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 .
Status of Claims/Rejections
Claims 26-28, 30-33, 37-41 and 43-44 were amended. Claims 34-36 were cancelled and new claims 45-50 were added. Based on the amendments and argument, applicants have shown that the ETDA showed an unexpected result, rendering claim 27 novel and unobvious over the art. Additionally, applicants amendments and remarks regarding the claimed percentages were persuasive in that there must be a result effective variable from which to optimize the concentration. The prior art is silent as to the concentration in weight percentage, which is not provided in convertible units because the prior art is silent as to the injection volume. As such, claims 26-28, 30-33, 37-40 are novel and unobvious over the prior art.
The non-statutory double patenting rejection is withdrawn for the same reasons as the 103(a) rejection, as there is no result effective variable.
As to claims 41, 42, 47 and 48, the amendments to claims 41 and 47 do not overcome the enablement rejection, as will be discussed below. Additionally, amended claim 38 is now dependent on amended claim 27, which raises an additional 112 (B) rejection that will be discussed below. An Office action on the merits follows.
Objections
Claims 43-46, 49 and 50 objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim Rejections 35 USC 112(A)
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.
Claims 41, 42, 47 and 48 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 treating wounds and bacterial infection and inflammation with SEQ ID NOs: 1-7, this does not reasonably provide enablement for any peptide of the sequence X1-X2-X3-X4-X5-X6-W-X8-X9-X10 with broad variations in the genus of claim 26. 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 use the invention commensurate in scope with these claims.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue." These factors include, but are not limited to:
(1) The breadth of the claims; (2) The nature of the invention; (3) The state of the prior art; (4) The level of one of ordinary skill; (5) The level of predictability in the art; (6) The amount of direction provided by the inventor; (7) The existence of working examples; and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988) (reversing the PTO's determination that claims directed to methods for detection of hepatitis B surface antigens did not satisfy the enablement requirement). In Wands, the court noted that there was no disagreement as to the facts, but merely a disagreement as to the interpretation of the data and the conclusion to be made from the facts. In re Wands, 858 F.2d at 736-40, 8 USPQ2d at 1403-07. The Court held that the specification was enabling with respect to the claims at issue and found that "there was considerable direction and guidance" in the specification; there was "a high level of skill in the art at the time the application was filed;" and "all of the methods needed to practice the invention were well known." 858 F.2d at 740, 8 USPQ2d at 1406. After considering all the factors related to the enablement issue, the court concluded that "it would not require undue experimentation to obtain antibodies needed to practice the claimed invention." Id., 8 USPQ2d at 1407.
(1) The nature of the invention and (5) The breadth of the claims:
The invention is drawn to a method of treating a disorder in an individual in need thereof, wherein the method comprises administering an effective amount of a composition comprising a compound comprising SEQ ID NOs: 1-7. Claims 41 and 47 and the specification do not carve out a patient class of those “in need thereof,” to enable the scope of disorders treatable with the claimed SEQ ID NOs: 1-7. The nature of the invention requires a supported disorder or group of disorders that are known or supported in the specification or the art to be treatable with the claimed peptides.
(2) The state of the prior art:
As to treating any disorder in a subject “in need thereof,”, it is widely known that there is no one drug that can effectively treat any disorder, as many disorders, such as chronic genetic defects, or certain cancers, are not treatable with any drug, let alone all of the peptides claims.
The specification does state that previous studies have addressed structure function relationships of TCP-25 and its bioactive epitopes. For example, HVF18 (HVFRLKKWIQKVIDQFGE)(SEQ ID NO:4) is present in wound fluids in vivo. The antibacterial and LPS binding epitope of TCP-25 is also present in GKY20 (GKYGFYTHVFRLKKWIQKVI) (SEQ ID NO 3), which contains the first 20 amino acids of TCP-25. Similar to TCP-25, both of these peptides were shown to exert dual antibacterial and anti-inflammatory effects (p. 74). However, these studies do not encompass the peptide therapeutic art as a whole, which has significant impediments to treating diseases and disorders. A review of the current applications and future directions of peptide pharmaceuticals highlights these drawbacks, which include membrane permeability, which depends on multiple factors, including peptide length and amino acid composition (Wang et al., Signal Transduction and Targeted Therapy (2022) 7:48; spanning p. 3-4).
Peptides are generally unable to cross the cell membrane to target intracellular targets, which limits their applications in drug development to more extracellular targets. Lau et al. reported in 2018 that >90% of peptides in active clinical development targeted extracellular targets, including G-protein coupled receptors (GPCRs), gonadotropin-releasing hormone (GnRH) receptor, Glucagon-like peptide 1 (GLP-1) receptor (Bioorganic and Medicinal Chemistry. Vol. 26, Issue 10, 1 June 2018, Pages 2700-2707).
In addition to their inability to cross cellular membranes, peptides have poor in vivo stability. Natural peptides consist of chains of amino acids joined by amide bonds, which can be easily hydrolyzed or destroyed by enzymes in vivo, upon exposure to the environment, without any protection. These inherent chemical properties make the peptides chemically and physically unstable, with a short half-life and fast elimination in vivo (Wang, p. 4). Peptides that are not rationally designed to have the stability conferred by secondary or tertiary structures will not only have difficulty with biostability, but they also bind to their targets via protein-protein interactions, which is determined by the properties that the side chains and their substitutions affect their secondary structure, including turns, helices, hairpins, and extended conformations (Wang, p. 6).
These difficulties in making and using peptide pharmaceuticals for treating disorders are widely recognized in the art and provide roadblocks for treating most disorders without significant guidance and examples.
(3) The relative skill of those in the art:
The relative skill of those in the art is high.
(4) The predictability or unpredictability of the art:
Applicant’s claims are drawn to treating any disorder in a subject with SEQ ID NOs: 1-7. However, the claims do not identify the patient population; therefore, the claims imply that any subject can be “in need thereof,” as claims 41 and 47 do describe a patient class, and claims 42 and 48 are extremely broad, in that they do not describe any class of disorders, making the subjects to which the peptide should be administered highly unpredictable.
(6) The amount of direction or guidance presented and (7) The presence or absence of working examples:
The specification has not provided clear guidance as to how to determine the patient population or clear guidance as to which structural features and characteristics of the peptides of claims 26-28 are needed for any subject “in need thereof,” to be “therapeutically effective.”
There is no guidance as to how much of the compound is needed for treatment of a disorder for any intended therapeutic use, as there is no therapeutic dosage because the claims are drawn to the amount in the composition. Without a clearly defined patient class or any therapeutic parameters for dosage, symptoms, etiology or therapeutic effects in a defined patient class, the scope of “in need thereof” is not supported by the examples of the specification.
(8) The quantity of experimentation necessary:
Because it is uncertain to predict the patient population would be “in need thereof,” or which peptides of the genus of claimed compounds would treat the scope of any disorder or condition, one of ordinary skill in the art would be burdened with undue “painstaking experimentation study” to determine how to make and use the invention commensurate with the scope claimed.
Response to Arguments
Applicant's arguments and amendments filed 02/23/26 have been fully considered but they are not persuasive.
Applicants have amended the claims to reflect only the supported peptide sequences, SEQ ID NOs: 1-7. However, the clams have not been amended to specific the patient class as anything as broad as “in need thereof,” which does not enable the method of treatment for anything beyond what is supported by examples and generally known in the art as a disorder to be treated with thrombin peptides. “A disorder of the skin, eyes, ears or nose” can be as broad as treating (for example) skin cancer, glaucoma, hearing loss, etc. as there are no clear definition in the specification of what “in need thereof” includes, leaving the disorder open to any patient class.
As such, the claims are not enable for treating any disorder generally with SEQ ID NOs: 1-7.
Claim Rejections 35 USC 112(D)
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 38 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 38 recites a pH of “at most 8, or lower than 7, or lower than 6, or 5.5 or lower, and/or wherein the pH is higher than 3, or at least 3.5.
This allows for alternatives that cover the entire pH range because they can be anything lower than 8 or anything higher than 3, which does not further limit the claim.
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.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANETTE M LIEB whose telephone number is (571)270-3490. The examiner can normally be reached M-F 10-7.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko Garyu can be reached at 571-270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JEANETTE M LIEB/Primary Examiner, Art Unit 1654
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