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
This application filed 03/07/2024 is a National Stage entry of PCT/EP2022/074974 , International Filing Date: 09/08/2022, claims foreign priority to 102021000023357, filed 09/09/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/07/2024, 01/21/2026 and 05/20/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Status
The claim listing filed 03/07/2024 is pending. Claims 1, 3, 4, 5, 6, 9, 10 are currently amended. Claim 2 is cancelled. Claims 1, 3-13 are pending and under examination.
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, 4, 5 and 11 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 a method of treating pathological angiogenesis, does not reasonably provide enablement for treating a disorder. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims. This is a scope of enablement rejection.
Claim 1 is directed to a method of treating a disorder. Embodiments of the specification disclose treating to encompass treatment of diseases resulting from pathological angiogenesis (See page 9, 5th paragraph).
Claim 3 is directed to the disorders, which include tumor, chronic inflammation, neo-vascularization disorder.
Claim 11 is directed to peptides, in the method of treatment.
While the instant specification is enabling for a method of treatment comprising administering the peptide, and reducing pathological angiogenesis associated with a tumor or neo vascularization or chronic inflammation, as demonstrated in experimental models in Fig 1-5 and in Examples 1-5, the specification is not enabling for broadly treating a disorder resulting from pathological angiogenesis, as recited in claim 1. Pathological angiogenesis affects not only the tumor but also the crosstalk between pathological angiogenesis and inflammation in different tissues with major focus on the brain, liver, and the lung during several organ-specific diseases (see conclusion -Jeong, JH., Ojha, U. & Lee, Y.M. Pathological angiogenesis and inflammation in tissues. Arch. Pharm. Res. 44, 1–15 (2021)). As such, claim 1, claims too broadly, the breadth of disorders associated with angiogenesis. Claim 3 recites tumor, chronic inflammation or neo-vascularization which encompass multiple histologic origins for the disorders, as noted in the crosstalk between pathological angiogenesis in different tissues (Jeong, JH., Ojha, U. & Lee, Y.M. Pathological angiogenesis and inflammation in tissues. Arch. Pharm. Res. 44, 1–15 (2021). Evidently, the specification is not enabling for treatment of a disorder broadly, in a subject population requiring the method of treatment.
As stated in § MPEP 2164.01(a), “there are many factors to consider when determining whether
there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement
requirement and whether any 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 skill in the art;
5.The level of predictability in the art;
6. The amount of direction provided by the inventor;
7. The presence or absence of working examples;
8. The quantity of experimentation needed to make or use the invention based on the
disclosure.
See in re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). The eight Wands
factors are applied to claims 1, 3, 4, 5, 11 as follows:
The breadth of the claims and the nature of the invention
Claims 1, 3, 4, 5 and 11 are directed to a method of treatment of a disorder comprising administering a peptide to a subject in need thereof. ‘Disorder’, as recited in claim 3, is a tumor, chronic inflammation or neo-vascularization. The specification does not provide a special definition of treatment. Under a broadest reasonable interpretation (BRI), words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. In re Zietz, 893 F.2d 319, 321, 13 USPQ2d 1320, 1322 (Fed. Cir. 1989) (discussed below); Chef America, Inc. v. Lamb-Weston, Inc., 358 F.3d 1371, 1372, 69 USPQ2d 1857 (Fed. Cir. 2004). The ordinary and customary meaning of ‘treatment’ in the art, before the effectively filed date of the claimed invention is -to prevent, cure, ameliorate, or slow progression of a medical condition (See Merriam-Webster Dictionary). However, the specification does not provide enablement for treatment of a disorder broadly, wherein treatment encompasses prevention, cure, amelioration or slowed progression.
In Figs 1-5, and examples 1-5, the specification does provide evidence of a method of reduced tube formation upon treatment of HUVECs with a combination of pro-angiogenic molecules and peptide (i.e. pathological angiogenesis; see page 2, 2nd paragraph). Although the claims are enabling for a method of reducing pathological angiogenesis in a tumor associated with angiogenesis, chronic inflammation associated with pathological angiogenesis or neo vascularization associated with pathological angiogenesis, comprising administering to a subject in need thereof, the claims are unduly broad with respect to treating a disorder broadly.
The State of the Prior Art
It is noted that there is no prior art that teaches a method of treating a disorder broadly wherein as noted in Jeong, JH., Ojha, U. & Lee, Y.M. Pathological angiogenesis and inflammation in tissues. Arch. Pharm. Res. 44, 1–15 (2021), pathological angiogenesis affects several organ-specific diseases.
The Level of Skill in the Art
Practitioners in this art (physicians/immunologists/surgeons) would presumably
be highly skilled in the art for providing a method of treatment for the disorders as claimed.
The Level of Predictability in the Art
It is noted that the therapeutic art is unpredictable, requiring each embodiment to be
individually assessed for physiological activity. The amount of guidance or direction needed to enable
the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). This is because it
is not obvious from the disclosure, of a specific method of treatment of subject and alleviation of
symptoms. In the instant case, the specification provides tube formation data on HUVEC cell lines. The
specification does not demonstrate a subject suffering from a disorder (taking into account the breadth of disorders associated with pathological angiogenesis) and ensuing amelioration of the symptoms distinct to each of those disorders, after administering an effective amount of peptide, as claimed.
Without any experimentation demonstrating the claimed treatment, the level of unpredictability remains high. Therefore, it is unpredictable that the peptide composition will function in the treatment method as claimed.
The amount of Direction Provided by the Inventor and The Presence or Absence of
Working Examples
The instant specification does not provide adequate guidance with regard to the method of
treatment. Applicant’s limited disclosure is noted but is not sufficient to justify claiming the composition
broadly. Absent a reasonable a priori expectation of success for treating, one skilled in the art would have to extensively test the peptide composition, determine an effective dose on a subject
in need thereof, ascertain amelioration of symptoms, clinical outcome, etc. Since each prospective
embodiment, and indeed future embodiments as the art progresses, would have to be empirically
tested, and those which initially failed tested further, an undue amount of experimentation would be
required to practice the invention as it is claimed in its current scope, because the specification provides
inadequate guidance to do otherwise. The amount of direction or guidance presented in the
specification is very limited. As discussed in “[t]he Level of Predictability in the Art” section supra, the
specification teaches working examples of in vitro angiogenic assays with HUVEC cells treated with the peptide composition. There is no prior art that broadly teaches treatment of a disorder using the peptide composition, in a subject. Also, as noted in the “Breadth of the Claims and Nature of Invention” section, the specification does not provide evidence that a subject in need thereof is administered a
therapeutically effective amount or the amelioration of symptoms.
As such, the examples used in the specification are not indicative broadly of a method of
treatment with the desired result of amelioration of symptoms. It is further noted that Applicant
provides no data, examples, figures, etc. demonstrating a subject or an effective amount
for treatment. In the absence of such information, a person of ordinary skill in the art would reasonably
require undue quantity of experimentation.
Conclusion of Enablement Analysis 35 USC § 112(a)
MPEP § 2164.01(a), 4th paragraph states that “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).
After applying the Wands factors and analysis to claims 1, 3, 4, 5, 11, in view of the Applicant’s
entire disclosure, it is concluded that the practice of the invention as claimed in claims 1, 3, 4, 5, 11 would not be enabled by the written disclosure for treatment of a disorder. Therefore claims 1, 3, 4, 5, 11 are rejected under 35 U.S.C. §112(a) for failing to disclose sufficient information to enable a person of skill in the art to treat a subject as claimed.
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 7 and 8 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 7, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 8, the claim recites various routes of administration -oral, parenteral, etc. However, inhalation includes spray, powder or aerosol in parenthesis, with specific structural limitations. It is unclear if these are part of the group or if there is a structural requirement to meet the limitations of the claim.
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.
Claim(s) 1, 3-13 are rejected under 35 U.S.C. 103 as being unpatentable over Gattadahalli M. Anantharamaiah et al., hereinafter GM.A (Gattadahalli M. Anantharamaiah et al., US2011/0182992 A1; published Jul. 28, 2011).
Regarding claim 1, GM.A teaches, treatment of a condition (i.e. disorder) selected from a group consisting of cancer (i.e. tumor) (see page 27, last line), vascular condition characterized by an inflammatory response (i.e. neovascularization, chronic inflammation) [0023], etc, comprising administering to an individual diagnosed as having one or more symptoms of the various pathologies described ([0278], line 5; see Abstract). GM.A specifically teaches active agents (e.g. peptides) readily administered via an oral or intraocular injection (see Abstract). In Table 8 (page 62), GM.A teaches SEQ ID NO: 835: Boc-Glu-Asp-Arg-Tyr(tBu)-OtBu and SEQ ID NO: 905 (page 63): Fmoc-Try-Asp-Arg-Tyr-OtBu.
Examiner interprets, ‘comprising’ as open ended and therefore, the claim scope encompasses sequence DKY or DRY with any N/C terminal additions. Accordingly, the teaching in GM.A, of SEQ ID NO: 835 and SEQ ID NO: 905 are 100 % identical to the sequences as instantly claimed.
Notably, the claimed sequences are inherently met by the teachings of GM.A (see MPEP §2112.IV).
Regarding claim 3, GM.A teaches cancer (i.e. tumor) (see page 27, last line), vascular condition characterized by an inflammatory response (i.e. neovascularization, chronic inflammation) [0023], etc, comprising administering to an individual diagnosed as having one or more symptoms of the various pathologies described ([0278], line 5; see Abstract).
Regarding claim 4, GM.A teaches SEQ ID NO: 835 and SEQ ID NO: 905 of peptide length 4 amino acids (see Table 8, page 62-63).
Regarding claim 5, GM.A teaches particular protecting groups as noted in SEQ ID NO: 835 and SEQ ID NO: 905 (i.e. carboxyl) and that these groups may be substituted with other protecting groups or protecting groups can be eliminated [0196].
Regarding claim 6, GM.A teaches that peptides can, optionally, be mixed/combined with pharmacologically acceptable excipient. In certain embodiments the excipient is an excipient suitable for oral administration to a mammal [0022].
Regarding claim 7, GM.A teaches a concentration greater than about 4 mg/ml (i.e. 0.4 % by weight) ([0188], line 8).
Regarding claim 8, GM.A teaches administration via an oral route (see Abstract) and [0282] or via device [0288].
Regarding claim 9, Examiner interprets ‘group consisting of’ as a Markush group, presenting a closed set of alternatives. GM.A teaches that active agents are administered in conjunction with inhibitors, immunomodulators [0339].
Regarding claim 10, GM.A teaches SEQ ID NO: 835 and SEQ ID NO: 905, comprising sequence DRY, of length equal to or lower than 5 amino acids.
Regarding claim 11, GM.A teaches peptide comprising sequence DRY, as noted in the rejection for claim 10. Notably, GM.A teaches that four-mers can be represented by Formula I in which X1 and X4 are hydrophobic and/or bear hydrophobic protecting group(s) and X2 is acidic or basic while X3 is aliphatic or X2 is aliphatic while X3 is acidic or basic. The peptide can be all L-amino acids or include one, or more, or all D-amino acids [0198].
Regarding claim 12, the teaching of GM.A has been noted above.
Regarding claim 13, the teaching of GM.A has been noted above.
Conclusion
No claim is allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARCHANA VARADARAJ whose telephone number is (571)272-2366. The examiner can normally be reached Monday-Friday 10:00am-5:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached at 5712707430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ARCHANA VARADARAJ/ Examiner, Art Unit 1658
/Melissa L Fisher/ Supervisory Patent Examiner, Art Unit 1658
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