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 .
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.
Claim(s) 1, 3, 4, 6, 7, 9, 12, 13 and 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Oh et al. (US10,370,426) in view of Bloodworth et al. (Letter to the Editor, Volume 142, Issue 2, p, 683-687).
Claim 1 is drawn to a method of “preventing or treating sequalae following a respiratory infection,” which is defined in the specification as “abnormal symptoms that appear in patients with respiratory infectious diseases independently after treatment of respiratory infectious diseases.” Because the claims are drawn to prevention, they are interpreted to mean that the subject “in need thereof” must be or have been infected with the claimed virus, but does not yet need to manifest the claimed sequelae, as the patient class includes any subject experiencing or recovering from the recited respiratory infection.
Oh teaches the same peptide as instantly claimed SEQ ID NO 22:
PNG
media_image1.png
234
354
media_image1.png
Greyscale
(p. 24). This aligns 100% with instantly claimed SEQ ID NO: 22 because Xaa is AIB in both sequences:
PNG
media_image2.png
174
652
media_image2.png
Greyscale
This reference teaches that the peptide is a Triple Glucagon/GLP-1/GIP Receptor Agonist and that pharmaceutical formulations with acceptable excipients are used to treat various metabolic conditions and to perform the functions of promoting the secretion of insulin in the pancreas in a blood glucose-dependent manner to lower the blood glucose levels, thereby increasing the activation of GLP-1 and reducing inflammation (Col. 1, lines 45-60; Col. 18, lines 50-60, Col. 20 entire column).
The difference between the prior art and the instant claims is that the prior art does not teach that the peptides are used for preventing or treating sequelae following a respiratory infectious disease.
Bloodworth teaches that Glucagon-like peptide 1 receptor (GLP-1R) agonists, which potentiate insulin and suppress glucagon secretion, are primarily for their endocrine properties, but evidence suggests that GLP-1R signaling also has anti-inflammatory effects, which were observed in respiratory syncytial virus (RSV) that are in part caused by IL-13 production (p. 683, Col. 2, para. 1). Bloodworth hypothesizes that GLP-1R signaling inhibits IL-13–mediated immunopathology of RSV 12/12-6, a strain of RSV that was isolated from a hospitalized infant with severe lower respiratory tract infection and bronchiolitis (p. 683, Col. 2, para. 1). Based on this hypothesis, Bloodworth teaches that mice were infected with RSV 12/12-6, which induced significant lung IL-13 and airway mucus increases, mimicking what is seen in patients with severe RSV infection (see Fig E1; P. 684, Col. 2, para 2). Bloodworth teaches that mice were administered either a GLP-1R agonist (liraglutide) or vehicle (0.1% BSA in PBS) twice daily beginning 2 days before RSV infection and continued until all end points were reached (p. 683, Col. 2, para. 2, Fig E2). This reference found that GLP-1R agonist treatment significantly decreased lung IL-13 protein expression compared with vehicle treatment in RSV-infected mice (p. 683, Col. 2, para. 2, Fig 1, A). Additionally, administration of the GLP-1R agonist beginning 2 days after RSV infection significantly decreased lung IL-13 levels, and there was a trend toward decreased airway mucus, which demonstrates that GLP-1R signaling attenuates IL-13-mediated immunoipathology (Spanning p. 685-686). In a further experiment, this reference teaches that mice infected a second time that had been treated with the GLP-1R agonist during primary infection did not exhibit altered lung IFN- ỿ expression or RSV F-protein–specific antibody responses compared with vehicle-treated mice during secondary RSV infection, showing that that GLP-1R agonist treatment does not exacerbate disease or impede antiviral responses upon secondary infection (see Fig E9, B-E). Finally, Bloodworth teaches that there were significant decreases in methacholine induced airway responsiveness and mucus severity scores in RSV-infected GLP-1R agonist–treated mice compared with RSV-infected vehicle-treated mice (p. 684, Col. 2, Fig 1, F-H).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have taken the GLP-1R agonist of Oh and used it to prevent and/or treat sequelae following RSV infection because Bloodworth effectively shows that GLP-1R agonists reduce lung mucus severity scores and attenuate IL-13-mediated immunoipathology. One would be motivated to do so because Oh and Bloodworth both teach that peptide GLP-1R agonists mimic GLP-1 and activate GLP-1 receptors in the pancreas to boost glucose-dependent insulin release and lower blood glucose levels and inflammation. As such, there is a reasonable expectation of success that the peptides of Oh can effectively mitigate the cytokine response in respiratory infections to prevent and/or treat various sequelae following RSV infection.
Claims 1 and 16 are met because Oh teaches the same SEQ ID NO: 22 as the instantly claimed SEQ ID NO: 22 and Bloodworth provides motivation to administer the GLP-1R agonist of Oh to subjects that are or have been infected with RSV. Claim 3 is met because RSV is respiratory syncytial virus. Claim 4 is met because Bloodworth teaches treating RSV. Claim 9 is met because both references teach that the GLP-1R agonists decrease inflammation. Claims 6-7 are met because Bloodworth teaches strain RSV 12/12-6, which is a variant in the broad definition of the specification. The specification states that respiratory virus variants “may include variant viruses in which mutations occur in the genomic sequence or trait, but are not limited thereto,” and that “variant viruses of the present invention may refer to viruses that may cause the same sequelae even having mutations, as compared with the respiratory virus.” This does not limit the variant to any particular type of differentiation or mutation required, and allows for the specific strain isolated for the experiment to be considered to mimic severe respiratory infection from RSV, as the sequalae of respiratory track inflammation and increased cytokine expression would be expected to be similar, but differ in severity across RSV strains. Claim 10 is met because the claims are drawn to prevention, and there is clear motivation to administer GLP-1R agonists, because both references teach that they work via the same mechanism of increasing insulin in the pancreas and treating inflammation to any subject that has had RSV, regardless of whether the sequelae of tissue damage. Claims 12-13 are met because IL-33 was reduced by GLP-1 R agonist administration.
Claim(s) 1-4, 6-7, 9, 10, 12-14 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Oh et al. (US10,370,426) in view of Bloodworth et al. (Letter to the Editor, Volume 142, Issue 2p 683-687), as applied to claims 1, 3, 4, 6-7, 9, 10, 12-13 and 16 above, and in further view of Hwang et al. (US2017/0298117).
The teachings of Oh and Bloodworth have been described supra.
The difference between the prior art and the instant claims is that the prior art does not teach that the GLP-1R agonist is conjugated to PEG and the immunoglobulin Fc region.
Hwang teaches that GLP-1/glucagon receptor agonists may be in long-acting conjugate form, wherein a biocompatible material or a carrier is linked directly to the GLP-1/glucagon receptor dual agonist by a covalent bond to improve the half-life or bioavailability [0020]. This reference teaches that one example of the long-acting GLP-1/glucagon receptor dual agonist is a composition in which the immunoglobulin Fc region is linked to the 30th amino acid of the GLP-1/glucagon receptor agonist by the non-peptide polymer linker, preferably PEG, [0020]. This reference further teaches that long-acting GLP-1/glucagon receptor agonists inhibit inflammation by reducing the expression or activity of tumor necrosis factor-α (TNF-α), which is a pro-inflammatory marker [0017].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to have taken the agonist of Oh and used the long-acting conjugate of Hwang in the method of treating RSV, as taught by Bloodworth because they have longer bioavailability and half-life. One would be motivated to do so because Hwang teaches that such conjugates have improved long-acting characteristics compared to non-conjugated GLP-1R agonists and work by the same mechanism. As such, there is a reasonable expectation of success that the GLP-1R agonist of Oh can be used to treat RSV in the conjugate of Hwang.
This meets the limitation of claim 2 by teach PEG and Fc conjugation to the GLP-1R agonist. Additionally, claim 14 is met because Hwang teaches that such agonists reduce TNF-α cytokines to combat inflammation.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-4, 6-7, 9, 10, 12-14 and 16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2 and 7 of copending Application No. 18/565,628 in view of Bloodworth.
Claim 1 teaches a method for treating lung disease with the same SEQ ID Nos: 1-102.
The difference between ‘628 and the instant claims is that ‘638 does not teach a method of treating sequalae following the lung disease, or respiratory infection.
However, as discussed above, Bloodworth teaches Bloodworth teaches that Glucagon-like peptide 1 receptor (GLP-1R) agonists, which potentiate insulin and suppress glucagon secretion, are a well-accepted are currently used primarily for their endocrine properties, but recent evidence suggests that GLP-1R signaling also has anti-inflammatory effects, which were observed in respiratory syncytial virus (RSV), which is in part caused by IL-13 production (p. 683, Col. 2, para. 1). Bloodworth hypothesized that GLP-1R signaling inhibits IL-13–mediated immunopathology of RSV 12/12-6, a strain of RSV that was isolated from a hospitalized infant with severe lower respiratory tract infection and bronchiolitis (p. 683, Col. 2, para. 1). Based on this hypothesis, this study teaches that mice were infected with RSV 12/12-6, which induced significant lung IL-13 and airway mucus, mimicking what is seen in patients with severe infection (see Fig E1; P. 684, Col. 2, para 2). Bloodworth teaches that they administered the GLP-1R agonist or vehicle (0.1% BSA in PBS) twice daily beginning 2 days before RSV infection and continued until all end points were reached (p. 683, Col. 2, para. 2, Fig E2). This experiment found that GLP-1R agonist treatment significantly decreased lung IL-13 protein expression compared with vehicle treatment in RSV-infected mice (p. 683, Col. 2, para. 2, Fig 1, A). Additionally, administration of the GLP-1R agonist beginning 2 days after RSV infection also significantly decreased lung IL-13 levels, and there was a trend toward decreased airway mucus, which demonstrates that GLP-1R signaling attenuates IL-13-mediated immunoipathology (Spanning p. 685-686). In a further experiment, this reference teaches that mice infected a second time that were treated with GLP-1R agonist during primary infection did not exhibit altered lung IFN- ỿ expression or RSV F-protein–specific antibody responses compared with vehicle-treated mice during secondary RSV infection, showing that that GLP-1R agonist treatment does not exacerbate disease or impede antiviral responses upon secondary infection (see Fig E9, B-E). Finally, Bloodworth teaches that there were significant decreases in methacholine induced airway responsiveness and mucus severity scores in RSV-infected GLP-1R agonist–treated mice compared with RSV-infected vehicle-treated mice (p. 684, Col. 2, Fig 1, F-H).
It would have been obvious to one of ordinary skill in the art at the time of the invention to have taken the GLP-1R agonist of ‘628 and used it to treat RSV because Bloodworth effectively shows that GLP-1R agonists are reduces lung mucus severity score by attenuating IL-13-mediated immunoipathology. One would be motivated to do so because ‘3 and Bloodworth both teach that the GLP-1R agonists mimics the GLP-1 hormone and activate GLP-1 receptors in the pancreas to boost glucose-dependent insulin release and lower blood glucose levels. As such, there is a reasonable expectation of success that the peptides of ‘628 can effectively mitigate the cytokine response in respiratory infections to prevent and treat sequelae following infection.
Claims 1 and 16 are met because ‘683 teaches the same SEQ ID NO: 22 as the instantly claimed SEQ ID NO: 22 in a method of treating lung disease, and Bloodworth provides motivation to administer the GLP-1R agonist of ‘628 to subjects that are or have been infected with RSV. Claim 3 is met because RSV is respiratory syncytial virus. Claim 4 is met because Bloodworth teaches treating RSV. Claim 9 is met because both references teach that the GLP-1R agonists decrease inflammation. Claims 6-7 are met because Bloodworth teaches strain RSV 12/12-6, which is a variant, as the specification states that variant “may include variant viruses in which mutations occur in the genomic sequence or trait, but are not limited thereto. The variant viruses of the present invention may refer to viruses that may cause the same sequelae even having mutations, as compared with the respiratory virus.” This does not limit the variant to any particular type of differentiation or mutation required, and allows for the specific strain isolated for the experiment to be considered to mimic severe respiratory infection from RSV, as the sequalae of respiratory track inflammation and increased cytokine expression would be expected to be similar, but differ in severity across RSV strains. Claim 10 is met because the claims are drawn to prevention, and there is clear motivation to administered GLP-1R agonists, which work via the same mechanism of increasing insulin in the pancreas and treating inflammation to any subject that has had RSV, regardless of whether the sequelae of tissue damage. Claims 12-13 are met because IL-33 was reduced by GLP-1 R agonist administration.
This is a provisional nonstatutory double patenting rejection.
Claims 1-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of copending Application No. 17/792,228.
The claims of ‘228 teach the following:
1. A method for treating lung disease, comprising administering a pharmaceutical composition for the prevention or treatment of lung disease, comprising: a pharmaceutically acceptable excipient; and a peptide comprising an amino acid sequence of any one of SEQ ID NOS: 1 to 102 in a pharmaceutically effective amount to a subject in need thereof.
2. The method of claim 1, wherein the peptide is in a form of a long-acting conjugate, and the long-acting conjugate is represented by Formula 1 below:
X-L-F [Formula 1] wherein in Formula 1 above, X is a peptide of an amino acid sequence of any one of SEQ ID NOS: 1 to 102; L is a linker comprising an ethylene glycol repeat unit; F is an immunoglobulin Fc region; and “-” represents a covalent bond between X and L and between L and F.
3. The method of claim 1, wherein the C-terminus of the peptide is amidated.
4. The method of claim 1, wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 21, 22, 42, 43, 50, 64, 66, 67, 70, 71, 76, 77, 96, 97, and 100.
5. The method of claim 4, wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 21, 22, 42, 43, 50, 77, and 96.
6. The method of claim 1, wherein amino acid residues at positions 16 and 20 from the N-terminus of the amino acid sequence form a ring with each other in the peptide.
7. The method of claim 2, wherein formula weight of the ethylene glycol repeat unit portion in the L is in the range of 1 kDa to 100 kDa.
8. The method of claim 2, wherein the F is an IgG Fc region.
9. The method of claim 1, wherein the lung disease is interstitial lung disease (ILD), progressive fibrosing interstitial lung disease (PF-ILD), idiopathic interstitial pneumonias (IIP), non-specific interstitial pneumonia (NSIP), pulmonary fibrosis, fibrosing interstitial lung diseases (FILD), idiopathic pulmonary fibrosis (IPF), alveolitis, pneumonia, emphysema, bronchitis, chronic obstructive pulmonary disease, combined pulmonary fibrosis and emphysema (CPFE), asthma, respiratory infectious disease, or combinations thereof.
10. The method of claim 9, wherein the respiratory infectious disease is an infectious disease caused by respiratory viruses, bacteria, mycoplasma, or fungi.
11. The method of claim 10, wherein the respiratory virus is any one selected from the group consisting of adenovirus, vaccinia virus, herpes simplex virus, parainfluenza virus, rhinovirus, varicella zoster virus, measles virus, respiratory syncytial virus, Dengue virus, HIV (human immunodeficiency virus), influenza virus, coronavirus, severe acute respiratory syndrome associated virus (SARS-associated virus), and middle east respiratory syndrome coronavirus (MERS-CoV).
12. The method of claim 11, wherein the coronavirus is SARS-CoV-2.
Claims 1-7, 9 and 16 are met because claims 1-2 of ‘228 teach treating lung diseases with the same peptides (SEQ ID Nos: 1-102, including Sars-Cov-2, which would be administering the same composition to the same patient class that have had the virus and preventing potential sequalae associated with the conditions. Claim 11 is met because claim 11 of ‘228 teaches treating coronavirus, and claim 9 of ‘228 teaches treating pulmonary fibrosis as a sequalae of infection. Furthermore, the instant claims are drawn to preventative methods, and the same peptides are being administered to the same patient class of those that had a respiratory virus, including Sar-Cov-2.
As to instant claims 10 and 12-15, the same respiratory diseases are taught to be treated by the same exact SEQ ID NO: 22, rendering the ne reaction and effect of the peptide administration inherent to the method taught by the claims of ‘228, as the same mechanisms of reducing cytokines would be expected to occur upon administration, absent evidence to the contrary.
As such, the instant claims are rendered obvious by the claims of ‘228. As to claim 8, the same sequelae for Sars-cov-2 would be expected to be effective for the variants of Sars-Cov-2 variants, as they have the similar underlying pathologies, as evidenced by Ahmed et al. (Int J Mol Sci. 2025 Jan 31;26(3):1263).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANETTE M LIEB whose telephone number is (571)270-3490. The examiner can normally be reached M-F 10-7.
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, Lianko Garyu can be reached on 571-270-7367. 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.
/JEANETTE M LIEB/Primary Examiner, Art Unit 1654
Prosecution Insights