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 .
1. Claims 1-3, 5-10, 12-19, 22, 24 and 47 are pending in the instant patent application.
Claims 1-3, 5-10, 12-19, 22, 24 and 47 are under examination.
Claim Objections
2. Claim 6, 9, 24 and 27 are objected to because of the following informalities:
The claims recite “NBL1” without first providing the full name of the term. It is suggested that the term be spelled out at its first use and in all independent claims so that it is clearly understood what it stands for. Appropriate correction is suggested.
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.
3. Claims 3, 6-10, 12-16, 18 and 22 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.
4. Regarding claims 3 and 22, the phrase "such as" 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).
5. The term “inhibiting” in claims 6 and 9 is a relative term which renders the claim indefinite. The term “to inhibit” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Providing a point of reference or comparison within the claims would obviate this ground of rejection.
6. Regarding claims 7, 8 and 18, the phrase "e.g." renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
7. Claims 13-16 recite the limitation "contacting the fibrosis" in claim 1. There is insufficient antecedent basis for this limitation in the claims.
8. Claims 10 and 12 are indefinite for being dependent from indefinite claim.
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.
9. Claims 1-3, 5-10, 12-19, 22 and 24 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 methods of treating scar formation, fibrotic lung disease, or corneal wound by direct contact with or by administration to the site of the scar, to lung fibroblasts or corneal wound an effective amount of NBL1 protein, does not reasonably provide enablement for the full scope of the claimed methods. 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.
Claims 1-3, 5-10, 12-19, 22, 24 are directed to methods for preventing and treating fibrosis, adhesion formation, scar formation, fibrotic disease, specifically fibrotic lung disease, including pulmonary fibrosis, fibrotic interstitial lung disease, interstitial pneumonia, fibrotic variant of non-specific interstitial pneumonia, cystic fibrosis, lung fibrosis, chronic obstructive pulmonary lung disease, and pulmonary arterial hypertension, prevention and treatment of hepatic fibrosis, rheumatoid arthritis, congestive heart failure, chronic renal disease, Lyme disease, stromal fibrosis, uterine fibroids, ovarian fibrosis, corneal fibrosis, and scarring, all by administration of Neuroblastoma suppressor of tumorigenicity 1 (NBL1) protein, nucleic acid encoding NBL1 or a cell recombinantly altered to express NBL1. However, the specification does not provide sufficient guidance to enable practice the full scope of the claimed invention without undue experimentation.
The enablement requirement is met when one skilled in the art, having read the specification, could practice the invention without “undue experimentation.” Cephalon, Inc. v. Watson Pharm., Inc., 707 F.3d at 1336 (Fed. Cir. 2013). The factors to be considered in determining whether a disclosure would require undue experimentation 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, 8 USPQ2d, 1400 (CAFC 1988).
The specification discloses series of experiments conducted on a corneal wound healing mouse model, human organ culture and primary cultures of lung fibroblasts and dermal fibroblasts and treated either in culture or by direct application of NBL1 protein. The results demonstrate the benefits of the treatment, see pp. 25-30 and Fig. 1-8. There appears no further information related to treatment by any other route of administration of NBL1 protein, as broadly claimed, or by means of gene therapy. The instant specification does not provide neither enough guidance for such methods of treatment, nor working examples, which would show that the claimed method was successfully achieved, thus, requiring undue experimentation on part of one skilled in the art to discover how to practice the claimed invention.
The nature of the invention involving biological molecules and their effect on a physiological system is complex and unpredictable. As was found in Ex parte Hitzeman, 9 USPQ2d 1821 (BPAI 1987), a single embodiment may provide broad enablement in cases involving predictable factors such as mechanical or electrical elements, but more will be required in cases that involve unpredictable factors such as most chemical reactions and physiological activity. This 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). See also In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970); Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 927 F.2d 1200, 1212, 18 USPQ2d 1016, 1026 (Fed. Cir.), cert. denied, 502 U.S. 856 (1991).
The prior art recognizes NBL1 as a member of DAN family of proteins, antagonists of bone morphogenic proteins. Finding of direct association of NBL1 with fibrosis, pathology of adhesion formation or specifically with rheumatoid arthritis, congestive heart failure or Lyme disease has not been reported. It is also not recognized in the art that finding of experimental success of treating cells in culture by direct delivery of a protein can be immediately indicative of successful clinical administration of the protein in general, or by means of gene delivery of the encoding nucleic acid.
With respect to claim breadth, the standard under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, entails the determination of what the claims recite and what the claims mean as a whole. In addition, when analyzing the enablement scope of the claims, the teachings of the specification are to be taken into account because the claims are to be given their broadest reasonable interpretation that is consistent with the specification (see MPEP 2111 [R-1], which states that claims must be given their broadest reasonable interpretation, “During patent examination, the pending claims must be "given *>their< broadest reasonable interpretation consistent with the specification." In re Hyatt, 211 F.3d 1367, 1372, 54 USPQ2d 1664, 1667 (Fed. Cir. 2000). Applicant always has the opportunity to amend the claims during prosecution, and broad interpretation by the examiner reduces the possibility that the claim, once issued, will be interpreted more broadly than is justified. In re Prater, 415 F.2d 1393, 1404-05, 162 USPQ 541, 550- 51 (CCPA 1969).”
As such, the broadest reasonable interpretation of the claimed method is that it allows prevention and treatment of a large family of clinical conditions that include fibrosis, scarring and atypical adhesion formation as part of the pathology all by general administration of NBL1 protein, encoding nucleic acid or a cell recombinantly altered to express NBL1. Thus, the claims encompass an unreasonable number of diseases and disorders, which the skilled artisan would not know how to evaluate, prevent and treat. As opposed to the claims, what is disclosed about the claimed method is narrow: a set of experiments limited to direct application of NBL1 protein within a specific model of corneal wound healing and treatment of primary lung fibroblasts in vitro. There are no other obvious specific examples of other pathologies that are commensurate with the scope of the claimed methods, reference to the relevant disclosure of the prior art or any specific protocols or guidance as how to practice the full scope of instant claimed method. Moreover, no methods of prevention or treatment of any diseases or disorders by administration of NBL1 nucleic acids or genetically modified cells can be envisioned because the experiments provided within the specification do not directly support the inventive concept as claimed.
The standard of an enabling disclosure is not the ability to make and test if the invention worked but one of the ability to make and use with a reasonable expectation of success.
A patent is granted for a completed invention, not the general suggestion of an idea and how that idea might be developed into the claimed invention. If mere plausibility were the test for enablement under section 112, applicants could obtain patent rights to “inventions” consisting of little more than respectable guesses as to the likelihood of their success. In the decision of Genentec, Inc, v. Novo Nordisk, 42 USPQ 2d 100, (CAFC 1997), the court held that:
“[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable” and that “[t]ossing out the mere germ of an idea does not constitute enabling disclosure.” The court further stated that “when there is no disclosure of any specific starting material or of any of the conditions under which a process is to be carried out, undue experimentation is required; there is a failure to meet the enablement requirements that cannot be rectified by asserting that all the disclosure related to the process is within the skill of the art,” “[i]t is the specification, not the knowledge of one skilled in the art, that must supply the novel aspects of an invention in order to constitute adequate enablement.”
The instant specification is not enabling because one cannot follow the guidance presented therein and practice the claimed methods without first making a substantial inventive contribution to perfect the method and complete the invention.
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.
10. Claim(s) 47 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nolan et al., J Biol Chem, 2015, 290(8), 4759-71, reference 4 of IDS filed on 02/29/2024.
Claim 47 encompasses NPL1 protein. Nolan et al. teaches the structure of NPL1, thus fully anticipating the instant claimed subject matter.
Conclusion
11. No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OLGA N CHERNYSHEV whose telephone number is (571)272-0870. The examiner can normally be reached 9AM to 5:30PM, Monday to Friday.
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/OLGA N CHERNYSHEV/Primary Examiner, Art Unit 1675
July 31, 2026
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