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 .
Status of the Application
The claims of 26 April 2023 are entered.
The election of 20 November 2025 is entered.
Claims 1-20 are pending. Claims 1-8 and 17-20 are withdrawn without traverse. Claims 9-16 are being examined on the merits.
Election/Restrictions
Applicant’s election without traverse of Group IV (claims 9-16) in the reply filed on 20 November 2025 is acknowledged.
Claims 1-8 and 17-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 20 November 2025.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/335,130, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The claims are drawn to a method of treating a subject having a disease or condition characterized by excess matrix deposition or fibrosis, the method comprising administration of a composition comprising a polypeptide consisting of VRPLQELCRQRIVAAVGRENLARIPLNPVLRDYLSSFPFQI. This sequence is not explicitly disclosed in the ‘130 provisional application. While a haec verba recitation of a claim limitation is not expressly required to satisfy 35 U.S.C. 112(a), the Examiner does not find any implicit support for the claimed subject matter.
The ‘130 application discusses only that “…a 40 amino acid conserved region within the SOCS (suppressors of cytokine signaling) family of proteins called the SOCS domain degrades the fibronectin and collagen matrix in myofibroblast cells, thereby reversing the myofibroblast disease markers towards normal fibroblast lung cells”. This language does not lead to the claimed sequence, as at best it discloses a genus of peptides but not explicit guidance or disclosure on what specific residues constitute the 40 amino acid region. In this case, the skilled artisan is left with a genus but no particular guidance or markers as to what species are relevant. The skilled artisan could not have reasonably found implicit support in the ‘130 application for the instantly claimed subject matter. Therefore, priority to the ‘130 application is denied, with the earliest effective filing date afforded for the claims being 26 April 2023.
Claim Objections
Claim 14 is objected to because of the following informalities: VHL should be defined at its first usage. Appropriate correction is required.
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 9, 10, and 13-16 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 treating a subject having pulmonary fibrosis, does not reasonably provide enablement for a method of treating a subject having a disease or conditions characterized by excess matrix deposition or fibrosis. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
“[T]o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation.’” Genentech Inc. v. Novo Nordisk 108 F.3d 1361, 1365, 42 USPQ2d 1001, 1004 (Fed. Cir. 1997); In re Wright 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); See also Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 1212, 18 USPQ2d 1016, 1026 (Fed. Cir. 1991); In re Fisher 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). Further, in In re Wands 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988) the court stated:
Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman [230 USPQ 546, 547 (BdPatAppInt 1986)]. 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 unpredict-ability of the art, and (8) the breadth of the claims.
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).
Nature of the Invention
The invention is drawn to administration of a composition comprising a SOCS box protein of sequence VRPLQELCRQRIVAAVGRENLARIPLNPVLRDYLSSFPFQI. Administration is claimed to treat a subject who has a disease or condition characterized by excess matrix deposition or fibrosis.
Breadth of the Claims
The composition is narrowly claimed. The method claims a broad genus of diseases or conditions.
State of the Prior Art
The prior art recognizes a variety of human fibrotic diseases of varying etiologies.
Rosenbloom et al. (Methods Mol. Biol. 1627:1-23, published 2017) discuss various fibrotic diseases and note that causative mechanisms for fibrosis can be diverse (see e.g. p.2). Rosenbloom also notes that fibrotic diseases can target a number of organs (see e.g. Table 1). Highly different mechanisms can result in fibrosis including myofibroblast activation, TFG-β pathways, bone morphogenic protein signaling, oxidative stress, and others (see e.g. Sections 2-5). Rosenbloom notes that the complexity of the fibrotic pathways makes development of anti-fibrotic therapies difficult (see e.g. Section 6.2).
Zhao et al. (Signal Transduction and Therapy 7:206) notes that “The high mortality and complex pathogenesis of fibrotic diseases pose great challenges in clinical therapy. Various cells and signaling pathways are involved in the progression of fibrosis. Drugs targeting these abnormal pathways are constantly being developed, and most of them demonstrate good anti-fibrotic activity in clinical trials. However, the side effects of these drugs often lead to drug discontinuation”. Zhao further reinforces that the art considered treatment of fibrosis challenging at best.
Relative Skill of those in the Art
The relative skill of those in the art is high. However, it is not within the skill of those in the art to prepare a single composition that treats all manners of diseases or conditions marked by excess matrix deposition or fibrosis.
Predictability or Unpredictability of the Art
There is a general lack of predictability in the pharmaceutical art. In re Fisher, 427, F. 2d 833, 166, USPQ 18 (CCPA 1970).
As noted above, the prior art also reflects unpredictability in noting the challenges in developing anti-fibrotic drugs.
Amount of Direction or Guidance Given
The guidance on fibrosis focuses on pulmonary fibrosis. No other forms of fibrosis are discussed. A model using differentiation of fibroblasts to myofibroblasts are used in vitro but not specifically correlated to forms of fibrosis other than pulmonary fibrosis. Notably, the only fibroblasts utilized were lung fibroblasts.
Presence/Absence of Working Examples
The working examples concern differentiation of lung fibroblasts to myofibroblasts and a mouse model of idiopathic pulmonary fibrosis. No other forms of fibrosis are studied or discussed in the working examples.
Quantity of Experimentation Necessary
While it would not take any unnecessary experimentation to prepare the claimed 40 amino acid-long peptide of claim 1, applying it in a generic manner to any disease or condition characterized by excess matrix deposition or fibrosis would involve undue experimentation.
The Applicants have provided a single peptide and asserted a broad link between application of it and treatment of any disease or condition marked by excess matrix deposition or fibrosis. Yet the only examples show that the focus is solely on pulmonary fibrosis. The only actual examples of in vivo usage require a murine model of bleomycin-induced idiopathic pulmonary fibrosis.
In this case, there are no other models provided or discussed for other diseases or conditions marked by excess matrix deposition or fibrosis. The onus is solely on the skilled artisan to handle all experimentation for a broad genus of treatment. Such a level of experimentation is undue.
In view of the Wands factors as discussed above, it is the Examiner’s opinion that the claims are not fully enabled and one of skill in the art would have to engage in undue experimentation to practice the invention as claimed herein, without a reasonable assurance of success.
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 9-16 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.
In claim 9, the claim is indefinite because it is linked to claim 1 and requires the administration of a composition comprising SEQ ID NO: 1, which is amenable to multiple plausible interpretations: claim 1 recites “A composition comprising a polypeptide consisting of the following amino acid sequence VRPLQELCRQRIVAAVGRENLARIPLNPVLRDYLSSFPFQI (SEQ ID NO: 1)”. This language is directed to a 40-amino acid long peptide. However, an examination of SEQ ID NO: 1 indicates that it is a 213 amino acid-long peptide. The skilled artisan could interpret the method as requiring the 213 amino acid-long peptide of SEQ ID NO: 1 but also could interpret the claim as requiring only the 40 amino acid-long peptide recited in claim 1. Ex parte Kenichi Miyazaki, 89 USPQ2d 1207, 1211 (BPAI 2008) (precedential) “hold[s] that if a claim is amenable to two or more plausible constructions, the USPTO is justified in requiring the applicant to more precisely define the metes and bounds of the claimed invention by holding the claim unpatentable under 35 U.S.C. § 112, second paragraph, as indefinite.” The dependent claims do not remedy this deficiency with respect to the amino acid sequence utilized in the method of treatment.
For the purposes of prior art, the Examiner will interpret the composition as used in the method of treatment as requiring the 40 amino acid long sequence as found in claim 1. If the Applicant intends to claim the peptide as recited in claim 1, then a corrected sequence listing is required limiting the recited sequence in SEQ ID NO: 1 to match that which is claimed.
With respect to claim 13, the term “hydroxyproline production of fibroblasts in the subject” is indefinite because the language implies that hydroxyproline production results in fibroblasts, rather than fibroblasts resulting in lower hydroxyproline production.
For the purposes of prior art, the Examiner interprets the claim as such that fibroblasts have reduced hydroxyproline production.
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.
Claims 9-13, 15, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Nakashima et al. (J. Allergy Clin. Immunol. 121:1269-1276, published May 2008, as cited on IDS of 5 July 2023, hereafter referred to as Nakashima) and Piganis et al. (J. Biol. Chem. 286:33811-33818, published September 2011, as cited on IDS of 5 July 2023, hereafter referred to as Piganis).
Nakashima discloses that SOCS1 is useful for inhibition of pulmonary fibrosis (see e.g. Figures 3 and 5). Nakashima discloses that decreased SOCS1 expression relates to increased pulmonary fibrosis in animal and human subjects, and should serve as a target for treatment of lung fibrosis (see e.g. p.1276 Col.1).
The difference between Nakashima and the claimed invention is that it does not disclose the 40 amino acid-long fragment as found in claim 1.
Piganis discloses that the SOCS box of SOCS1 is responsible for inhibition of type I interferon signaling, leading to the 40 amino acid-long sequence of claim 1 (see e.g. Figure 1). It is also noted that the Applicants admit Piganis discloses the same fragment (see e.g. p.3 lines 10-13 of the specification).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized the SOCS box fragment of Piganis as being shown as a minimal fragment in place of full-length SOCS1 as used in Nakashima to treat pulmonary fibrosis. The rationale comes from Nakashima showing full-length SOCS1 usage to treat pulmonary fibrosis and Piganis showing it as an effective minimal fragment. There would have been a reasonable expectation of success because the Piganis fragment still maintained interferon disrupting activity even in deleted form, such that one of ordinary skill in the art would have expected it to maintain activity when substituted for the full-length protein of Nakashima. The invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
With respect to claim 10, Nakashima discloses intranasal administration of an adenoviral vector to express exogenous SOCS1 (see e.g. p.1270 Col.1). It reasonably follows that one of ordinary skill in the art would follow a similar administration route for the fragment of Piganis since the goal is treatment of pulmonary fibrosis.
With respect to claim 11, as set forth above pulmonary fibrosis is disclosed by Nakashima.
With respect to claim 12, the Nakashima art shows that SOCS1 expression was significantly lower in idiopathic pulmonary fibrosis lung tissue samples, suggesting usage for that disease.
With respect to claim 13, Nakashima discloses that exogenous SOCS1 results in lower hydroxyproline (see e.g. Figure 6).
With respect to claim 15, as discussed above fibrosis is reduced per Nakashima.
With respect to claim 16, by necessity a reduction in pulmonary fibrosis results in restricted fibronectin matrix formation in the subject.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZACHARY J MIKNIS whose telephone number is (571)272-7008. The examiner can normally be reached M-F 9-5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached at (571) 270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ZACHARY J MIKNIS/Patent Examiner, Art Unit 1658