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 without traverse of Group I, claims 1, 3-6 and 14 in the reply filed on 3/2/26 is acknowledged.
Claims 7-11, 15, 17, 20, 22 and 23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 3/2/26.
Applicant’s election without traverse of the fusion peptide of SEQ ID NO:3 as the elected species in the reply filed on 3/2/26 is acknowledged.
Claim Status
Claims 1, 3-11, 14, 15, 17, 20, 22, 23 are pending.
Claims 2, 12, 13, 16, 18, 19, 21 are cancelled.
Claims 7-11, 15, 17, 20, 22 and 23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 3/2/26.
Claims 1, 3-6 and 14 are pending and under examination.
Claims 1, 3, 5, 6 and 14 are rejected.
Claim 4 is objected to.
Priority
The instant application, filed 04/20/2023 is a National Stage entry of PCT/AU2021/050770 , International Filing Date: 07/16/2021
claims foreign priority to 2020902478, filed 07/17/2020.
Information Disclosure Statement
The Examiner has considered the reference(s) provided in the 4/20/23 Information Disclosure Statement, and provides a signed and dated copy of such herewith.
Claim Interpretation
The claim limitations are given their broadest reasonable interpretation (BRI) consistent with the specification, MPEP 2111, and under the BRI, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification, MPEP 2111.01.
Claim 14 includes the limitation “instructions as to how to use the fusion peptide.” The specification does not specify in what form(s) is/are the instructions. Based on the ordinary and customary meaning of instructions that would be provided in a kit with a therapeutic or diagnostic agent such as the instantly claimed fusion peptide, the claim 14 instructions are interpreted as written instructions.
Further regarding claim 14, consistent with MPEP 2111.02 II, which states in part, “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction,” claim 14’s preamble intended use “for treating cancer in a subject” preamble is not considered a limitation and is of no significance to claim construction.
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 1, 3, 5, 6 and 14 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 encompasses variants of SEQ ID NO:1 in its fusion peptide, claim 3 encompasses variants of SEQ ID NO:2 in its RGD-motif containing peptide, and claim 5 encompasses variants of SEQ ID NO:3.
Paragraph 65 of the specification states the following:
[0065] A “variant” of a polypeptide (e.g. melittin fusion peptide) comprises an amino acid sequence wherein one or more amino acid residues are inserted into, deleted from and/or substituted into the amino acid sequence relative to another polypeptide sequence, but which retains the biological activity of the original polypeptide sequence by reference to assays known in the art. Variants include fusion proteins. A “variant” of a melittin fusion peptide comprises an amino acid sequence wherein one or more amino acid residues are inserted into, deleted from and/or substituted into the amino acid sequence relative to the melittin fusion peptide, which retains melittin fusion peptide like biological activity, which can be measured by assays known in the art, such as cell viability assays.
The claimed subject matter is not supported by an adequate written description. There are insufficient guidance, structure/function relationships such as correlations between a particular structure and a function, and/or other relevant disclosure, nor examples that are representative of the diversity of the genera encompassed by the variants in claims 1, 3 and 5.
The skilled artisan cannot envision the detailed chemical structure alternatives (i.e., amino acid sequences) of the encompassed peptides which have the respective required activity/function without further testing, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of identification. Adequate written description requires more than a mere statement that it is part of the invention. The compound itself is required; in this case at least a sufficient number of species that are representative of the diversity of each respective genus, and/or a disclosure of what is critical as far as sequence(s) and what does not work to achieve a particular claimed activity/function. Here, given the breadth of possible modifications per “variant” – which nonetheless requires that any such variant retains the biological activity of the original polypeptide sequence, the skilled artisan is left to determine what range of variations can still provide some level of relevant biological activity. This is leaving completion of the invention to someone else. See also Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016 (Fed. Cir. 1991). One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483 (BPAI 1993). 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, the full breadth of the claims does not meet the written description provision of 35 U.S.C. §112, first paragraph. Applicants are reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. § 112 is severable from its enablement provision (see page 1115).
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
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.
Claim(s) 1, 3, 5 and 14 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Zhu et al., Protein Expression and Purification, Volume 76, Issue 2, April 2011, Pages 184-189 (Zhu), as evidenced by GenBank Accession Number HQ436980, dated 7/25/16, 1 page.
Claim 1 is directed to a fusion peptide comprising (1) SEQ ID NO: 1, or a variant thereof, and (2) an RGD-motif containing peptide, wherein the fusion peptide binds to the integrins αvß6 and αvß3.
Zhu teaches constructing a fusion gene the first segment of which “encodes 73 amino acids of snake disintegrin, following it is the linker peptide. The final segment of the fusion gene encodes the melittin. The complete sequence of the construct has been deposited in GenBank, the accession number is HQ436980,” page 186.
Zhu also teaches, “The Disintegrin-Conj-Mel protein contained a disintegrin of Gloydius ussuriensis with an Arg-Gly-Asp (RGD) motif. The RGD motif can bind to integrin αvβ3 expressed on the surface of tumor cells and so selectively concentrate the targeted toxin on tumor cells surfaces. The cytotoxic agent melittin can induce membrane disruption leading cell to death. Between the targeting domain and the cytotoxic agent, we inserted a peptide linker composed of a flexible chain to providing flexibility and an uPA cleavable site. Disintegrin-Conj-Mel offers an attractive alternative approach to kill tumor cell on the surface instead of the way that most of the targeted drugs have to be internalized. The Disintegrin-Conj-Mel was expressed with high bioactivity using the eukaryotic expression system of Pichia pastoris. The ability to produce relatively large quantities of this fusion protein will facilitate future studies to further improve this targeting technique for anti-cancer treatments,” page 185.
As evidenced by GenBank Accession Number HQ436980, the fusion peptide encoded by Zhu’s fusion gene is:
EAGEECDCDSPANPCCDAATCKLRPGAQCAEGLCCEQCRFMKEGTVCRIARGDDMDDYCNGISAGCPRNPFHASGGGGSGGGGSGGGGSRVGIGAVLKVLTTGLPALISWIKRKRQQ, in which the RGD is underlined and the portion that corresponds exactly to instant SEQ ID NO:1 is shown in bold.
From the above the fusion protein binds to integrin αvβ3, but it is not stated nor shown that this Zhu fusion protein also binds to integrin αvβ6 as required by claim 1.
The Zhu reference discloses all the limitations of a claim except binding to integrin αvβ6, and the examiner cannot determine whether or not the Zhu reference, particularly the above fusion peptide, inherently possesses binding to integrin αvβ6, which anticipate or render obvious the claimed invention but at least based on Zhu and the evidentiary reference the examiner has basis for shifting the burden of proof to applicant, as in In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980). See MPEP §§ 2112 - 2112.02.
Based on the above, Zhu as evidenced by GenBank Accession Number HQ436980 anticipates claim 1, and also claims 3 and 5 based on the above fusion peptide encompassed by a variant of SEQ ID NO:2 as to claim 3 and a variant of SEQ ID NO:3 as to claim 5.
Because the claim 14 instructions are interpreted as written instructions, and the examiner has determined based on the paucity of additional information about the content of the instructions that the instructions are not functionally or structurally related to the associated physical substrate – the fusion peptide of claim 1, these instructions are owed no patentable weight, and claim 14 is rejected as anticipated on the same basis as claim 1.
In the alternative, claims 1, 3-5 and 14 would have been obvious. The technical reasoning to support obviousness is that RGD comprising peptides have been and are known to be promiscuous as to binding to multiple integrins1, and may bind a number of related integrins albeit at differing strengths of binding as that may be measured in the art. There is no required minimum binding required to meet the “binds” functional limitation of claim 1, and any de minimis binding would meet the limitation to bind to integrin αvβ6.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Zhu et al., Protein Expression and Purification, Volume 76, Issue 2, April 2011, Pages 184-189 (Zhu), as evidenced by GenBank Accession Number HQ436980, dated 7/25/16, 1 page, as applied to claim 1 above, and further in view of Sun et al., Toxins 2015, 7, 423-438 (Sun).
The rejection of claim 1 is set forth above.
Claim 6 is directed to “A pharmaceutical composition comprising the fusion peptide of claim 1.
Zhu does not explicitly recite its fusion peptide in a pharmaceutical composition form.
The level of ordinary skill in the art is high.
Sun further evaluates the “DLM” conjugate made per the Zhu reference, see page 425, first two paragraphs and note that the reference numbered 39 is the Zhu reference.
Sun, page 434, teaches, “FITC (fluorescein isothiocyanate), native disintegrin and DLM were dissolved in buffer (7.56 g NaHCO3, 1.06 g Na2CO3, and 7.36 g NaCl, in 1 L water), respectively (20 mg native disintegrin or DLM at 2 mL, 7.8 mg FITC at 3 mL).” The Sun fusion peptide identified as DLM when dissolved in this buffer is a pharmaceutical composition.
Therefore claim 6 would have been obvious and is rejected under this section.
Allowable Subject Matter
Claim 4 objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form.
Art Made of Record
Ludwig et al., Cancers 2021, 13, 1711, 55 pages, published 4/4/21 so not prior art, provides a review of RGD-binding integrins.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH FISCHER whose telephone number is (571)270-7925, and whose direct facsimile number is (571)270-8925. The examiner can normally be reached on Monday to Friday, 9:00 AM to 5:00 PM, however noting that the examiner will not normally be working on Monday/Tuesday and on Wednesday-Friday on alternating weeks, but will promptly answer messages upon his return to work.
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/JOSEPH FISCHER/Primary Examiner, Art Unit 1658
1 While not stating that what applicant states in para 89 of the specification is an admission, this nonetheless appears to support what was known in the art, namely that “eight integrin dimers, i.e., avß1, avß3, avß5, avß6, avß8, a5ß1, a8ß1, and allbß3, recognize the tripeptide RGD-motif within extracellular matrix proteins.”