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 .
Response to Amendment
Applicant’s preliminary amendment filed 20 October 2022 has been received and entered. Claims 3-5, 10-11, 14-19 and 30-38 have been amended and claims 20-29 and 39-40 have been canceled. Claims 1-19 and 30-38 are currently pending and under consideration in the instant Office action.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
The information disclosure statement (IDS) submitted on 20 October 2022 has been considered by the examiner.
NOTE: The citation which is identified only as “Supplemental Table 2” (NPL document item #21) has been lined through as there is no identifying information provided for this document. The information contained therein is meaningless without proper context as to the experimental conditions which were employed to arrive at the data contained in the Table. The citation does not comply with 37 CFR 1.98(b)(5) as there is no identifying information provided.
Specification
The disclosure is objected to because of the following informalities: the specification does not comply with 37 CFR 1.52(a)(1)(iv-v). Portions of the specification are not in dark ink and therefore, not presented in a form having sufficient clarity and contrast between the paper and writing thereon to permit the direct reproduction of readily legible copies by use of optical character recognition. See at least page 2, paragraph 2 of the instant specification (sample is provided below):
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Typically, this type of text is observed when documents are prepared with color or with “track changes” left on, resulting in the “color” being approximated by the system into grayscale. The “color” text is faint and necessary clarity/contrast in order to be compliant with 37 CFR 1.52 is lost. A substitute specification is required which is entirely in black ink/font is required.
Appropriate correction is required.
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. The claims are not directed to antibodies, but rather, methods of treatment.
Claim Rejections - 35 USC § 102
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) 1-2 and 34-35 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Beidler et al. (U.S. Pat. No. 9,783,605).
Beidler et al. teach PAN-ELR+ CXC chemokine antibodies which bind human IL-8 (CXCL8), human Gro-alpha (CXCL1), human Gro-beta (CXCL2), human Gro-gamma (CXCL3), human ENA-78 (CXCL5), human GCP-2 (CXCL6) and NAP-2 (CXCL7). The antibody neutralizes all seven ELR+ CXC chemokines which inhibits CXCR1+ and CXCR2+ cells from migrating to sites of inflammation. The antibody comprises 6 CDRs which have the amino acid sequences of SEQ ID NO:7-12, heavy and light chain variable amino acid sequences of 2 and 4 or 14 and 16, respectively and heavy and light chain amino acid sequences of 1 and 13 or 3 and 15, respectively. See the disclosure of ‘570 at columns 1-2. The antibody of Beidler et al. is the same as the antibody of the instant application.
Beidler et al. stated that the specific binding of and neutralization by the disclosed antibody to hman ELR+ CXC chemokines allows the antibody to be used as a therapeutic for diseases and disorders which benefit from inhibition of human ELR+ CXC chemokine bioactivity (see column 5, lines 43-47). Beidler et al. also teach methods of treatment by administration of the PAN-ELR+ CXC chemokine antibody. Beidler et al. teach the treatment of ulcerative colitis, renal cancer and ovarian cancer (see column 2 and columns 13-16). While Beidler et al. do not describe use of the disclosed antibodies for the purpose of treating acute respiratory distress syndrome (ARDS), the administration of the disclosed antibody in the methods of treating ulcerative colitis, renal cancer and ovarian cancer would result in the prevention of acute respiratory distress syndrome (ARDS). The instant claims recite that the method is performed in a patient in need thereof, however, because ARDS is a life-threatening lung condition characterized by widespread inflammation and damage to the alveoli, any and all patients would be in need thereof. Therefore, the method disclosed and taught in Beidler et al. would inherently result in the prevention of ARDS since the method step of administration is the same.
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.
Claims 1-19 and 30-38 is/are rejected under 35 U.S.C. 103 as being obvious over Zhou (WO 2017/073369) in view of any one of Beidler et al. (U.S. Pat. No. 9,290,570, 9,783,605, 10,093,727, 10,858,425). The specifications of each Beidler et al. patent are identical; the rejection only references ‘570 for the sake of simplicity but the disclosures cited are found in all of the Beidler et al. patents.
Zhou teaches an antibody, referred to as PanELR, which neutralizes human IL-8, Gro-alpha, Gro-beta, Gro-gamma, gcp-2 and ENA-78. These CXC chemokines are known to stimulate neutrophil chemotaxis by activation of the CXCR1 and CXCR2 receptors. PanELR decreases neutrophil chemotaxis through inhibition of CXCR1 and CXCR2 receptor activation by neutralizing the targets to which it binds. Specifically, the antibody suppresses the infiltration of neutrophils in a number of animal models including the LPS inhaled model of lung inflammation and the cantharidin skin blister model. 10 mg/Kg administered i.v. suppresses over 90% of neutrophil infiltration (see page 2, last 2 paragraphs). The inhibition of these CXC chemokines by the PanELR antibody can prevent inflammatory cells from infiltrating the lung tissue and therefore, prevent tissue damage.
Zhou teaches a method of treating a human with diseases or disorders characterized by elevated levels of one or more of human IL-8, Gro-alpha, Gro-beta, Gro-gamma, gcp-2 and ENA-78 with the PanELR antibody. Such conditions include COPD, asthma, acute lung injury, acute lung disease, sepsis, ARDS, neonatal respiratory distress syndrome, respiratory syncytial virus, flu, Bronchiolitis obliterans syndrome and diffuse panbronchiolitis (see page 4). Zhou teaches that the PanELR antibody can be used to treat or prevent the recited diseases/conditions (see page 15, lines 27-28).
Zhou does not teach prevention or treatment of ARDS with an antibody that additionally binds human neutrophil activating protein-2 (CXCL7) and has 6 CDRs with the amino acid sequences of SEQ ID NO:7-12 as recited in the instant claims.
Beidler et al. (U.S. Pat. No. 9,783,605) teach an antibody which binds and neutralizes human IL-8, Gro-alpha, Gro-beta, Gro-gamma, gcp-2, ENA-78 and NAP2 and has 6 CDRs with the amino acid sequences of SEQ ID NO:7-12 (aka Antibody 1). Beidler et al. teach that neutralization of all seven ELR+CXC chemokines inhibits the ability of CXCR1 and CXCR2 positive cells from migrating to sites of inflammation (see column 1). Beidler et al. teach that Antibody 1 neutralizes the chemotaxis ability of neutrophils in vitro (see column 12).
It would have been obvious before the effective filing date of the instant application to prevent or treat ARDS in a subject in need thereof with an antibody that inhibits neutrophil chemotaxis through inhibition of CXCR1 and CXCR2 receptor activation as taught by Zhou. It would have been obvious to one of ordinary skill in the art to substitute the antibody of Beidler et al. for the antibody of Zhou because the antibody of Beidler et al. binds to seven chemokines while the antibody of Zhou only binds six of the chemokines which activate CXCR1 and CXCR2. The substitution would have been obvious because the antibody of Beidler et al. would inactivate more stimulatory chemokines and because Beidler et al. teach that Antibody 1 neutralizes all seven ELR+CXC chemokines and inhibits CXCR1 and CXCR2 positive cell migration. While neither reference specifically discusses patients at risk of ARDS, one of ordinary skill in the art would have known that patients with respiratory insults, disease or injury are those patients at risk of developing ARDS because is an inflammatory lung condition. Additionally, one of ordinary skill in the art would be motivated to treat ARDS in any patient regardless of the degree of the condition (mild, moderate, severe) or the method of diagnosis or what condition precipitated the ARDS (viral infection) because ARDS is a life-threatening lung condition which damages the alveoli and can lead to fluid accumulation in the lungs which impairs oxygen exchange and can result in respiratory failure. It would have been obvious to one of ordinary skill in the art before the effective filing date to treat patients who had been diagnosed by any means, including according to the Berlin definition of ARDS because this definition has been widely adopted by healthcare professionals.
With regard to claims 17-19 and 36-38, neither reference specifically teaches dosages to be administered. However, determination of dosages is routine optimization because the prior art of Zhou and Beidler et al. teach that panELR antibodies are effective to inhibit neutrophil migration and infiltration and determining of optimum or workable ranges of doses would be characterized as routine experimentation in the relevant art as dosage is a result-effective variable. Therefore, the instant claims directed to dosage administration are obvious over the teachings of Zho and Beidler et al.
Claims 1, 6, 17-19 and 36-38 is/are rejected under 35 U.S.C. 103 as being obvious over Zhou (WO 2017/073369) in view of Beidler et al. (U.S. Pat. No. 9,783,605) and further in view of U.S. Pat. No. 12,037,387 (Kikly et al.).
The teachings of Zhou and Beidler et al. are as provided above. Neither teaching discloses the dosages which are recited in claims 17-19 and 36-38.
Kikly et al. teach the administration of the same antibody of Beidler et al. for the treatment of hidradenitis suppurativa wherein the dose is administered either intravenously or subcutaneously in the range of about 100 mg to about 1000 mg, or 150 mg to about 1500 mg, 100-600mg, 300-600mg, 100-150mg, 150-900mg, 450-900mg, 250-450mg, 600-1000mg, 900-1500mg, about 300mg, about 600mg, and about 900mg as well as including a loading dose and administration includes multiple administrations (see claims 4-22 of Kikly et al.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to practice the method of Zhou for the treatment/prevention of ARDS with the antibody of Beidler et al. because it neutralizes seven chemokines rather than the six of Zhou and to further administer the antibody subcutaneously or intravenously at doses in the range of about 100mg to about 1500mg as taught by Kikly et al. because Kikly et al. teach that these dosages are safe and well-tolerated in patients as well as the dosages being effective to inhibit neutrophil chemotaxis and accumulation in a skin blister model (see columns 9-10 beginning at line 32). As the dosages of Kikly et al. were determined to be safe and effective to inhibit neutrophil chemotaxis, it would have been obvious to one of ordinary skill in the art to treat/prevent ARDS as taught by Zhou with the antibody of Beidler et al. using the dosages of Kikly et al. with a reasonable expectation of success because administration with the dosages of Kikly et al. inhibit neutrophil chemotaxis and neutrophil infiltration is the hallmark of ARDS.
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 1-19 and 30-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 and 10-12 of U.S. Patent No. 9,290,570 in view of Zhou (WO 2017/073369). Although the claims at issue are not identical, they are not patentably distinct from each other because the claimed method of preventing/treating ARDS with an antibody which binds and neutralizes human IL-8, Gro-alpha, Gro-beta, Gro-gamma, gcp-2, ENA-78 and NAP2 and has 6 CDRs with the amino acid sequences of SEQ ID NO:7-12 (aka Antibody 1) would have been obvious over the claims of ‘570 directed to the same antibody in view of the teachings of Zhou (WO 2017/073369).
The antibody recited in the methods of the instant claims is identical to that of ‘570. The claims of ‘570 are directed to the PAN-ELR+CXC chemokine antibody called Antibody 1.
The teachings of Zhou are provided above. Briefly, Zhou teach the prevention/treatment of ARDS with a PanELR antibody (neutralizes human IL-8, Gro-alpha, Gro-beta, Gro-gamma, gcp-2 and ENA-78). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to practice the method of Zhou with the antibody of ‘570 because the antibody of ‘570 neutralizes all of the same chemokines as that of Zhou and additionally neutralizes NAP2, an additional chemokine that activates CXCR1 and CXCR2 which are responsible for neutrophil chemotaxis and infiltration of the lungs in ARDS. One would have had a reasonable expectation of success in practicing the method of Zhou with the antibody of ‘570 because the antibody of ‘570 neutralizes human ELR+CXC chemokines and inhibits neutrophil chemotaxis (see columns 11-12 of ‘570).
While neither Zhou nor ‘570 specifically discusses patients at risk of ARDS, one of ordinary skill in the art would have known that patients with respiratory insults, disease or injury are those patients at risk of developing ARDS because is an inflammatory lung condition. Additionally, one of ordinary skill in the art would be motivated to treat ARDS as taught in Zhou in any patient regardless of the degree of the condition (mild, moderate, severe) or the method of diagnosis or what condition precipitated the ARDS (viral infection) because ARDS is a life-threatening lung condition which damages the alveoli and can lead to fluid accumulation in the lungs which impairs oxygen exchange and can result in respiratory failure. It would have been obvious to one of ordinary skill in the art before the effective filing date to treat patients who had been diagnosed by any means, including according to the Berlin definition of ARDS because this definition has been widely adopted by healthcare professionals.
With regard to claims 17-19 and 36-38, neither Zhou nor ‘570 specifically teaches dosages to be administered. However, determination of dosages is routine optimization because the prior art of Zhou and ‘570 teach that panELR antibodies are effective to inhibit neutrophil migration and infiltration and determining of optimum or workable ranges of doses would be characterized as routine experimentation in the relevant art as dosage is a result-effective variable. The instant claims directed to dosage administration are obvious over the teaching of Zhou and the claims of ‘570. Therefore, the instant claims are not patentably distinct from those of ‘570 because the claimed method of treating/preventing ARDS would have been an obvious use in view of Zhou.
Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Grommes et al. Contribution of Neutrophils to Acute Lung Injury. Mol. Med. 17(3-4): 293-307, 2011. Grommes et al. teach that neutrophils are considered to play a key role in the progression of acute lung injury (ALI) and ARDS and that activation and transmigration of neutrophils is a hallmark event in the progression of ALI and ARDS. The concentration of neutrophils in the bronchoalveolar lavage fluid correlates with the severity of ARDS and the outcome (see page 293, column 3).
Boyle et al. Biological therapies in the acute respiratory distress syndrome. Expert Opin. Biol. Ther. 14(7): 969-981, 2014. Boyle et al. teach that ARDS is an inflammatory condition characterized by neutrophil and macrophage-mediated injury, with excessive pro-inflammatory cytokine and protease activity in the alveolar space (see page 969, paragraph 2).
Yang et al. Understanding the role of neutrophils in acute respiratory distress syndrome. Biomedical Journal. 44: 439-446, 2021. Yang et al. teach that neutrophil counts are positively correlated with disease severity in ARDS (see abstract).
Williams et al. Evidence for chemokine synergy during neutrophil migration in ARDS. Thorax. 72: 66-73, 2017. Williams et al. teach that ARDS is a life-threatening condition characterized by pulmonary oedema, respiratory failure and severe inflammation as well as recruitment of neutrophils into the lung interstitium and alveolar space (see abstract).
US Pat. No. 8,496,932 (Clegg et al.). Clegg et al. teach an antibody which binds human IL-8, Gro-alpha, Gro-beta, Gro-gamma and ENA-78 and its use for prevention/treatment of ARDS and other respiratory diseases (see columns 9-10).
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Christine J Saoud whose telephone number is (571)272-0891. The examiner can normally be reached M-F, 6am-2:30pm.
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/Christine J Saoud/Primary Examiner, Art Unit 1645