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 .
Detailed Action
The Amendments and Remarks filed 9/30/25 in response to the Office Action of 7/14/25 are acknowledged and have been entered.
Claims 12-13 have been added by Applicant.
Claims 1, 2, 5-7, and 9-13 are pending.
Claims 1 and 5-7 have been amended by Applicant.
Claims 1, 2, 5-7, and 9-13 are currently under examination.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Rejections Withdrawn
The rejection of claims under 35 U.S.C. 103(a) as being unpatentable over Ulrichts et al (US 2016/0264669 A1; 9/15/16) in view of Dirchwolf et al (World J Hepatol, 2015, 7(16): 1974-1981) and Patil et al (ISBT Science Series, 2013, 8: 185-188) is withdrawn.
The rejection of claims under 35 U.S.C. 103 as being unpatentable over Ulrichts et al (US 2016/0264669 A1; 9/15/16) in view of Dirchwolf et al (World J Hepatol, 2015, 7(16): 1974-1981) and Patil et al (ISBT Science Series, 2013, 8: 185-188) and Freeman et al (Journal of Viral Hepatitis, 2003, 10, 285-293) is withdrawn.
The rejections under 35 U.S.C. 112, first paragraph, are withdrawn.
Rejections Maintained
Claim Rejections - 35 USC § 103
Claims 1, 2, 5-7, 9, and 11 remain rejected and claims 12-13 are rejected under 35 U.S.C. 103(a) as being unpatentable over Surowy et al (WO 2009/009019 A2; 1/15/09) in view of Dirchwolf et al (World J Hepatol, 2015, 7(16): 1974-1981) and Castaño et al (Science Translational Medicine, 2009, 1(5): 1-11).
Surowy et al teaches a method of treating subjects with a fibrosis related disorder comprising administering a therapeutically effective amount of a C reactive protein (CRP) antagonist or a therapeutically effective amount of a serum amyloid P (SAP) agonist (see “The anti-fibrotic therapy may include CRP antagonists and/or SAP agonists…” at first full paragraph on page 3; also see “The treatment plan may comprise the administration of an SAP agonist or CRP agonist or combination thereof.” at first full paragraph on page 5, in particular). Surowy et al further teaches said method wherein the fibrosis related disorder is liver cirrhosis (first full paragraph on page 53, in particular), including alcohol induced cirrhosis (sixth paragraph on page 54, in particular). Surowy et al further teaches said method wherein the fibrosis related disorder is a result of chronic hepatitis B or C infection (second full paragraph on page 53, in particular). Surowy et al further teaches said method wherein the SAP agonist is an anti-FcgRIIA antibody/immunoglobulin, an aggregated IgG antibody, or a cross-linked IgG antibody (third full paragraph on page 3, in particular), including wherein the antibody/immunoglobulin has an Fc region (second and third full paragraph on page 40), and including an anti-FCgRIIA F(ab’)2 fragment (third full paragraph on page 40, in particular). Surowy et al further teaches (a) SAP agonist anti-FcgR antibody/immunoglobulin and (b) SAP agonist aggregated antibodies as distinct SAP agonists where the anti-FcgR antibody/immunoglobulin bind FcgR using variable regions (and not Fc domains) and the aggregated antibodies bind FcgR using Fc domains (see section “(ii)” on page 39 and section “(iii)” on page 40, in particular). Each anti-FcgRIIA antibody/immunoglobulins of Surowy et al is a “ligand of FcgRIIA” and is “capable of inducing LC3-associated phagocytosis” (LAP), as evidenced by the instant specification and acknowledges on page 6 of the Reply of 7/26/24. Surowy et al further teaches the anti-FcgRIIA antibody/immunoglobulin can be “any isotype”, including IgG, (fourth full paragraph on page 39, in particular) and one of skill in the art would recognize (a) the anti-FcgRIIA antibody/immunoglobulin of Surowy et al are “ligand” of FcgRIIA (as defined by lines 9-11 on page 6 of the instant specification) and (b) IgG, IgE, and IgD antibody isotypes are monomeric and IgA antibody isotype is dimeric. Surowy et al further teaches said method wherein the administered SAP agonist is formulated with a physiologically acceptable carrier (first full paragraph on page 56, in particular).
Surowy et al does not specifically teach the subjects with cirrhosis have acute-on-chronic liver failure or “sustained inflammation”. However, these deficiencies are made up in the teachings of Dirchwolf et al and Castaño et al.
Dirchwolf et al teaches cirrhosis can be divided into an initial stage, known as compensated cirrhosis, and an advanced stage which includes acute-on-chronic liver failure (ACLF) (Abstract, in particular). Dirchwolf et al further teaches cirrhosis patients often exhibit systemic inflammatory response syndrome (SIRS) and that SIRS is associated with dysfunction in cirrhosis patients and with outcome of ACLF (left column on page 1975, in particular). Dirchwolf et al further teaches such systemic inflammation occurs as a consequence of persistent immune cell activation (right column on page 1975, in particular). Such inflammation is “sustained inflammation.” Dirchwolf et al further teaches such inflammation is an “underlying mechanism” of ACLF (left column on page 1977, in particular).
Castaño et al teaches SAP triggers an anti-inflammatory signature in infiltrating macrophages (page 6, in particular). Castaño et al further teaches SAP-mediated inhibition of mouse kidney fibrosis corelates with binding of SAP to cell debris and with subsequent suppression of inflammatory monocytes and kidney macrophages in vitro and in vivo (Abstract, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method comprising the method of Surowy et al, wherein a therapeutically effective amount of a SAP agonist (such as anti-FcgRIIA IgG or anti-FCgRIIA F(ab’)2 fragment of Surowy et al) is the only active agent administered with the physiologically acceptable carrier of Surowy et al, to treat just a subject with a fibrosis related disorder, such as a subject of Dirchwolf et al with acute-on-chronic liver failure (ACLF) and/or cirrhosis having systemic and/or sustained inflammation, wherein the inflammation is treated by administering a therapeutically effective amount of just any SAP agonist of Surowy et al because the method of Surowy et al treats cirrhosis by administering a SAP agonist and Castaño et al teaches SAP triggers an anti-inflammatory signature in infiltrating macrophages and SAP-mediated inhibition of mouse kidney fibrosis corelates with binding of SAP to cell debris and with subsequent suppression of inflammatory monocytes and kidney macrophages in vitro and in vivo. This is an example of some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to combine prior art refence teachings to arrive at the claimed invention.
Further, anti-FcgRIIA antibody/immunoglobulins of Surowy et al is a “ligand of FcgRIIA” and is “capable of inducing LC3-associated phagocytosis” (LAP), as evidenced by the instant specification and acknowledges on page 6 of the Reply of 7/26/24.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Response to Arguments
In the Reply of 9/30/25, Applicant cites lines 13-19 on page 9 of Surowy et al and page 4 of Pilling et al (J Leukocyte Biol PMC, 2015, 1-23) and argues Surowy et al does not teach administering monomeric or dimeric ligand of FCgRIIA.
The amendments to the claims and the arguments found in the Reply of 9/30/25 have been carefully considered, but are not deemed persuasive. In regards to the citation of lines 13-19 on page 9 of Surowy et al and page 4 of Pilling et al (J Leukocyte Biol PMC, 2015, 1-23) and argument Surowy et al does not teach administering monomeric or dimeric ligand of FCgRIIA, the examiner disagrees. Lines 13-16 on page 9 of Surrowy et al teach FcgR are activated by aggregated IgG and it has been shown that aggregated, but not monomeric, human IgG inhibits human fibrocyte, fibrocyte precursor, myofibroblast precursor, and/or hematopoietic monocyte precursor differentiation. Lines 16-19 on page 9 of Surrowy et al further teaches monoclonal antibodies that bind FcgRII “also” inhibit fibrocyte, fibrocyte precursor, myofibroblast precursor, and/or hematopoietic monocyte precursor differentiation. Further, the cross-linked IgG antibodies used by Pilling et al to inhibit fibrocyte differentiation are “human IgG” and are not anti-FcgR IgG. Monoclonal antibodies that bind FcgRII and anti-FcgR IgG (which bind FcgR using antibody variable regions and not using Fc regions; see fourth full paragraph on page 39 of Surowy et al) are not the same as aggregated IgG or cross-linked IgG (which interact with FcgR using Fc regions of the aggregated IgG or cross-linked IgG; see third full paragraph on page 2 of Pilling et al and see “Aggregated IgG lacking Fc domains or aggregated IgA, IgE, or IgM do not inhibit fibrocyte, fibrocyte precursor, myofibroblast precursor, and/or hematopoietic monocyte precursor differentiation” at lines 18-20 on page 9 of Surowy et al). SAP agonist anti-FcgR antibody/immunoglobulin of Surowy et and the aggregated antibodies of Surowy et are two different types of SAP agonists. Surowy et al teaches (a) SAP agonist anti-FcgR antibody/immunoglobulin and (b) SAP agonist aggregated antibodies as distinct SAP agonists where the anti-FcgR antibody/immunoglobulin bind FcgR using variable regions (and not Fc domains) and the aggregated antibodies bind FcgR using Fc domains (see section “(ii)” on page 39 and section “(iii)” on page 40, in particular). Surowy et al further teaches the anti-FcgRIIA antibody/immunoglobulin can be “any isotype”, including IgG, (fourth full paragraph on page 39, in particular) and one of skill in the art would recognize (a) the anti-FcgRIIA antibody/immunoglobulin of Surowy et al are “ligand” of FcgRIIA (as defined by lines 9-11 on page 6 of the instant specification) and (b) IgG, IgE, and IgD antibody isotypes are monomeric and IgA antibody isotype is dimeric.
Claim Rejections - 35 USC § 103
Claim(s) 1, 2, 5-7, and 9-11 remain rejected and claims 12-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Surowy et al (WO 2009/009019 A2; 1/15/09) in view of Dirchwolf et al (World J Hepatol, 2015, 7(16): 1974-1981) and Castaño et al (Science Translational Medicine, 2009, 1(5): 1-11) as applied to claims 1, 2, 5-7, 9, and 11-13 above, and further in view of Freeman et al (Journal of Viral Hepatitis, 2003, 10, 285-293).
Teachings of Surowy et al, Dirchwolf et al, and Castaño et al are discussed above.
Surowy et al, Dirchwolf et al, and Castaño et al do not specifically describe a subject with cirrhosis that is caused by chronic hepatitis. However, these deficiencies are made up in the teachings of Freeman et al.
Freeman et al teaches chronic hepatitis C virus infection progresses to cirrhosis (left column on page 285, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of Surowy et al, Dirchwolf et al, and Castaño et al wherein the subject with cirrhosis has cirrhosis that is cause by chronic hepatitis because Surowy et al teaches administering the SAP agonist of the combined method to subjects with the fibrosis related disorder cirrhosis and a fibrosis related disorder that is a result of chronic hepatitis B or C infection and Freeman et al teaches chronic hepatitis C virus infection progresses to cirrhosis. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Response to Arguments
In the Reply of 9/30/25, Applicant repeats arguments addressed above.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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