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 .
Priority
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in Australia on 1/19/2021. It is noted, however, that applicant has not filed a certified copy of the AU2021900114 application as required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) was submitted on 6/21/2024 before the mailing of a first office action. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.831(a) and 1.831(b). However, this application fails to comply with the requirements of 37 CFR 1.831-1.834. The examiner has noted that the sequences recited by claims 1 and 36 are not in the sequence listing. The sequence labeled “Formula I” in the specification at para. [0015] and the sequence at para. [0131] is also not in the sequence listing.
Applicant must provide:
• A replacement “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2., as well as
• A statement that identifies the location of all additions, deletions, or replacements of sequence information in the “Sequence Listing XML” as required by 1.835(b)(3);
• A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.835(b)(4);
• A statement that the “Sequence Listing XML” includes no new matter in accordance with 1.835(b)(5); and
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(b)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specific deficiency - Sequences appearing in the specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c).
The sequence labeled “Formula I” in the specification at para. [0015] and the sequence at para. [0131] require sequence identifiers. Peptide derivatives in Table 10, Table 11, and Table 12 also require sequence identifiers.
Claims 1 and 36 also recite peptide sequences that lack sequence identifiers.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specification
The disclosure is objected to because of the following informalities. The sequence labeled “Formula I” in the specification at para. [0015] and the sequence at para. [0131] require sequence identifiers. Peptide derivatives in Table 10, Table 11, and Table 12 also require sequence identifier. Appropriate correction is required.
The use of the term “Alexa Fluor”, which is a trade name or a mark used in commerce, has been noted in this application in para. [0058] and para. [0382]. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Status
Claims 1, 21, 23-25, 27, 31, 33-36, 56-58, 60, 61, 63, 64, 66, and 67, filed 7/19/2023, are pending. Claims 1, 21, 23-25, 27, 31, 33-36, 56-58, 60, 61, 63, 64, 66, and 67 are under examination.
Claim Objections
Claims 1, 21, 23-25, 27, 31, 33-36, 56-58, 60, 61, 63, 64, 66, and 67 are objected to because of the following informalities. Claims 1 and 36 recite peptide sequences that lack sequence identifiers. Claims 21, 23-25, 27, 31, 33, 34, 63, 64, 66, and 67 are dependent upon claim 1 and claims 56-58, 60, 61 are dependent upon claim 36 and therefore they are all objected to as well. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claims 1, 21, 23-25, 27, 31, 33-36, 56-58, 60, 61, 63, 64, 66, and 67 are 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.
Regarding claim 1, claim 1 recites the word “preferably”, which renders the claims indefinite for the following reasons:
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) is considered indefinite, since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(d). Note the explanation given by the Board of Patent Appeals and Interferences in Ex parte Wu, 10 USPQ2d 2031, 2033 (Bd. Pat. App. & Inter. 1989), as to where broad language is followed by "preferable" and then narrow language. The Board stated that this can render a claim indefinite by raising a question or doubt as to whether the feature introduced by such language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Note also, for example, the decisions of Ex parte Steigewald, 131 USPQ 74 (Bd. App. 1961); Ex parte Hall, 83 USPQ 38 (Bd. App. 1948); and Ex parte Hasche, 86 USPQ 481 (Bd. App. 1949). In the present instance, claim recites the broad recitation, and the claim also recites the narrower statement of the range/limitation.
Regarding claim 21, this claim also recites “preferably” and therefore is rejected for the same reasons as described above.
Regarding claim 25, the phrase "for example" renders the claim indefinite because it is unclear whether the limitation following the phrase is part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 31, the phrase "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 36, this claim also recites “preferably” and therefore is rejected for the same reasons as described above.
Regarding claim 58, the phrase "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 61, the phrase "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 67, the phrase "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claims 21, 23, 24, 25, 27, 31, 33, 34, 35, 63, 64, 65, 66, and 67, these claims all depend from claim 1 and fail to resolve the indefiniteness described above. Consequently, these claims are also rejected.
Regarding claims 56, 57, 58, 60, and 61, these claims all depend from claim 36 and fail to resolve the indefiniteness described above. Consequently, these claims are also rejected.
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 63, 64, 66, and 67 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for prophylactic treatment of or decreasing likelihood of developing cancer in a subject, wherein the cancer comprises at least one PD-L1 overexpressing cell, does not reasonably provide enablement for eliminating cancer altogether wherein the cancer comprises at least one PD-L1 overexpressing cell. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is "reasonable" or is "undue." Consistent with Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the Wands factors continue to provide a framework for assessing enablement in a utility application or patent, regardless of technology area. Guidelines for Assessing Enablement in Utility Applications and Patents in View of the Supreme Court Decision in Amgen Inc. et al. v. Sanofi et al., 89 FR 1563 (January 10, 2024). These factors include, but are not limited to:
(A) The breadth of the claims;
The breadth of the claims center around how many cancers are involved with PD-L1 overexpression. As described below, this is a large number of cancers.
(B) The nature of the invention;
The invention is a method of treating or preventing cancer in a subject, wherein the cancer comprises at least one PD-L1 overexpressing cell, comprising administering to the subject a PD-L1 bicyclic peptide mimetic.
(C) The state of the prior art;
Cha et al. (Cha, et al. Molecular cell 76.3: 359-370 (2019)) discloses that many types of cancer are associated with PD-1 and the ligand PD-L1: “ (Cha et al., page 359, col. 1, para. 2): “In many human cancers, including renal cell carcinoma (RCC), breast cancer, colorectal cancer, gastric cancer, non-small cell lung cancer (NSCLC), papillary thyroid cancer, and testicular cancer (Thompson et al., 2004), high PD-L1 expression is detected and associated with poor prognosis (Ohaegbulam et al., 2015). Indeed, the binding between PD-L1 on cancer cells with PD-1 on tumor-infiltrating T cells (TILs) activates Src homology region 2 domain-containing phosphatases (SPH2s), leading to suppression of the T cell receptor (TCR) pathway and inhibition of T cell activity. Moreover, interruption of immune surveillance promotes cancer cell survival by exploiting PD-L1/PD-1 signaling (Schildberg et al., 2016).”
However, Tsanev (Tsanev, R. J. BUON 10: 309-318 (2005)) discloses that cancer cells may possess many different survival strategies including: 1) Reactivation of Telomerase, 2) Suppression of Apoptosis, 3) Elimination of Effector Cells, 4) Shedding of Soluble Receptors, 5) Neutralization of Tumor Suppressor Genes, 6) Development of a Detoxicating Efflux Pump, 7) Neoangiogenesis, 8) Overcoming and Utilizing Hypoxia, 9) Other Rescue Mutations, and 10) Access-Restriction Factors. (Tsanev, pages 313-315).
(D) The level of one of ordinary skill;
A person of ordinary skill in the art in the field of fusion proteins is usually at least a Master’s level education.
(E) The level of predictability in the art;
Protein-protein interactions that govern the interactions between PD-1 and PD-L1 and the other molecules in the oncogenic pathways are unpredictable in general. Regarding proteins, a single point mutation can change the biophysical properties of a protein: “In summary, we have shown that the structural changes in the fibrillar state of the Aβ42 peptide that are observed to occur upon introduction of single point mutations can be accompanied by changes in the dominance of the microscopic processes by which these aggregates are themselves formed.” (Bolognesi et al. ACS Chem Bio 9:2 (2013) page 381 col. 2 para. 3) and “In summary, while ovispirin-1 and novispirin G-10 both had solution structures that were helical and amphipathic in the presence of TFE, a relatively simple change in their primary structure (a single glycine–isoleucine exchange) had profound effects on their respective toxicities for human erythrocytes and epithelial cells.” (Sawai et al. Protein Eng. 15:3 (2002) page 232 col. 1 para. 3).
Furthermore, many substitutions result in non-functional aggregates. Wang (Wang, et al. MAbs. Vol. 1. No. 3. Taylor & Francis, (2009)) discloses a variety of aggregation prone motifs that occur in commercial antibodies (Wang, page 262, Table 2).
(F) The amount of direction provided by the inventor and the existence of working examples and the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Applicants show definitive examples of the ability of the disclosed peptides to modulate the translocation of PD-L1 and thereby influence cancer cells utilizing this pathway. However, the ability to modulate other known cancer survival strategies is not shown.
Regarding claim 63, claims 63 recites: “A method of treating or preventing cancer in a subject, wherein the cancer comprises at least one PD-L1 overexpressing cell, comprising administering to the subject a PD-L1 bicyclic peptide mimetic of claim 1.”
Furthermore, the specification at para. [0120] recites: “As used herein, the terms "prevent", "prevented" or "preventing", refer to a prophylactic treatment which increases the resistance of a subject to developing the disease or condition or, in other words, decreases the likelihood that the subject will develop the disease or condition as well as a treatment after the disease or condition has begun in order to reduce or eliminate it altogether or prevent it from becoming worse. These terms also include within their scope preventing the disease or condition from occurring in a subject which may be predisposed to the disease or condition but has not yet been diagnosed as having it.” (Emphasis added).
The data provided enables a scope including prophylactic increasing of resistance or reduction of likelihood of developed of claimed diseases. However, due to the wide breadth of cancers in which PD-L1 is involved and the wide breadth of cancer defense systems, the provided data does not support elimination of any cancer for which PD-L1 is overexpressed in at least one cell. Consequently, the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with claim 63 and claim 63 is rejected.
Regarding claim 64, claim 63 is rejected as described above. Claim 64 recites the broad categories of “ cancer cell” and “cancer stem cell”. For the reasons described above, the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with claim 64 and claim 64 is rejected.
Regarding claim 66, claim 63 is rejected as described above. Claim 66 recites the case where the cancer is selected from breast, prostate, lung, bladder, pancreatic, colon, liver, or brain cancer, or melanoma, or retinoblastoma. These are very broad categories, and while all have PD-L1 involvement, they also include cancer types with multiple defense mechanisms. For the reasons described above, the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with claim 66 and claim 66 is rejected.
Regarding claims 67, claim 63 is rejected as described above. Claim 67 further recites the case wherein further comprising administering at least one further cancer therapies (e.g., a chemotherapeutic agent). Broad categories of cancers are still claimed. For the reasons described above, the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with claim 67 and claim 67 is rejected.
Closest Prior Art
Ogawa et al. US20180113131A1, published 4/26/2018, discloses SEQ ID NO: 4:
LVILGAILLCLGVALTFIFRLRKGRMMDVKKCGIQDTNSKKQSAETGFHCVSQDGLNLLT
S
The following section of SEQ ID NO: 4: LTFIFRLRKGRMMDVKK partially matches the general formula in the case where
X1 is absent
X2 is threonine
X3 is phenylalanine
X4 is arginine
X5 is arginine
X6 is methionine
X7 is methionine
X8 is aspartic acid
X9 is lysine
X10 is lysine.
C1 and C2 are absent in SEQ ID NO: 4, which is the point of novelty.
SEQ ID NO: 4 is aligned against Applicant SEQ ID NO: 1 below for further comparison:
LENGTH: 50
TYPE: PRT
ORGANISM: Homo sapiens
Query Match 55.2%; Score 64; Length 50;
Best Local Similarity 89.5%;
Matches 17; Conservative 0; Mismatches 0; Indels 2; Gaps 2;
Qy 3 LTFIFCRLRKGRCMMDVKK 21
||||| |||||| ||||||
Db 15 LTFIF-RLRKGR-MMDVKK 31
This peptide, however, lacks the critical cysteine residues and furthermore, is not a bicyclic peptide. The prior art does not teach or suggest the insertions at these positions to result in Applicant Formula X1C1LX2X3IFC2X4LRKGX5C3X6X7X8X9KX10 or Applicant SEQ ID NO: 1.
Conclusion
No claim is allowed.
Claims 1, 21, 23-25, 27, 31, 33-36, 56-58, 60, 61, 63, 64, 66, and 67 are objected to.
Claims 1, 21, 23-25, 27, 31, 33-36, 56-58, 60, 61, 63, 64, 66, and 67 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to David Paul Bowles whose telephone number is (571)272-0919. The examiner can normally be reached Monday-Friday 8:30-5:00.
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 Garyu can be reached on (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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/DAVID PAUL BOWLES/ Examiner, Art Unit 1654
/LIANKO G GARYU/ Supervisory Patent Examiner, Art Unit 1654