figure by reference, the incorporation is improper because no necessity has been asserted or established. Furthermore, simply reciting sequence identifiers is common in the art, and circa 2025 simply cutting and pasting a figure into a claim set is routine using modern software. Accordingly, the present record does not evidence or suggest the existence of any “exceptional circumstances where there is no practical way to define the invention”. This issue has necessitated rejections and objections as set forth below. For purposes of applying prior art under 35 USC 102 and 103, the reference to Figure 11A is understood to be a compound of form
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Wherein the wavy line represents a bond between a cysteine and a Maleimide derivative.
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).
Claim 62 recites “means for linking the two peptides to the cholesterol tag”. The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked. As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function. Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function. Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
Additional claim interpretations are set forth below.
Specification and Drawings
Sequence Listing: The instant disclosure is objected to for not complying with 37 C.F.R. 1.821 as detailed in MPEP §§ 2421–2424. Specifically, the instant application does not comply with 37 C.F.R. 1.821(b)-(e). The instant disclosure contains references or disclosures of amino acid sequences that should be accompanied by a sequence listing and identified using "SEQ ID NOs” as prescribed (see, MPEP §§ 2421–2424). Specifically, the instant application discloses sequences at ¶¶[0006]-[0007], [0009], [0012]-[0015], [0020], [0040]-[0041], [0046], [0065]-[0066], [0071], [0089]-[0090], [0092], [0095]-[0098], [0103], [0159], Fig. 5, Fig. 6B, 11A-C, that must be accompanied by a SEQ ID NO.
Appropriate correction is required.
Drawings
The drawings are objected to under 37 CFR 1.83(a) because they fail to show colors as described in the specification (see, e.g., Spec. filed 04/13/2023 at ¶[0064] and Fig. 4 referring to “red” and “blue”; ¶[0073] and Fig. 13 referring to “red” and “blue”; ¶[0076] and Fig. 16 referring to “red” and “green”; ¶[0077] and Fig. 17 referring to “orange” and “purple”; ¶[0078] and Fig. 18 referring to “orange” and “purple”; ¶[0079] and Fig. 19 referring to “red”, “blue”, and “green”; ¶[0081] and Fig. 21 referring to “red” and “green”; ¶[0082] and Fig. 22 referring to “red” and “blue”; ¶[0083] and Fig. 23 referring to “red” and “green”; ¶[0084] and Fig. 24 referring to “red” and “green”; ¶[0085] and Fig. 25 referring to “red” and “green”). Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Claim Objections
Claim 61 is objected as follows: Claim 61 attempts to incorporate one or more Figures by reference (e.g., claim 61 refers to Figure 11A), which is improper per MPEP § 2173.05(s). MPEP § 2173.05(s) states that
[w]here possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.
Here, if Applicant meant to incorporate the Figure by reference, the incorporation is improper because no necessity has been asserted or established. Furthermore, simply reciting sequence identifiers is common in the art, and circa 2025 simply cutting and pasting a figure into a claim set is routine using modern software. Accordingly, the present record does not evidence or suggest the existence of any “exceptional circumstances where there is no practical way to define the invention”, and therefore the attempt to incorporate Figure 11A is improper.
Claim Rejections
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 61 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 61 recites the limitation "FIG. 11A" at line 2. There is insufficient antecedent basis for this limitation in the claim. If this is an attempt to incorporate by reference the structure shown at instant Figure 11A, this is improper (see claim objection, above). Even assuming arguendo that the structure of Figure 11A was imported to claim 61, the claim scope would remain rejected because the wavy line is undefined in the image. Accordingly, claim 61 is rejected as indefinite. For purposes of applying prior art under 35 USC 102 and 103, the reference to Figure 11A is understood to be a compound of form
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Wherein the wavy line represents a bond between a cysteine and a Maleimide derivative. This rejection could be overcome by amending claim 61 to explicitly recite the desired structure.
Claim 62 recites “means for linking the two peptides to the cholesterol tag”, which invokes 35 USC 112(f), and is therefore interpreted to “cover the corresponding structure, material, or acts described in the specification and equivalents thereof" (see, e.g., MPEP §§ 2173.01(II), 2173.05). However, per § 2181(II),
35 U.S.C. 112(f) states that a claim limitation expressed in means- (or step-) plus-function language "shall be construed to cover the corresponding structure…described in the specification and equivalents thereof." "If one employs means plus function language in a claim, one must set forth in the specification an adequate disclosure showing what is meant by that language. If an applicant fails to set forth an adequate disclosure, the applicant has in effect failed to particularly point out and distinctly claim the invention as required by the 35 U.S.C. 112(b) [or the second paragraph of pre-AIA section 112 ]." In re Donaldson Co., 16 F.3d 1189, 1195, 29 USPQ2d 1845, 1850 (Fed. Cir. 1994) (en banc).
Furthermore, per MPEP § 2181(II)(A) and (C) explain that a claim that properly invokes 35 USC 112(f) may be indefinite if the language does not correspond to a description, wherein “The structure disclosed in the written description of the specification is the corresponding structure only if the written description of the specification or the prosecution history clearly links or associates that structure to the function recited in a means- (or step-) plus-function claim limitation” (see, e.g., MPEP § 2181(II)(C)). Per MPEP § 2181(III)(2)-(3), a rejection under 35 USC 112(b) is appropriate
(2) when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph is invoked and there is no disclosure or there is insufficient disclosure of structure, material, or acts for performing the claimed function; and/or
(3) when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph is invoked and the supporting disclosure fails to clearly link or associate the disclosed structure, material, or acts to the claimed function.
Following the analysis provided at MPEP § 2181(III) and MPEP § 2173.05(g), Examiner notes that the originally filed disclosure lacks a clear and sufficient disclosure of structures, material or acts for performing the claimed function that clearly link or associate the disclosed structure, material or acts to the claimed function; furthermore, in the absence of clear guidance, an artisan would not reasonably be aware of what structures were “equivalents thereof”. Although the specification identifies PEG linkers, the specification does not provide guidance regarding what the inventor deems “equivalents” of PEG for purposes of interpreting “means for linking the two peptides to the cholesterol tag”. Accordingly, it is unclear if XTEN sequences, viral particles, quantum dots, etc. are encompassed as “equivalents” within the claim scope, or if the language is more narrowly limited to PEG repeats (e.g., PEG1-50). Because it is unclear what structures are included or excluded by such language, an artisan would not know how to avoid infringement under 35 USC §112(b) (see also MPEP §§ 2173, 2173.05(g)); therefore, the claim is indefinite. For purposes of applying prior art under 35 USC 102 and 103, the language is understood in view of Figure 11 and ¶¶[0010], [0016], [0122], to read upon at least PEG1-24.
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 57-76 are rejected under 35 U.S.C. 103 as being unpatentable over WO2005/077103 in view of Pessi et al.1.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding rejection(s) and also in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. Instant claims 57, 59, 62, 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] and similar structures. Additional claim interpretations are set forth below.
Regarding instant claims 57-76, 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: 482, claims 1, 5, 8, 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 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, 59, 62, 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 the 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 instant claim 61 and the compound shown at 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 claims 58, 60, 61, 63, and instant SEQ ID NO: 5, 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. However, as noted in the exemplified embodiment of Pessi, the linker of GSGSGC 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, it would necessarily yield SEQ ID NO: 5. 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 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 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 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 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.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Figueira et al3 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) teaches and discloses highly related dimeric structures (see, e.g., US’448 at Fig. 1D, reproduced in part below):
PNG
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155
718
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Conclusion
No claims are allowed.
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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 SEQ ID NO: 48 of WO’103 is DISGINASVVNIQKEIDRLNEVAKNLNESLIDLQEL.
3 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”.