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 112(B)
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.
The term “decline in quality of life” in claim 5 is a relative term which renders the claim indefinite. The term “decline” and “quality” are 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. There is no measure by which this symptom can be medically established, as quality of life is subjective and dependent on many factors that are not determined by a viral infection.
Claim Rejections 35 USC 112(A)
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 1, 2, 4, 7, 11, 14, 17, 28, 31, 38-40, 42 and 53-55 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP § 2137 states that "the written description requirement for a genus must be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C), above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
For written description, the analysis (a) considers actual reduction to practice, (b) disclosure of drawing or structural chemical formulas, (c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties, functional characteristics when coupled with known or disclosed and (d) representative number of examples.
(a) actual reduction to practice/(b) disclosure of drawing or structural chemical formulas:
The present application has provided SEQ ID NOs: 1-211 of Cav-1 protein, which is a significant number of variations, but does not account for “one or more amino acid substitutions, insertions, deletions, or modifications.”
There is no upper limit to the number of residues that can be altered by this limitation, which allows for any of the amino acids in any sequence to be substituted, functionally incompatible sequences to be inserted, and all but a four residue fragment to be deleted. There are no examples in the specification showing any of the residues of SEQ ID NO 3: FTTFTVT can be deleted, substituted or have insertions.
(c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties
The sufficient relevant characteristics for the cav-1 peptide are the residues of minimum fragment of the claimed sequences, SEQ ID NO 3: FTTFTVT. This appears to be the common structural core that links the 211 sequences to the function of Cav-1 in treating post-acute COVID-19 disease. There are insufficient characteristics in the remaining portion of the peptide to establish that any would function as claimed, if the core region were altered.
(d) Representative number of examples
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004)("[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.").
Applicants have provide 211 peptide sequences, but there are no examples without SEQ ID NO 3: FTTFTVT that can establish the claimed function for the broad genus of peptides. Given this lack of description in the specification, the application fails to describe the claimed invention in such a full, clear, and concise and exact terms that a skilled artisan would recognize that applicants were in possession of the genus of claimed invention.
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, 2, 5, 7, 11, 14, 17, 19-21, 25, 28, 31, 38-40, 42 and 53-55 are rejected under 35 U.S.C. 103 as being unpatentable over Christensen (WO2020/055812) in view of Glassberg Csete (US2020/0384034).
Claim Interpretation
Claim 1 is drawn to a method of treating or preventing post-acute coronavirus disease with a modified caveolin-1 (“Cav-1”) peptide. As to the specific term “post-acute coronavirus disease,” (i.e., post-acute coronavirus syndrome “PACS”), the specification provide many embodiments, but does not provide a limiting definition of the disease. The art defines it as this is characterized by persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms (Nalbandian et al. Post-acute COVID-19 syndrome. Nat Med. 2021 April ; 27(4): 601–615). Because the symptoms of post-acute COVID-19 are an extremely broad variety of conditions and diseases, that include for example, anxiety, joint pain, chest pain, hypertension, hair loss, and many others, the only true marker of the patient class for the currently claimed method is that the subject currently has or has previously had a COVID-19 infection. Because the disease is defined in the art as starting 4 weeks after infection, the patient class that is considered to fall within claim 1 are those who have an active COVID-19 infection or those that have had COVID-19 within the previous four weeks, regardless of whether or not the subject has had symptoms.
Christensen teaches methods of using the modified Cav-1 peptides for the treatment of lung infections or acute or chronic lung injury, particularly lung fibrosis (Abstract). This reference teaches that during lung injury, p53 expression increases, inducing plasminogen activator inhibitor- 1 (PAI-l) while inhibiting expression of urokinase-type plasminogen activator (uPA) and its receptor (uPAR), resulting in apoptosis of lung epithelial cells (LECs) [0003]. Christensen teaches that this mechanism of injury involves cell surface signaling interactions between uPA, uPAR, Cav-1 and b1-integrin, such that modulating these interactions can be used for inhibiting apoptosis of damaged lung epithelial cells, treating acute lung injury and treating/preventing the consequent pulmonary fibrosis [0003]. This reference teaches this method of treatment with Cav-1 peptides comprising the amino acid sequence ASFTTFTVT (SEQ ID NO: 3), wherein the peptide comprises at least one N- or C-terminal addition to the N-terminus and/or the C-terminus [0004]. Christensen also teaches that the peptide comprises at least one non-standard amino acid, which may be ornithine, as well as both D- and L- amino acids [0007; 0054]. Specifically, Christensen teaches the amino acid sequences KASFTTFTVTKGS (SEQ ID NO: 4),aaEGKASFTTFTVTKGSaa (SEQ ID NO: 6). OASFTTFTVTOS (SEQ ID NO: 9), aaEGKASFTTFTVTKGSaa-NH2 (SEQ ID NO: 7), Ac-aaEGKASFTTFTVTKGSaa- NH2 (SEQ ID NO: 8) or OASFTTFTVTOS-NH2 (SEQ ID NO: 10) [0007].
Christensen further teaches N- and C- terminal modifications (i.e., terminal caps), where the N-terminal modification is acylation and the C-terminal modification is amidation [0009]. This reference teaches that the peptides may also comprise a cell penetrating peptide (‘CPP’ or ‘internalization sequence’) added to the peptide sequence [0094]. Christensen teaches that “cell penetrating peptide” and “membrane translocation domain” are also used interchangeably and refer to segments of polypeptide sequence that allow a polypeptide to cross the cell membrane and that examples of CPP segments include, but are not limited to, segments derived from HIV Tat (e.g., GRKKRRQRRRPPQ (SEQ ID NO: 21)), Penetratin (RQIKIWF QNRRMKWKK (SEQ ID NO: 22)), melittin (GIGAVLKVLTTGLPALISWIKRKRQQ (SEQ ID NO: 23)), Tl (TKIESLKEHG (SEQ ID NO: 24)), T2 (TQIENLKEKG (SEQ ID NO: 25)), 26 (AALEALAEALEALAEALEALAEAAAA (SEQ ID NO: 26)) and INF7 (GLFEAIEGFIENGWEGMIEGWY GCG (SEQ ID NO: 27)) [0094]. This reference further teaches that the composition may also comprise chloroquine in a pharmaceutically acceptable carrier [0097-0098]. Finally, Christensen teaches that the composition may be administered to the subject via inhalation or nebulization [0013, 0100].
The difference between the prior art and the instant claims is that the prior art does not teach that subject has or has previously had COVID-19.
Glassberg Csete teaches that COVID-19 can present as an asymptomatic carrier state, acute respiratory disease, and pneumonia. Adults represent the population with the highest infection rate; however, neonates, children, and elderly patients can also be infected by SARS-CoV-2. In addition, nosocomial infection of hospitalized patients and healthcare workers, and viral transmission from asymptomatic carriers are possible [0044]. This reference teaches that a method of using Cav-1 as both a diagnostic and therapeutic candidate for diagnosing and optimizing long term health and therapeutic benefit in a susceptible subject with an acute lung injury progressive to pulmonary fibrosis caused by viral infection, including SARS-CoV, CoVID-19, MERS and other viral respiratory diseases [0287]. This reference further teaches that the severe infection with a respiratory virus, including COVID-19, comprises an acute lung injury, acute respiratory distress syndrome, or both [0612]. This reference teaches that antifibrotic Cav-1 protein expression is reduced in mouse model of pulmonary fibrosis [0370]. Christensen teaches that the methods include administering a therapeutic amount of a pharmaceutical composition comprising extracellular vesicles (EVs) comprising one or more miRNAs and a pharmaceutically acceptable carrier [Abstract]. This reference teaches that the ASC exosomes (therapeutic) treated punches also showed an increase in anti-fibrotic Cav-1 (FIG. 23D) compared to the control [0370-0372; FIG. 23C].
It would have been obvious to one of ordinary skill in the art at the filing date of the invention to have taken the method of Christensen and administered the Cav-1 peptides to a subject that has or has had COVID-19 because Glassberg Csete teaches that the same lungs conditions treatable with Cav-1 are also effects of COVID-19 infections. One would be motivated to administer the same Cav-1 proteins of Christensen to the same patient class of those having or susceptible to pulmonary fibrosis or other lung injuries, but who also currently have or have had COVID-19 because Glassberg Csete teaches that COVID-19 infections cause lung injuries and fibrosis. As such, there is a reasonable expectation of success that the method of treating or inhibiting lung injuries and fibrosis with the Cav-1 peptides of Christensen will be effective in the patient class of those susceptible to post infection fibrosis and lung injuries.
Claims 1-2 are met because Christensen and Glassberg Csete provide motivation to administer Cav-1 peptides to subjects who have had COVID-19, and who are either currently infected or postinfection. As such, administering Cav-1 during or after COVID-19 infection to treat and prevent lung fibrosis and injuries, as well as the plethora of conditions associated with PACS, is rendered obvious. Claim 5 is met because both references teach treating pulmonary fibrosis and lung injuries. Claim 7 is met because Christensen teaches D- and L- amino acids. Claim 11 is met because Christensen teaches sequences with ornithine. Claims 14 and 17 are met because Christensen teaches C-terminal amidation and N-terminal acylation. Claims 19-21 and 25 are met because Christensen teaches SEQ ID NOs: 3-10. Claim 28 is met because Christensen teaches that Cav-1 can be capped with amidation or acylation. Claims 38-40 and 42 are met because Christensen teaches that the compositions can be administered via inhalation or nebulization. Claims 53-54 are met because Christensen teaches that the composition may also comprise chloroquine in a pharmaceutically acceptable carrier.
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, 2, 5, 7, 11, 14, 17, 19-21, 25, 28, 31, 38-40, 42 and 53-55 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 5, 7, 9, 14, 18, 20, 21, 24-26, 30, 33, 34, 36,43-45, 47 and 58-62 of copending Application No. 18/002,420 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of ‘420 teaches a method of treating or preventing a pathogen-induced lung injury in a subject, wherein the injury is cause by coronavirus, and claim 9 teaches that it is COVID-19, which meets the limitations of instant claims 1, 2 and 4. Claim 7 is met by claim 14 of ‘420 teaching D- and -L-amino acids. Claim 11 is met by claims 18 and 20 teaching ornithine as the non-standard amino acid. Claims 14 and 17 are met by claims 21 and 24 teach C-terminal amidation and N-terminal acylation. Claims 19-21 are met by claims 26 and 27 of ‘420 teaching the same Cav-1 sequences. Claim 28 is met by claim 34 teaching and internalization sequence. Claim 31 is met because acylation and amidation are terminal caps. Claims 38-40 and 42 are met because claims 44 and 47 teach administration by nebulization or inhalation. Claims 53-55 are met by claims 58-60 teaching the same additional therapeutic agents in a pharmaceutical formulation.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 2, 5, 7, 11, 14, 17, 19-21, 25, 28, 31, 38-40, 42 and 53-55 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of U.S. Patent No. 12,479,431 in view of Glassberg Csete.
The claims of ‘431 teach:
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The difference between the prior art and the instant claims is that the prior art does not teach that subject has or has previously had COVID-19.
Glassberg Csete teaches that COVID-19 can present as an asymptomatic carrier state, acute respiratory disease, and pneumonia. Adults represent the population with the highest infection rate; however, neonates, children, and elderly patients can also be infected by SARS-CoV-2. In addition, nosocomial infection of hospitalized patients and healthcare workers, and viral transmission from asymptomatic carriers are possible [0044]. This reference teaches that a method of using Cav-1 as both a diagnostic and therapeutic candidate for diagnosing and optimizing long term health and therapeutic benefit in a susceptible subject with an acute lung injury progressive to pulmonary fibrosis caused by viral infection, including SARS-CoV, CoVID-19, MERS and other viral respiratory diseases [0287]. This reference further teaches that the severe infection with a respiratory virus, including COVID-19, comprises an acute lung injury, acute respiratory distress syndrome, or both [0612]. This reference teaches that antifibrotic Cav-1 protein expression is reduced in mouse model of pulmonary fibrosis [0370]. Christensen teaches that the methods include administering a therapeutic amount of a pharmaceutical composition comprising extracellular vesicles (EVs) comprising one or more miRNAs and a pharmaceutically acceptable carrier [Abstract]. This reference teaches that The ASC exosomes treated punches also show an increase in anti-fibrotic Cav-1 (FIG. 23D) compared to the control [0370-0372; FIG. 23C].
It would have been obvious to one of ordinary skill in the art at the filing date of the invention to have taken the method of ‘431 and administered the Cav-1 peptides to a subject that has or has recovered from COVID-19 because Glassberg Csete teaches that the same lungs conditions treatable with Cav-1 are also effects of COVID-19 infections. One would be motivated to administer the same Cav-1 proteins of ‘431 to the same patient class of those having or susceptible to pulmonary fibrosis or other lung injuries, but who also currently have or have had COVID-19 because Glassberg Csete teaches that COVID-19 infections cause lung injuries and fibrosis. As such, there is a reasonable expectation of success that the method of treating or inhibiting lung injuries and fibrosis with the Cav-1 peptides of ‘431 will be effective in the patient class of those susceptible to post infection fibrosis and lung injuries.
Claims 1-2 are met because ‘431 and Glassberg Csete provide motivation to administer Cav-1 peptides to subjects who have had COVID-19, and who are either currently infected or postinfection. As such, administering Cav-1 during or after COVID-19 infection to treat and prevent lung fibrosis and injuries, as well as the plethora of conditions associated with PACS, is rendered obvious. Claim 5 is met because both references teach treating pulmonary fibrosis and lung injuries. Claim 7 is met because ‘431 teaches D- and L- amino acids. Claim 11 is met because ‘431 teaches sequences with ornithine. Claims 14 and 17 are met because ‘431 teaches C-terminal amidation and N-terminal acylation. Claims 19-21 and 25 are met because ‘431 teaches SEQ ID NOs: 3-10. Claim 28 is met because ‘431 teaches that Cav-1 can be capped with amidation or acylation. Claims 38-40 and 42 are met because ‘431 teaches that the compositions can be administered via inhalation or nebulization. Claims 53-54 are met because ‘431 teaches that the composition may also comprise chloroquine in a pharmaceutically acceptable carrier.
Claims 1, 2, 5, 7, 11, 14, 17, 19-21, 25, 28, 31, 38-40, 42 and 53-55 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. 12,280,089 in view of Glassberg Csete.
The claims of ‘089 teach:
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The difference between the prior art and the instant claims is that the prior art does not teach that subject has or has previously had COVID-19.
The teachings of Glassberg have been described supra.
For the same reasons discussed in the prior art and foregoing NSDP rejections, Glassberg Csete renders it obvious to treat post-acute COVID-19 with the Cav-1 peptides of ‘979.
For the same reasons above, Christensen meets the limitations of all of the claimed Cav-1 modifications and variations, rendering them obvious.
Claims 1, 2, 5, 7, 11, 14, 17, 19-21, 25, 28, 31, 38-40, 42 and 53-55 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of copending Application No. 19/207,979 (reference application) in view of Glassberg Csete and Christensen.
The claims of ‘979 teach:
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The difference between the prior art and the instant claims is that the prior art does not teach that subject has or has previously had COVID-19.
The teachings of Glassberg have been described supra.
For the same reasons discussed in the prior art and foregoing NSDP rejections, Glassberg Csete renders it obvious to treat post-acute COVID-19 with the Cav-1 peptides of ‘979.
For the same reasons above, Christensen meets the limitations of all of the claimed Cav-1 modifications and variations, rendering them obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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.
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/JEANETTE M LIEB/Primary Examiner, Art Unit 1654
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