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 .
This is the First Office Action on the Merits of US 18/031251 filed on 04/11/2023 which is a 371 of PCT/EP2021/078534 filed on 10/14/2021 which claims foreign priority of EP 20306214.6 filed on 10/15/2020.
Claims 1-16 are pending and under examination.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," 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 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) 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") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) 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 of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows: Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
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 incorporation-by-reference paragraph, 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.
Information Disclosure Statement
The IDS filed on April 4, 2023 has been considered by the examiner.
Claim Objections
Claim 1 is objected to because of the following informalities: The abbreviated term “TG2” should be written in full-length (i.e., Transglutaminase 2) the first time it appears in the claims.. 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.
Claims 5 and 13 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.
Independent claim 5 recites the limitation "the subject" in line 2. There is insufficient antecedent basis for this limitation in the claim because there is no prior reference in the claim to a subject.
Regarding claim 13, the phrase "such as" (line 4) 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).
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 1-16 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 contacting a TG2 inhibitor being the ZDON tetrapeptide to epithelial tissue, in vitro, does not reasonably provide enablement for administering to patients the breadth of TG2 inhibitors encompassed by the claims or methods of making and using the nanoparticles as recited in the claims. 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.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (CA FC 1988). Wands states at page 1404,
“Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman. They 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.”
The nature of the invention and breadth of claims:
Claims 1-16 are drawn methods comprising administering a TG2 inhibitor to a patient having chronic airway disease. Claim 9 recites that the TG2 inhibitor is a small organic molecule or an antibody. Claim 10, recites that the TG2 inhibitor is an inhibitor of gene expression that is a siRNA, an antisense oligonucleotide or a ribozyme. Claim 13 recites nanoparticles for lung delivery which comprise certain drugs, such as gastro-intestinal drugs or vitamins, which would not appear to be suitable for intra-pulmonary administration, or to have any effect on the body following administration to the lung.
Claims are broad to the type of TG2 inhibitor and the type of administration.
The unpredictability of the art and the state of the prior art:
The invention is in a class of invention which the CAFC has characterized as “the unpredictable arts such as chemistry and biology.” Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
The state of the art teaches the unpredictability of lung treatments. For example, see EP 2 664 326 Al to Maiuri (published 11/20/2013; IDS ref); Kim et al Brit J of Pharmocology 2011 Vol162, pages 210-225; IDS ref) and US 20220040127 to Stanton et al.
Guidance in the Specification/Working Example:
The specification shows no working example of the presently claimed invention. The specification shows evidence that TG2 expression is involved in airway diseases and that respiratory mucins are TG2 substrates (See Figures 3-4). The specification provides in vitro testing data of the TG2 inhibitor ZDON. (See Fig5-6). Note that ZDON is a commercially available TG2 inhibitor which is a 6-diazo-5-oxo-norleucine tetrapeptide. The specification provides no other data of a different TG2 inhibitor. The specification provides no evidence that the broad scope of the claims are enabled. The specification provides no guidance for using a TG2 inhibitor being an antibody, a ribozyme, an antisense or an siRNA. The specification provides no example of a TG2-coated nanoparticle. The guidance provided by the specification amounts to an invitation for the skilled artisan to try and follow the disclosed instructions to make and use the claimed invention.
Quantity of Experimentation:
The quantity of experimentation in this area is extremely large since there is significant number of parameters which would have to be studied to enable the skilled artisan to practice the claimed invention as broadly as claimed. This would require significant inventive effort, with each of the many intervening steps, upon effective reduction to practice, not providing any guarantee of success in the succeeding steps.
Level of Skill in the Art:
The level of skill in the art is deemed to be high.
Undue Experimentation:
Given the broad claims in an art whose nature is identified as unpredictable, the unpredictability of that art, the large quantity of research required to define these unpredictable variables, the lack of guidance provided in the specification, the absence of a working example and the negative teachings in the prior art balanced only against the high skill level in the art, it is considered that it would require undue experimentation for one of skill in the art to perform the method of the claim as broadly written.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-7 and 9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by EP 2 664 326 Al to Maiuri (published 11/20/2013; IDS ref).
Regarding claim 1, Maiuri discloses administering to a patient having cystic fibrosis a therapeutically effective amount of a TG2 inhibitor. (See Title, Abstract, para 0014). Cystic fibrosis is a type of chronic airway disease (See instant claim 7). The treatment of cystic fibrosis includes improving mucociliary clearance, increasing the liquefaction of mucus, preventing mucus tethering to the airway wall, preventing extensive airway mucus plugging and/or preventing mucus occlusion of an airway lumen in the patient. (See para 002-005).
Regarding claim 2, Maiuri discloses a method of increasing the liquefaction of mucus in a patient suffering from cystic fibrosis, comprising administering to the subject a therapeutically effective amount of TG2 inhibitor. (See Title, Abstract; para 002-005, 0014).
Regarding claim 3, Maiuri discloses a method of preventing mucus tethering to the airway wall in a patient suffering from cystic fibrosis comprising administering to the subject a therapeutically effective amount of TG2 inhibitor. (See Title, Abstract; para 002-005).
Regarding claim 4, Maiuri discloses a method of preventing extensive airway mucus plugging in a patient suffering from cystic fibrosis comprising administering to the subject a therapeutically effective amount of TG2 inhibitor. (See Title, Abstract; para 002-005, 0014).
Regarding claim 5, Maiuri discloses a method of preventing mucus occlusion of an airway lumen comprising administering a therapeutically effective amount of TG2 inhibitor to a subject having cystic fibrosis (See Title, Abstract; para 002-005, 0014).
Regarding claim 6, Maiuri discloses that the patient has cystic fibrosis which is a chronic airway disease which causes abnormal or excessive viscoelasticity or cohesiveness of mucus. (See para 002-005, 0014).
Regarding claim 7, Maiuri discloses that the patient has cystic fibrosis (CF). (See Title, Abstract, 0014).
Regarding claim 9, Maiuri discloses that the TG2 inhibitor is a small organic molecule. (See para 0011, 0015).
Thus Mairui anticipates claims 1-7 and 9.
Claims 1-9 and 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ro et al (J. Allerg. Clin. Immunol. 2011, 127(2), AB61, Abs. 228; IDS ref) or Kim et al
Brit J of Pharmocology 2011 Vol162, pages 210-225; IDS ref). Kim et al is the Research Paper describing in detail the work of the Ro et al Abstract # 228).
Regarding claims 1-5, Ro et al discloses administering to a patient having asthma a therapeutically effective amount of a TG2 inhibitor. Asthma is a type of chronic airway disease (See instant claim 7). The treatment of asthma is construed to include improving mucociliary clearance, increasing the liquefaction of mucus, preventing mucus tethering to the airway wall, preventing extensive airway mucus plugging and/or preventing mucus occlusion of an airway lumen in the patient. (see Rationale, Methods, Results, Conclusions). See Kim et al entire article.
Regarding claim 6, Ro et al discloses that the patient has asthma which is a chronic airway disease which causes abnormal or excessive viscoelasticity or cohesiveness of mucus (see Rationale, Methods, Results, Conclusions).
Regarding claim 7, Ro et al discloses that the patient has asthma (see Rationale, Methods, Results, Conclusions).
Regarding claim 8, Ro et al discloses that the patient suffers from asthma (see Rationale, Methods, Results, Conclusions).
Regarding claim 9, Ro et al discloses that the TG2 inhibitor is an R2 peptide which meets the limitation of a small organic molecule (see Rationale/Methods/Results/Conclusions).
Regarding claim 16, Ro et al discloses that the asthma is severe asthma (see Rationale/Methods/Results/Conclusions.
Thus Ro et al anticipates claims 1-9 and 16.
Claims 1-7, 9, and 11-13, are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Stanton et al (published March 7, 2019).
Regarding claims 1-7, and 9, Stanton et al disclose administering the TG2 inhibitor cysteamine for use in treating cystic fibrosis which meets the limitations of claims 1-7. (See para 0101, 105, 0396 just below, 405, 412, 435, 542, 630, ref claim 25). Claim interpretation is provided above.
Stanton et al disclose use of nanoparticles to deliver therapeutic compounds useful for treating cysteamine sensitive diseases or disorders, and specifically cystic fibrosis (para 0101, 105, 0138, 0369, 0371, 0393,0395, 0396 just below, 405, 412, 435, 542, 630, ref claim 25). Stanton et al disclose that the route of administration is critical.
[0396] The present invention relates to novel compositions and methods useful for treating cysteamine sensitive diseases and disorders. Treatment entails oral administration of cysteamine precursors, convertible to cysteamine in the gastrointestinal tract. An important class of cysteamine precursors are mixed disulfides which, upon reduction in vivo, provide two thiols. Both thiols may be convertible to cysteamine in vivo, or just one. Cysteamine precursors in which both thiols are convertible to cysteamine are a preferred class of therapeutic agents for diseases including cystinosis, cystic fibrosis, malaria, and viral and bacterial infections. Non-limiting examples of such mixed disulfides include cysteamine-pantetheine and cysteamine-4-phosphopantetheine.
Regarding claims 11-13, Stanton et al discloses a method for treating cystic fibrosis using nanoparticles to carry the TG2 inhibitor cysteamine. Cysteamine meets the limitation of claims 11-13 of a therapeutic agent. Stanton et al does not disclose delivery directly to the lung but rather by a gastrointestinal route. Claims as presently written are construed to encompass such delivery since treating cystic fibrosis lung disease would require the therapeutic to be delivered to the lung. Stanton et al discloses nanoparticles in a patient in need thereof comprising administering the nanoparticles in combination with an amount of a TG2 inhibitor Stanton et al disclose nanoparticles comprising a TG2 inhibitor, including cysteamine, to enhance lung delivery in the treatment of cystic fibrosis.
Thus Stanton et al anticipates claims 1-7, 9, and 11-13.
Conclusion
No claim is allowed.
Related prior art which may be applied in a future office action:
WO-2014/124006 to Yu et al; IDS ref). Regarding claim 15, Yu et al discloses a “mucus-penetrating nanoparticle”. (See Abstract). In page 14, Yu et al disclose the nanoparticle is coated with a surface-altering agent. Yu et al does not recite coated with a TG2 inhibitor.
Olsen et al “Inhibition of Transglutaminase 2, a Novel Target for Pulmonary Fibrosis, by Two Small Electrophilic Molecules” (Am. J. Resp. Cell Mol. Biol. 2014, 50(4), pages 737-747; IDS ref). Regarding claims 1-5, Olsen et al discloses administering to a patient having Pulmonary Fibrosis a therapeutically effective amount of a TG2 inhibitor. Cystic fibrosis can result in pulmonary fibrosis. Cystic fibrosis is a type of chronic airway disease (See instant claim 7). The treatment of cystic fibrosis includes improving mucociliary clearance, increasing the liquefaction of mucus, preventing mucus tethering to the airway wall, preventing extensive airway mucus plugging and/or preventing mucus occlusion of an airway lumen in the patient. Regarding claims 6-7, Olsen et al discloses that the patient has cystic fibrosis which is a chronic airway disease which causes abnormal or excessive viscoelasticity or cohesiveness of mucus.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CATHERINE S HIBBERT whose telephone number is (571)270-3053. The examiner can normally be reached M-F 8:00-5:00.
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CATHERINE S. HIBBERT
Primary Examiner
Art Unit 1658
/CATHERINE S HIBBERT/Primary Examiner, Art Unit 1658