DETAILED ACTION
Claims 1-20 are pending and being examined on the merits in this office 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
The filing receipt dated 4/22/2025 provides the following information:
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Drawings
The drawings are objected to for the following reasons.
Fig 2C is too small and pixelated to clearly distinguish the differences between shades of gray in the figure.
Fig 4A is too small and pixelated to decipher the text and images.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
Please note, the specification has not been checked to the extent necessary to determine the presence of all possible error. Applicant's cooperation is required in correcting any errors of which applicant may become aware in the specification. MPEP § 608.01.
Specification- Sequence
The specification is objected to for the following reason:
There is a discrepancy between SEQ ID NO:1 in the as-filed specification and the sequence filed in the Sequence Listing.
The Sequence listing indicates that the peptide is 64 amino acids in length.
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However, the sequence of SEQ ID NO:1 provided in the as-filed specification is 65 amino acids in length.
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Specifically, the 65 amino acid sequence set forth in the specification has the following sequence: SHLVKCAEKEKTFCVNGGECFMVKDLSNPSRYLCKCQPGFTGARCTENVPMKVQNQEKAEELYQK
The underlined, bold cysteine residue found in the sequence of the as-filed specification is missing in the peptide sequence of the Sequence listing.
The specification and Sequence Listing should be consistent with the sequence relating to SEQ ID NO:1.
Claim Objections
Claims 1, 5, 8, 9, 13, 17, and 19 are objected to because of the following informalities:
Claim 1 should be amended to recite: A method of treating a respiratory viral infection or decreasing [[the]] risk of developing a respiratory viral infection in a subject by administering a therapeutically effective amount of neuregulin to the subject in need thereof.
Claim 5 should be amended to depend from claim 4, instead of claim 1 because claim 5 further limits claim 4.
Claim 8 should be amended to recite “the subject is a human”.
Claim 9 should be amended to recite “A method of decreasing [[the]] risk that a subject will develop a post-viral airway disease … to the subject in need thereof:.
Claim 13 should be amended to depend from claim 12, instead of claim 9 because claim 13 further limits claim 12.
Claim 17 should be amended to recite “the subject is a human”.
Claim 19 should be amended to recite either “intra-nasally” or “intranasally”, hyphenated or as single word.
Appropriate correction is required.
Applicant is advised that should claim 15 be found allowable, claim 17 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Presently filed claims 15 and 17:
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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 9-20 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.
Claim 9 is drawn to a method of decreasing the risk a subject will develop post-viral airway disease by administering an effective amount of neuregulin to the subject.
Claim 9 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted steps are: claim 9 is missing 1) a correlation between the subject/patient population at risk for developing a post-viral airway disease and the type of virus/infection. In order for subject to be at risk for developing a post-viral airway disease, the subject must previously have had a viral infection that will place them at risk for developing post-viral disease. More specifically however, the subject must have previously had a respiratory virus infection (e.g., rsv or covid-19), as opposed to a general viral infection (e.g., chickenpox or HPV which affect skin), in order to render the subject in a patient population that places the subject at risk for developing a post-viral airway disease.
Claim 9 is further missing 2) a temporal relationship between the period of the respiratory viral infection and the point at which the subject would be at risk for developing post-viral airway disease. As presently written, there is no timeframe correlation between the initial viral infection, and timing of a risk for developing post-viral disease. A subject could have a respiratory viral infection but that is still be at risk for developing a post-viral airway disease many, many years later.
Because claims 10-20 depend from indefinite claim 9 and do not clarify the point of confusion, they must also be rejected under 35 U.S.C. 112(b).
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.
Claim(s) 1-3, 6-10, and 14-20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ford et al (U.S. 2014/0030251).
Ford et al teach compositions and methods for treating, preventing or ameliorating tissue damage caused by pathogenic infections (e.g., viruses) comprising administering neuregulin (e.g., abstract, para [0006], [0051]; claims 1, 7, 12, 16, 17, 21, and 23). Ford teaches that the respiratory disorders include chronic lung disease, asthma, and pneumonia (e.g., para [0017], claim 12). Ford teaches the terms “treat,” “treating” or “treatment” as used herein, refers to a method of alleviating or abrogating a disorder and/or its attendant symptoms. The terms “prevent”, “preventing” or “prevention,” as used herein, refer to a method of barring a subject from acquiring a disorder and/or its attendant symptoms (para [0041]). A “therapeutically effective amount” of a neuregulin refers to an amount effective in the prevention or treatment of a disorder for the treatment of which the active agent is effective (para [0049]). The reference teaches neuregulin is administered in a dosage range from about 0.01 mg/kg body weight/day to about 1000 mg/kg body weight/day (e.g., paras [0006], [0008], claim 1). Accordingly, the limitations of instant claims 1 and 9 are satisfied. With further regard to claim 9, the terms “prevent,” “preventing” or “prevention” refer to a method of reducing the risk of acquiring a disorder and/or its attendant symptoms (para [0041]). Accordingly, Ford is construed as satisfying the limitations of instant claim 9.
Regarding claims 2 and 10, Ford teach that neuregulin includes neuregulin-1 (e.g., para [0036]). Regarding claim 3, Ford teaches that the respiratory disorders include chronic lung disease, asthma, and pneumonia (e.g., para [0017], claim 12).
Regarding claims 6 and 18, neuregulin can be administered to pulmonary tissue, e.g., bronchoalveolar tissue may be contacted by inhalation of a liquid or powder aspirate [reads on pulmonary administration] (e.g., paras [0129], [0127], [0139]). Regarding claims 7 and 20, Ford teaches for administration by inhalation, the compounds are delivered in the form of an aerosol spray from pressured container or dispenser which contains a suitable propellant, e.g., a gas such as carbon dioxide or a nebulizer (e.g., para [0143]). Regarding claim 8, 15 and 17, the subject is human (e.g., para [0148]). Regarding claim 14, Ford discloses that “pathogenic infection” refers to the invasion of body tissues by disease-causing microorganisms, their multiplication and the reaction of body tissues to these microorganisms and the toxins that they produce. “Pathogenic infection” includes infections by viruses (para [0051]). The reference further discloses treating (alleviating or abrogating a disorder and/or its attendant symptoms) and/or preventing (barring a subject from acquiring a disorder and/or its attendant symptoms; reducing the risk of acquiring a disorder and/or its attendant symptoms) (para [0041). Regarding claim 16, Ford teaches that the inflammatory disorder or pathogenic infection is an inflammatory disease or infection of the respiratory system selected from the group consisting of chronic lung disease, asthma, and pneumonia (e.g. paras [0017], [0118], claim 12). Regarding claim 19, neuregulin administration can be by nasal spray [reads on intra-nasal administration].
Pursuant to MPEP 2121(I), when the reference relied on expressly anticipates or makes obvious all the elements of the claimed invention, the reference is presumed to be operable. Once such a reference is found, the burden is on applicant to rebut the presumption of operability. In re Sasse, 629 F.2d 675, 207 USPQ 107 (CCPA 1980). Moreover, MPEP 2121(III) states that a prior art reference provides an enabling disclosure and thus anticipates a claimed invention if the reference describes the claimed invention in sufficient detail to enable a person of ordinary skill in the art to carry out the claimed invention; "proof of efficacy is not required for a prior art reference to be enabling for purposes of anticipation." Impax Labs. Inc. v. Aventis Pharm. Inc., 468 F.3d 1366, 1383, 81 USPQ2d 1001, 1013 (Fed. Cir. 2006). MPEP 716.07 states that since in a patent it is presumed that a process if used by one skilled in the art will produce the product or result described therein, such presumption is not overcome by a mere showing that it is possible to operate within the disclosure without obtaining the alleged product. In re Weber, 405 F.2d 1403, 160 USPQ 549 (CCPA 1969).
Claim Rejections - 35 USC § 103
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) 1-20 is/are rejected under 35 U.S.C. 103 as being unpatentable Ford et al (U.S. 2014/0030251), and further in view of Hussain et al (J. Immunol 207:2589-2527 (epublished October 8, 2021)), as evidenced by (Hussain et al J. Immunol 207:2589-2527 (2 pages, indicating reference was epublished October 8, 2021- accessed 8/7/2026 at PubMed URL pubmed.ncbi.nlm.nih.gov/34625522/)).
Ford et al teach compositions and methods for treating, preventing or ameliorating tissue damage caused by pathogenic infections (e.g., viruses) comprising administering neuregulin (e.g., abstract, para [0006], [0051]; claims 1, 7, 12, 16, 17, 21, and 23). Ford teaches that the respiratory disorders include chronic lung disease, asthma, and pneumonia (e.g., para [0017], claim 12). The reference further discloses treating (alleviating or abrogating a disorder and/or its attendant symptoms) and/or preventing (barring a subject from acquiring a disorder and/or its attendant symptoms; reducing the risk of acquiring a disorder and/or its attendant symptoms) (para [0041). A “therapeutically effective amount” of a neuregulin refers to an amount effective in the prevention or treatment of a disorder for the treatment of which the active agent is effective (para [0049]). The reference teaches neuregulin is administered in a dosage range from about 0.01 mg/kg body weight/day to about 1000 mg/kg body weight/day (e.g., paras [0006], [0008], claim 1). Ford teaches that neuregulin includes neuregulin-1 (e.g., para [0036]). Respiratory disorders include chronic lung disease, asthma, and pneumonia (e.g., para [0017], claim 12).
Ford does not explicitly teach that the respiratory infection is a recited virus infection.
Hussain et al teach that respiratory syncytial virus (RSV) infection in infancy is associated with increased risk of asthma, except in those with allergic disease at the time of infection (abstract). Respiratory viral infections may drive development of atopic disease (as well as exacerbating existing disease). Rhinovirus and RSV are the two main respiratory viruses associated with increasing risk of developing asthma (pp. 2-3 of attached reference).
It would have been obvious to one of ordinary skill in the art to administer a therapeutically effective amount of neuregulin to a subject with a rhinovirus or a respiratory syncytial virus (RSV) infection in order to treat and/or decrease the risk of developing a respiratory viral infection. The skilled artisan would have known from Ford that neuregulin could be administered to a subject with a respiratory viral infection to reduce the epithelial tissue damage of the respiratory tract/lungs caused by the infection. Hussain taught that Rhinovirus and RSV cause respiratory viral infections occur in humans. The skilled artisan would have had a reasonable expectation of success in treating a subject with a respiratory viral infection with neuregulin because this is the specific patient population that Ford sought to treat with neuregulin.
It is noted that the as-filed specification states at para [0016]:
As used herein, the terms "treatment," "treating," and the like, refer to obtaining a desired pharmacologic or physiologic effect. The effect may be therapeutic in terms of a partial or complete cure for a disease or an adverse effect attributable to the disease. "Treatment," as used herein, covers any treatment of a disease in a mammal, particularly in a human, and can include inhibiting the disease or condition, i.e., arresting its development; and relieving the disease, i.e., causing regression of the disease.
Thus, treating tissue damage caused by the respiratory viral infection with neuregulin satisfies the instant claims. Accordingly, claims 4 and 5 are rendered obvious.
With regard to claims 12 and 13, it would have been obvious to one of ordinary skill in the art to administer a therapeutically effective amount of neuregulin to a subject with a rhinovirus or a respiratory syncytial virus (RSV) infection in order to decrease the risk of developing a post-viral airway disease. The skilled artisan would have known from Ford that neuregulin could be administered to a subject with a respiratory viral infection to reduce the epithelial tissue damage of the respiratory tract/lungs caused by the virus infection. Ford further taught that administering neuregulin reduced the risk of acquiring a disorder and/or its attendant symptoms. Hussain taught that Rhinovirus and RSV were associated with increased risk of developing post-viral asthma. The skilled artisan further would have known from Ford that neuregulin could be used to treat asthma and pneumonia. The skilled artisan would have had a reasonable expectation of success in treating a subject with a respiratory viral infection with neuregulin to because this is the specific patient population (viral respiratory infection and those with/as risk for developing asthma] that Ford sought to treat with neuregulin.
Accordingly, claims 12 and 13 are rendered obvious.
Regarding claim 11, the subject has RSV (Hussain at 2-3; see also mouse model of SeV virus which is a mouse model of RSV at pp. 4, 8-9, 23-25). Further regarding claim 14, subjects with a RSV infection are an increased risk of asthma and allergic disease (Hussain at pp. 2-3) Further regarding claim 16, the postviral airway disease is asthma, as taught by Hussain.
Accordingly, the instant claims are rendered obvious in view the teachings of the cited references.
Relevant Art Not Relied Upon
Sliwkowski et al (U.S. 20030199429) teach a method of regenerating and/or repairing epithelial cell injury by stimulating growth and proliferation of epithelial cells, in particular ductal and ciliated epithelial cells. The epithelial cells may be injured by many types of insults, for example, injury due to surgical incision or resection, chemical or smoke inhalation or aspiration, chemical or biochemical ulceration, cell damage due to viral or bacterial infection, etc. Treatment of the lung cells regenerates the barrier layer of lung epithelial cells, improves oxygenation and speeds the development of a barrier to infection (e.g., paras [0027]-[0035], claims 1-2). Activating ligand include heregulin (HRG) polypeptide and HRG variant (eg, paras [0048]-[0052], claims 1-2). HRG can be used to induce epithelial cell growth, for example lung epithelial cell growth, proliferation and differentiation, and to increase the production of surfactant protein A by lung cells. These effects allow treatment of disease states associated with tissue damage, for example, chronic obstructive pulmonary disease (COPD) including subtypes thereof such as chronic bronchitis, emphysema, asthma, etc., neonatal pulmonary diseases including neonatal respiratory distress syndrome, meconium aspiration syndrome, chronic lung disease of the neonate, congenital diaphragmatic hernia, etc., acute lung injuries including smoke or chemical inhalation, pneumonitis due to aspiration, radiation, etc., near drowning, cystic fibrosis and other epithelial cell trauma diseases, including injuries associated with surgical wounds and resections, ulcers, lesions, and tissue tears (paras [0295]-[0297]). Sliwkowski et al further teach a method of treating respiratory distress syndrome in patients, primarily human patients, in need of such treatment; as well as a method of inducing lung epithelial cell growth and development (e.g., para [0028], [0034], claims 14-19).
As indicated in the as-filed specification at para [0024], “NRG-1 isoforms include type I (Heregulin), type II (Glial Growth Factor-2), type III (Sensory and motor neuron-derived factor), type IV, type V, and type VI NRG-1”.
Shalek et al (WO 2022/178312- earliest effective filing date 2/18/2021) teach methods of stratifying and treating coronavirus infections (abstract). The claims recite a method of treating a barrier tissue infection (e.g., respiratory barrier tissue infection) in a subject in need thereof comprising detecting one or more indicators of infection (e.g., respiratory barrier tissue infection) from a sample obtained from the subject, wherein the sample comprises one or more of epithelial, immune, stromal, and neuronal cells; comparing the indicators to control/healthy samples or disease reference values to determine whether the subject will progress to a risk group selected from (i) mild/moderate disease; or (ii) severe disease; and administering one or more treatments if one or more indicators are present. The infection is a coronavirus viral infection (claims 4-5). Treatments include a) one or more antiviral; b) blood-derived immune-based therapy; c) one or more corticosteroid; d) one or more interferon; e) one or more interferon Type I agonists; f) one or more interleukin-1 inhibitors; g) one or more kinase inhibitors; h) one or TLR agonists; i) a glucocorticoid; and j) interleukin-6 inhibitor (claim 31). The antiviral is selected from the group consisting of paxlovid, molnupiravir and remdesivir (claim 35). The reference does not teach or suggest neuregulin.
Zhou (U.S. 2011/0135595) teach a method for preventing, treating or delaying myocardial infarction, viral myocarditis, dilated (congestive) cardiomyopathy (DCM) or cardiac toxicity in a mammal, which method comprises administering to a mammal, to which such prevention, treatment or delay is needed or desirable, an effective amount of a neuregulin protein, or a functional fragment thereof (claim 95). The viral myocarditis is caused by or associated with infection of a virus selected from the group consisting of Coxsackie Group A virus, Coxsackie Group B virus, ECHO virus and polio virus (claim 24).
Conclusion
No claims are allowed.
Claims 1-20 are pending and are rejected.
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/KRISTINA M HELLMAN/Examiner, Art Unit 1654
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