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 .
DETAILED ACTION
Response to Election/Restriction filed on January 5, 2026 is acknowledged. Claims 2, 17 were canceled and claims 1, 3-16, 18-33 are pending.
Election/Restrictions
Applicant elected with traverse Group II (claims 18-30, 33) drawn to a composition and with traverse SEQ ID NO:26 in the response filed January 5, 2026.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP 818.03(a)).
The restriction is deemed proper and is made FINAL in this office action. Claims 1, 3-16 and 31-32 are withdrawn from consideration as being drawn to a non-elected invention/species. Claims 18-30 and 33 are examined on the merits of this office action.
Sequence Compliance
This application fails to comply with the requirements of 37 C.F.R 1.821-1.825 for the reasons set forth on the attached Notice to Comply With Requirements For Patent Applications Containing Nucleotide Sequence And/or Amino Acid Sequence Disclosures. Applicant must comply with the requirements of the sequence rules (37 CFR 1.821-1.825) before the application can be examined under 35 U.S.C 131 and 132. Each sequence disclosed must appear separately in the “Sequence Listing.” Each sequence set forth in the “Sequence Listing” must be assigned a separate sequence identifier. Applicant failed to include sequence identifiers in either Figures 1, 10 or in the description of Figures 1, 10.
Drawings
The drawings are objected to because according to 37 CFR 1.821(b) the sequence information so conveyed must still be included in a "Sequence Listing” and the sequence identifier (“SEQ ID NO:X”) must be used, either in the drawing or in the “Brief Description” of the Drawings. Figures 1, 10 comprises sequences without sequence identifiers. There are no sequence identifiers listed in Figures 1, 10 or the description of Figures 1 and 10. 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.
Specification Objection
The specification is objected to for containing referring to sequences without also identifying them by the sequence identifier assigned to them in the sequence listing as required by 37 CFR 1.821(d). The specification discloses peptide sequences, and these are missing their respective sequence identifiers. For example, the sequence found on pages 4, 17-18, 20-22, 24-25 and 28-29, disclose peptide sequences, but these are missing their sequence identifiers. The examiner would like to bring the applicant’s attention to the following excerpt from MPEP §2422.03:
37 CFR 1.821(d) requires the use of the assigned sequence identifier in all instances where the description or claims of a patent application discuss sequences regardless of whether a given sequence is also embedded in the text of the description or claims of an application. This requirement is also intended to permit references, in both the description and claims, to sequences set forth in the "Sequence Listing" by the use of assigned sequence identifiers without repeating the sequence in the text of the description or claims. Sequence identifiers can also be used to discuss and/or claim parts or fragments of a properly presented sequence. For example, language such as "residues 14 to 243 of SEQ ID NO:23" is permissible and the fragment need not be separately presented in the "Sequence Listing." Where a sequence is embedded in the text of an application, it must be presented in a manner that complies with the requirements of the sequence rules.
The proper way to reference a peptide sequence is for example, GLLXLLELLLXAAG (SEQ ID NO: 39 ) (see 37 CFR 1.821(d)). This error should be corrected throughout the Applicant’s specification.
Claim Rejections - 35 USC § 112, First Paragraph
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 28-30 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), paragraph, because the specification, while being enabling for treatment of specific cancer types with peptides of instant claim 18 (breast cancer cells, cervical cancer cells and bone cancer cells) does not reasonably provide enablement for treatment or prevention against any cancer type. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims. The treatment of cancer generally cannot possibly be considered enabled for the many reasons stated below.
To comply with the enablement requirements of 35 U.S.C. §112, first paragraph, a specification must adequately teach how to make and how to use a claimed invention throughout its scope, without undue experimentation. Plant Genetic Systems N.V. v. DeKalb Genetics Corp., 315 F.3d 1335, 1339, 65 USPQ2d 1452, 1455 (Fed. Cir. 2003). There are a variety of factors which may be considered in determining whether a disclosure would require undue experimentation. These factors include: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
The Nature of the Invention/ The breadth of claims
Claim 28 claims “A kit for treating or preventing cancer comprising a pharmaceutically acceptable composition comprising the peptide of claim 18 and one or more pharmaceutically acceptable excipients.” Claim 29 claims wherein the cancer is breast cancer (which encompasses treatment and prevention of breast cancer) and claim 30 claims a chemotherapeutic agent. The claims encompass treating/preventing any cancer type.
The breadth of the claims exacerbates the complex nature of the subject matter to which the present claim is directed. The claims are extremely broad due to the vast number of possible cancers and tumor types encompassed by the claims and given the claim encompasses treatment and prevention. Furthermore, there are numerous subspecies within the species of cancers. For example, cancer is not a single disease, or cluster of closely related disorders.
There are hundreds of cancers, which have in common only some loss of controlled cell growth. Cancers are highly heterogeneous at both the molecular and clinical level, something seen especially in, for example, the cancers of the breast, brain and salivary glands. They can occur in pretty much every part of the body. There is not a known one compound that can treat all cancer types given the variability (causes and mechanisms of pathogenesis) in cancer types (See Mechanisms of Carcinogenesis, 2010, International Agency for Research on Cancer, Section 3, page 190, column 1, and first paragraph).
State of the Prior Art
While the state of the art is relatively high with regard to treatment of specific cancer types, the state of the art with regard to using peptides to treat/prevent cancers/tumors broadly or lacking. There is no one treatment (or peptide) in the prior art or in the Applicant’s specification that will have anticancer activity against any cancer type or prevent any cancer type.
A review of the relevant art yielded a diverse array of treatment options for those suffering from various forms of cancer. Traditional therapies include chemotherapy, radiotherapy and surgery.
Regarding antimicrobial peptides (peptides found in instant claim 1), the art is lacking. However, Schweizer discusses cationic amphiphilic peptides with cancer selectivity toxicity. Schweizer teaches “During the last two decades cationic amphiphilic peptides and peptide sequences (CAPs) with cancer-selective toxicity have appeared. Based on their spectrum of anticancer activity CAPs can be divided into two major classes. The first class includes peptides that are highly potent against both bacteria and cancer cells, but not against mammalian cells. The second class includes peptides that are toxic to bacteria, and both mammalian cancer and non-cancer cells. Most antimicrobial and anticancer CAPs share a common membranolytic mode of action that results either in the selective disruption of the cancer cell membrane or permeation and swelling of mitochondria. The electrostatic attraction between the negatively charged membrane components of bacterial and cancer cells and CAPs is believed to play a crucial role in the disruption of bacterial and cancer cell membranes. This mode of action appears to bypass established resistance mechanisms. However, it is currently unclear as to why some CAPs kill cancer cells when others do not. In addition, non-membranolytic mode of actions of CAPs is increasingly recognized to contribute significantly to the anticancer activity of certain CAPs. The development of CAP-based chemotherapeutics is complicated due to the traditionally poor pharmacokinetic properties and high manufacturing costs of peptides and the low intrinsic selectivity for cancer cells. Peptidomimetic approaches combined with novel selective delivery devices show promise in overcoming some of these obstacles” (See abstract). Schweizer teaches that the “CAP cecropin which displays anticancer activity against ovarian, carcinoma, breast carcinoma and leukemia cells”. However, Schweizer does not disclose use of a peptide of the instant claim or any one amphiphilic antimicrobial peptide for using against cancer inhibition broadly.
Though Applicants have the peptides have anti-breast cancer/cervical cancer/bone cancer activity in vitro, this is not sufficient for enablement for being used treat or prevent any cancer type given the vast number of cancer cell types, various mechanism of pathogenesis of each cancer cell type, the varying methods of treatment and the unpredictability of treating cancer broadly.
Furthermore, prior art regarding treatment/prevention of cancer broadly with a single compound is non-existent.
The Predictability in the art
Cancer therapy is highly unpredictable. The specification itself shows variable selectivity across cell lines, differences between 2D and 3D cultures, differential toxicity across normal vs. cancer cells.
Thus, one cannot reasonably extrapolate to all cancers or to prevention..
The Relative Skill of Those in the Art
A skilled artisan in oncology drug development would require pharmacokinetics, toxicology, maximum tolerated dose, in vivo efficacy, tumor penetration etc… none of which are provided.
Amount of Guidance/The Presence or Absence of Working Examples
The specification provides in vitro toxicity assays (MTT); mammosphere assays, liposome leakage assays, MD simulations. However, the specification does not provide an in vivo tumor models, any animal data, and dosage guidance, formulation guidance and any prevention data. There is no guidance on how to treat human patients. Working examples are limited to in vitro cytotoxicity against specific cell lines (breast cancer, bone cancer and cervical cancer); liposome and mechanistic assays. There are no working examples of treating or preventing cancer in a subject.
The quantity of experimentation needed
Given the fact that, historically, the development of new cancers drugs has been difficult and time consuming, and especially in view of the factors stated above, the quantity of experimentation needed is expected to be great.
MPEP 2164.01(a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here.
Because the specification does not enable the full scope of treating or preventing cancer across all cancer types and subjects without undue experimentation, claims 28-30 are rejected under 35 U.S.C. 112(a) for lack of enablement.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 24 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 24 claims “the peptide of claim 18, wherein the peptide sequence consists of the motif GLLxLLxLLLxAAG (SEQ ID NO:38)”. However, claim 18 claims “A peptide having a sequence comprising the motif GLLxLLELLLxAAG (SEQ ID NO:39)…”. Claim 18 requires that a glutamic acid be at position 7 and claim 24 allows for R, H, K, D or E to be at position 7. Thus, the sequence of claim 24 broadens the scope of instant claim 18 which requires E at position 7. For examination purposes, claim 24 will be interpreted as being dependent on claim 19.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claim(s) 18-29, 33 are rejected under 35 U.S.C. 103 as being unpatentable over Chen (WO2018165655 A1, cited in Applicant’s IDS) in view of Summerton (US20060193775 A1, cited in Applicant’s IDS).
Regarding claim 24, there is a rejection under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends (see above rejection). For examination purposes, claim 24 will be interpreted as being dependent on claim 19 and thus is a peptide consisting of SEQ ID NO:38 (excluding SEQ ID Nos:29 or 33).
Chen teaches a peptide comprising the sequence GLLDLLKLLLKAAG (see SEQ I DNO:3, Table 1, referred to as LDKA) which falls within the scope of instant SEQ ID NO:38 and a peptide consisting of SEQ ID NO:38. Chen teaches that these peptides are membrane active, pore forming antimicrobial leucine rich helix peptides (see abstract, see paragraph 0173, “higher helical peptides have better penetration into the membrane and further promote pore formation or membrane disruption”).
The peptide of Chen fails to meet the limitations of not comprising SEQ ID Nos:29 or 33 or comprising instant SEQ ID NO:39 as it does not teach a glutamic acid at position 7 (but rather a lysine or histidine).
However, Summerton teaches alpha helical embedder peptides designed to insert into membranes in acidic tumor environments. Summerton discloses glutamic acid pairs within alpha helical peptides. Summerton teaches that placement of glutamic acid residues within leucine rich helices modulate membrane insertion properties (see paragraphs 0046-0047). Summerton thus teaches structural design principle of placing glutamic acid residues in defined helical positions within leucine rich peptides to modulate membrane behavior.
It would have been obvious before the effective filing date of the claimed invention to substitute lysine or histidine at position 7 of Chen with glutamic acid in view of Summerton’s teaching that placement of glutamic acid within leucine rich alpha helical peptides modulates membrane insertion properties. Such modification constitutes a predictable substitution of one known charged residue for another within a known membrane active scaffold, with a reasonable expectation of similar pore forming activity (See MPEP 2143, simple substitution).
Furthermore, Chen expressly teaches that membrane selectivity and pore formation depend on hydrophobic movement, helicity and charged residue placement. Selecting among a finite set of charged amino acids (R, H, K, D, E) to tune these properties constitutes routine optimization of a known peptide.
Given Chen’s teaching that membrane activity depends on amphipathic helicity and charged residue placement, and Summerton’s teaching that glutamic acid placement predictably modulates membrane interaction, a person of ordinary skill would have reasonably expected the modified peptide to retain pore-forming activity.
Regarding instant SEQ ID NO:26 found in instant claims 20-22, Summerton teaches glutamic acid “acid pairs” (EE, EXXE, EXXXE) in alpha helical, leucine rich peptides, and emphasizes glutamic acid side chains forming the acid pair. Aspartic acid is chemically similar and substitution to glutamic acid isa predicable way to match “E-E” spacing in a helix. Swapping D for E is a conservative substation (both acidic) that predictably adjusts charge placement/helix amphipathicity. It would have been obvious before the effective filing date of the claimed invention to substitute aspartic acid at position 4 with glutamic acid in addition to substituting position 7 with glutamic acid, because Summerton teaches that glutamic acid residues positioned to form acid pair motifs in leucine rich alpha helical peptides modulate membrane insertion behavior. Replacing D with the closely related acidic residue E constitutes predictable variation/routine optimization to implement the taught glutamic acid pairing with a reasonable expectation of similar membrane active behavior (See MPEP 2143).
Thus, substitution of D at position 4 with E and substitution at position 7 with E in the peptide of Chen results in a peptide comprising/consisting of instant SEQ ID NO:26 which meets the limitations of instant claims 18-22 and 24.
Regarding claim 23, Chen teaches wherein there is a tryptophan residue at the C-terminus (see SEQ ID No:4 of Chen for example). Regarding claim 25, the peptides of Chen are all in L-form (see paragraph 0013, Table 1).
Regarding the functional limitations of “wherein the peptide forms an alpha helical assembly” (Claim 26) and “wherein the peptide forms a pore in a cancer cell membrane” (Claim 27), Chen in view of Summerton teaches the same peptides of the instant claims and thus, these properties would be inherent to the peptides.
Regarding claim 28, A kit for treating or preventing cancer comprising a pharmaceutically acceptable composition comprising the peptide of claim 18 and one or more pharmaceutically acceptable excipients, a kit is limited only the extent it recites structural components. Here, the kit includes the peptide composition and pharmaceutically acceptable excipients (which are taught by the prior art, see paragraph 0074). Thus, the kit is the same as a conventional pharmaceutical composition. The recited purpose “for treating or preventing cancer” and breast cancer (Claim 29) is an intended use and does not distinguish over the prior art structure.
Please note that it is regarded that "intended use" of a composition or product will not further limit claims drawn to a composition or product. See, e.g., Ex parte Masham, 2 USPQ2d 1647 (1987) and In Re Hack 114, USPQ 161. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim limitation.
Claim(s) 18-30, 33 are rejected under 35 U.S.C. 103 as being unpatentable over Chen (WO2018165655 A1) in view of Summerton (US20060193775 A1) as applied to claims 18-29, 33 above, in further view of Bolkent (WO2016099409 A1, cited in Applicant’s IDS).
The teachings of Chen in view of Summerton are described in the above rejection. Chen in view of Summerton do not specifically teach the peptides used for treating cancer in combination with a chemotherapeutic.
However, Bolkent teaches of pharmaceutical formulations comprising antimicrobial peptides for inducing pore formation on the cell surface of breast cancer cells (see pages 15-16). Bolkent additionally teaches co-administration with chemotherapeutic agents (see page 18, first paragraph).
Although Chen teaches membrane active peptides in the context of microbial infection, Chen teaches that he peptides function by forming pores in cellular membranes through alpha helical structure and charge distribution. Bolkent teaches that antimicrobial pore forming peptides exhibit anticancer activity by disrupting cancer cell membranes. Summerton further teaches that glutamic acid placement within leucine rich alpha helical peptides promotes membrane embedding in acidic tumor environments. Because both microbial and cancer cell membranes share susceptibility to amphipathic membrane disruptive peptides, a person of ordinary skill in the art would have been motivated to apply Chen in view of Summerton’s peptides to cancer treatment. Such application represents the predictable use of a prior art element according to its established function (See MPEP 2143).
Furthermore, it would have been obvious to use the peptides of Chen in view of Summerton for treating cancer. One of ordinary skill in the art would have been motivated to apply Chen in view of Summerton’s membrane disruptive peptide to cancer therapy because Bolkent teaches that antimicrobial pore forming peptides exhibit anti-cancer activity through membrane disruption of cancer cells. There is a reasonable expectation of success because Chen teaches that its peptides disrupt cell membranes via helix formation and Bolkent teaches that cancer cell membranes are susceptible to disruption by AMP peptides, indicating that peptides working via this mechanism can be cytotoxic on cancer cells.
Furthermore, it would have been obvious to include a chemotherapeutic agent in combination with the membrane disrupting peptide. One of ordinary skill in the art would have been motivated to include a chemotherapeutic agent because Bolkent teaches that membrane disruptive peptides may be combined with conventional chemotherapeutic agents to enhance anticancer activity. There would have been a reasonable expectation of success because increasing membrane permeability through pore formation enhances intracellular delivery and cytotoxic effect of chemotherapeutic agents. Thus, instant claim 30 is rendered obvious in view of Chen, Summerton and Bolkent.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 18-30, 33 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of US Patent No. 11059855 B2(reference application) in view of Summerton (US20060193775 A1) as applied to claims 18-29 above, in further view of Bolkent (WO2016099409 A1).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application claims “peptide having a sequence comprising the motif GLLxLLELLLxAAG (SEQ ID NO: 39), wherein each x is independently selected from arginine (R), histidine (H), lysine (K), aspartic acid (D) or glutamic acid (E)” (claim 18). The instant application further claims SEQ ID NO:39 (see claim 19); instant SEQ ID NO:26 (claim 21); L form (Claim 25); a kit comprising the peptide and excipient (Claim 28); a chemotherapeutic agent (Claim 30).
US Patent No. 11059855 claims A pore forming peptide comprising GLLDLLKLLLKAAG and GLLDLLHLLLKAAGW (see claim 1). US Patent No. 11059855 further claims the peptides in a pharmaceutical formulation (see claims 6-7) and an additional agent (Claim 8). US Patent No. 11059855 is silent to
The peptide of US Patent No. ‘855 fails to meet the limitations of not comprising SEQ ID Nos:29 or 33 or comprising instant SEQ ID NO:39 as it does not teach a glutamic acid at position 7 (but rather a lysine or histidine).
However, Summerton teaches alpha helical embedder peptides designed to insert into membranes in acidic tumor environments. Summerton discloses glutamic acid pairs within alpha helical peptides. Summerton teaches that placement of glutamic acid residues within leucine rich helices modulate membrane insertion properties (see paragraphs 0046-0047). Summerton thus teaches structural design principle of placing glutamic acid residues in defined helical positions within leucine rich peptides to modulate membrane behavior.
It would have been obvious before the effective filing date of the claimed invention to substitute lysine or histidine at position 7 of US Patent No. ‘855 with glutamic acid in view of Summerton’s teaching that placement of glutamic acid within leucine rich alpha helical peptides modulates membrane insertion properties. Such modification constitutes a predictable substitution of one known charged residue for another within a known membrane active scaffold, with a reasonable expectation of similar pore forming activity (See MPEP 2143, simple substitution).
Furthermore, selecting among a finite set of charged amino acids (R, H, K, D, E) to tune these properties constitutes routine optimization of a known peptide (pore forming properties).
Regarding instant SEQ ID NO:26 found in instant claims 20-22, Summerton teaches glutamic acid “acid pairs” (EE, EXXE, EXXXE) in alpha helical, leucine rich peptides, and emphasizes glutamic acid side chains forming the acid pair. Aspartic acid is chemically similar and substitution to glutamic acid isa predicable way to match “E-E” spacing in a helix. Swapping D for E is a conservative substation (both acidic) that predictably adjusts charge placement/helix amphipathicity. It would have been obvious before the effective filing date of the claimed invention to substitute aspartic acid at position 4 with glutamic acid in addition to substituting position 7 with glutamic acid, because Summerton teaches that glutamic acid residues positioned to form acid pair motifs in leucine rich alpha helical peptides modulate membrane insertion behavior. Replacing D with the closely related acidic residue E constitutes predictable variation/routine optimization to implement the taught glutamic acid pairing with a reasonable expectation of similar membrane active behavior (See MPEP 2143).
Thus, substitution of D at position 4 with E and substitution at position 7 with E in the peptide of US Patent No. ‘855 results in a peptide comprising instant SEQ ID NO:26.
Regarding claim 25, the peptides of US Patent No. ‘855 are all in L-form (see paragraph 0013, Table 1).
Regarding the functional limitations of “wherein the peptide forms an alpha helical assembly” (Claim 26) and “wherein the peptide forms a pore in a cancer cell membrane” (Claim 27), US Patent No. ‘855in view of Summerton teaches the same peptides of the instant claims and thus, these properties would be inherent to the peptides.
Regarding claim 28, A kit for treating or preventing cancer comprising a pharmaceutically acceptable composition comprising the peptide of claim 18 and one or more pharmaceutically acceptable excipients, a kit is limited only the extent it recites structural components. Here, the kit includes the peptide composition and pharmaceutically acceptable excipients (which are taught by the prior art, see paragraph 0074). Thus, the kit is the same as a conventional pharmaceutical composition. The recited purpose “for treating or preventing cancer” and breast cancer (Claim 29) is an intended use and does not distinguish over the prior art structure.
Please note that it is regarded that "intended use" of a composition or product will not further limit claims drawn to a composition or product. See, e.g., Ex parte Masham, 2 USPQ2d 1647 (1987) and In Re Hack 114, USPQ 161. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim limitation.
US Patent No. ‘855 in view of Summerton does not specifically teach the peptides used for treating cancer in combination with a chemotherapeutic.
Bolkent teaches of pharmaceutical formulations comprising antimicrobial peptides for inducing pore formation on the cell surface of breast cancer cells (see pages 15-16). Bolkent additionally teaches co-administration with chemotherapeutic agents (see page 18, first paragraph).
Although US Patent No. ‘855 claims membrane active peptides in the context of microbial infection, US Patent No. ‘855 claims that the peptides function by forming pores in cellular membranes (see claim 1). Bolkent teaches that antimicrobial pore forming peptides exhibit anticancer activity by disrupting cancer cell membranes. Summerton further teaches that glutamic acid placement within leucine rich alpha helical peptides promotes membrane embedding in acidic tumor environments. Because both microbial and cancer cell membranes share susceptibility to amphipathic membrane disruptive peptides, a person of ordinary skill in the art would have been motivated to apply US Patent No. ‘855 in view of Summerton’s peptides to cancer treatment. Such application represents the predictable use of a prior art element according to its established function (See MPEP 2143).
Furthermore, it would have been obvious to use the peptides Us Patent No. ‘855 in view of Summerton for treating cancer. One of ordinary skill in the art would have been motivated to apply Us Patent No. ‘855 in view of Summerton’s membrane disruptive peptide to cancer therapy because Bolkent teaches that antimicrobial pore forming peptides exhibit anti-cancer activity through membrane disruption of cancer cells. There is a reasonable expectation of success because Us Patent No. ‘855 claims membrane pore forming properties and Bolkent teaches that cancer cell membranes are susceptible to disruption by AMP peptides, indicating that peptides working via this mechanism can be cytotoxic on cancer cells.
Furthermore, it would have been obvious to include a chemotherapeutic agent in combination with the membrane disrupting peptide. One of ordinary skill in the art would have been motivated to include a chemotherapeutic agent because Bolkent teaches that membrane disruptive peptides may be combined with conventional chemotherapeutic agents to enhance anticancer activity. There would have been a reasonable expectation of success because increasing membrane permeability through pore formation enhances intracellular delivery and cytotoxic effect of chemotherapeutic agents.
Claims 18-30, 33 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15, 26-30 of Copending Application No. 18030996 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application claims “peptide having a sequence comprising the motif GLLxLLELLLxAAG (SEQ ID NO: 39), wherein each x is independently selected from arginine (R), histidine (H), lysine (K), aspartic acid (D) or glutamic acid (E)” (claim 18). The instant application further claims SEQ ID NO:39 (see claim 19); instant SEQ ID NO:26 (claim 21); L form (Claim 25); a kit comprising the peptide and excipient (Claim 28); a chemotherapeutic agent (Claim 30).
Copending Application No. 18030996 claims “A nanoparticle comprising one or more peptides having a sequence comprising the motif GLLxLLxLLLxAAG, wherein each x is independently selected from arginine (R), histidine (H), lysine (K), aspartic acid (D) or glutamic acid (E)” (claim 1) which overlaps with the instant claims peptide. Copending Application No. 18030996 further claims wherein the motif is GLLxLLELLLxAAG (Claim 2); the same sequences of the instant claims (see claims 5-6); consisting language (claim 9); L form (claim 11); treating cancer (claim 27); additionally comprising chemotherapeutic agent (Claim 28); tryptophan at the C-terminus (claim 30). Regarding instant claim 28, A kit for treating or preventing cancer comprising a pharmaceutically acceptable composition comprising the peptide of claim 18 and one or more pharmaceutically acceptable excipients, a kit is limited only the extent it recites structural components. Here, the kit includes the peptide composition and pharmaceutically acceptable excipients (which are taught by the prior art, see paragraph 0074). Thus, the kit is the same as a conventional pharmaceutical composition. The recited purpose “for treating or preventing cancer” and breast cancer (Claim 29) is an intended use and does not distinguish over the prior art structure. Copending Application No. 18030996 teaches the same formulation comprising the peptide and a chemotherapeutic agent, thus meeting the limitations of the claim.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
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/ERINNE R DABKOWSKI/ Examiner, Art Unit 1654