FINAL 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 .
Applicant’s response filed December 22, 2025 is acknowledged. Claims 1-2, 6, 14-15, 30, 41, 43 and 47 have been amended. Claims 17-29, 31-40, 42, 44-48 and 50 have been canceled. Claims 1-16, 30, 41, 43 and 49 are under examination.
Rejections Withdrawn
The rejection of claims 1, 8-12 and 16 under 35 U.S.C. 102(a)(1) as anticipated by Nerkamp et al (WO 2012/171541 A1) has been withdrawn in light of Applicant’s amendments.
The rejection of claims 1, 6-7, 13, 16, 30, 41 and 49 under 35 U.S.C. 102(a)(1) as anticipated by Schonfeld et al (WO 2012/031744 A1) has been withdrawn in light of Applicant’s amendments.
Rejections Maintained
Claim Rejections - 35 USC § 103
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.
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.
Claims 1-5 and 7-16 are rejected under 35 U.S.C. 103 as being unpatentable over Nerkamp et al. (WO 2012/171541 A1 published December 20, 2012) and view of Lei et al Nature Communications published April 24, 2020).
Claim 1. A fusion polypeptide comprising: a pathogen recognition domain; a linker region; and an interferon domain, wherein the pathogen recognition domain comprises an angiotensin-converting enzyme-2 (ACE2), APN, NRP1, DPP4, CD329 (SIGLEC-9), CD206 (MMR), CD209 (DC-SIGN), CD299 (L-SIGN), or CD301 domain.
Claim 2. The fusion polypeptide of claim 1, wherein the pathogen recognition domain comprises an ACE2 domain.
Claim 3. The fusion polypeptide of claim 2, wherein the ACE2 domain is a soluble form of the ACE2 domain.
Claim 4. The fusion polypeptide of claim 3, wherein the soluble form of the ACE2 domain comprises a truncated form of the soluble form of the ACE2 domain.
Claim 5. The fusion polypeptide of claim 2, wherein the ACE2 domain is enzymatically inactive.
Claim 7. The fusion polypeptide of claim 1, wherein the pathogen recognition domain is an antibody or antibody fragment domain.
Claim 8. The fusion polypeptide of claim 1, wherein the interferon domain is a Type I, Type II, or Type III interferon domain.
Claim 9. The fusion polypeptide of claim 1, wherein the interferon domain is a human interferon domain.
Claim 10. The fusion polypeptide of claim 9, wherein the human interferon domain is a human IFN-3 domain.
Claim 11. The fusion polypeptide of claim 1, wherein the N-terminal of the fusion polypeptide comprises the pathogen recognition domain.
Claim 12. (The fusion polypeptide of claim 1, wherein the N-terminal of the fusion polypeptide comprises the interferon domain.
Claim 13. The fusion polypeptide of claim 1, wherein the pathogen recognition domain binds to a viral surface antigen.
Claim 14. The fusion polypeptide of claim 13, wherein the viral surface antigen is a SARS CoV-2 surface antigen.
Claim 15. The fusion polypeptide of claim 13, wherein viral surface antigen is a SARS CoV-2
Claim 16. A pharmaceutical composition comprising the fusion polypeptide of claim 1.
Nerkamp et al teach fusion proteins comprising interferons or biologically active muteins thereof (see the Abstract). Nerkamp et al teach that the invention is also directed to pharmaceutical compositions comprising a pharmaceutically acceptable carrier in combination with such fusion proteins (see the Abstract).Nerkamp et al teach ubiquitin fusion protein comprising, essentially consisting of or consisting the following parts (i) a interferon or biologically active mutein thereof; (ii) a modified heterodimeric ubiquitin that is capable of binding to a target molecule and (iii) optionally a linker (page 6). Nerkamp et al teach that the preferred interferon is alpha or beta (page 20). Nerkamp et al that the preferred target molecules are proteins and more specifically antigenic epitopes present on proteins (page 11). Nerkamp et al teach an advantage of multimerization of differently modified ubiquitin monomers in order to generate heteromultimeric binding proteins with binding activity lies in the increase of the total number of amino acid residues that can be modified to generate a new affinity binding property to a target molecule (page 12). Nerkamp et al teach a “head-to-tail” fusion is to be understood as fusing the C-terminus of the first protein to the N-terminus of the second protein. In this head-to-tail fusion, the ubiquitin monomers may be connected directly with any linker or alternatively, the fusion of ubiquitin monomers can be Nerkamp et al performed via linkers (pages 13-14). Nerkamp et al teach that the ubiquitin is preferably from mammals (e.g. humans) (page 15). Nerkamp et al teach the order of the parts of the fusion protein from the N-terminus to the C-terminus is as follows: I, preferably IFN-alpha or biologically active mutein thereof – linker – modified heterodimeric ubiquitin protein. Alternatively, the order of the parts of the fusion protein from the N-terminus to the C-terminus is as follows: modified heterodimeric ubiquitin protein – linker – IFN biologically active mutein thereof (page 23). Nerkamp et al teach that the fusion proteins of their invention are advantageous as compared to antibodies and pharmaceutically active components that they exhibit an improved activity, enhanced stability and increased biological half-life in the body as a pharmaceutically active component with an interferon component (page 6).
Nerkamp et al do not specifically teach an angiotensin-converting enzyme-2 (ACE2).
Lei teach a recombinant protein by connecting the extracellular domain of human ACE2 to the FC region of the human immunoglobulin IgG1 and a fusion protein containing an ACE2 mutant (see the Abstract). Lei et al teach that both fusion proteins neutralize virus pseudotyped with SAR-CoV or SARS-CoV-2 spiked proteins in vitro (see the Abstract). Lei et al teach that these fusion proteins exhibit cross-reactivity against coronaviruses, they have potential applications in the diagnosis, prophylaxis and treatment of Sar-CoV-2 (see the Abstract). SARS-CoV-2 necessarily recognizes pathogen recognition domains such as NRP1. Lei et al teach that these ACE2 fusion proteins could also be used as research agents in the development of vaccines and inhibitors (page 3, right column).
It would be prima facie obvious at the time the invention was made to use the ACE2 domain as taught by Lei in the fusion proteins of Nerkamp et al because Nerkamp et al teach that the fusion proteins of their invention are advantageous as compared to antibodies and pharmaceutically active components that they exhibit an improved activity, enhanced stability and increased biological half-life in the body as a pharmaceutically active component with an interferon component (page 6) and Lei et al teach that these fusion proteins exhibit cross-reactivity against coronaviruses, they have potential applications in the diagnosis, prophylaxis and treatment of Sar-CoV-2 (see the Abstract) and these ACE2 fusion proteins could also be used as research agents in the development of vaccines and inhibitors (page 3, right column).
Additionally, KSR International Co. v. Teleflex Inc., 127 Sor. Ct. 1727, 1741 (2007), discloses combining prior art elements according to known methods to yield predictable results, thus the combination is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "The combination of familiar element according to known methods is likely to be obvious when it does no more than yield predictable results". The combination would have yielded a reasonable expectation of success along with predictable results to one of ordinary skill in the art at the time of the invention. Thus, it would have been obvious to a person of ordinary skill in the art to combine prior art elements according to known methods that is ready for improvement to yield predictable results. The claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Applicant’s Arguments
A. Applicant urges that Nerkamp fails to teach a fusion polypeptide comprising the pathogen recognition domains of independent claim 1 as amended and that Nerkamp fails to specifically teach ACE2. However, the action submits that Lei teach a recombinant protein including the extracellular domain of human ACE2 to the FC region of human IgG1 and a fusion comprising an ACE mutant as uses thereof and alleges that it would have been prima facie obvious at the time the invention was made to use the ACE2 domain as taught by Lei in the fusion proteins of Nerkamp because Nerkamp teaches that fusion proteins are advantageous as compared to antibodies and pharmaceutically active components that they exhibit an improved activity, enhanced stability and increased biological half-life in the body as a pharmaceutically active component with an interferon component and Lei et al teach that these fusion proteins exhibit cross-reactivity against coronaviruses, they have potential applications in the diagnosis, prophylaxis and treatment of Sar-CoV-2 and these ACE2 fusion proteins could also be used as research agents in the development of vaccines and inhibitors.
B. In establishing a case of prima facie obviousness, the ultimate determination of patentability is based on the entire record, by a preponderance of evidence, with due consideration to the persuasiveness of any arguments and any evidence properly made of record. Applicant urges that the In re Oetiker 977 F.2d 1443, 24 USPQ2d 1443 (Fed.Cir. 1992). The legal standard of “a preponderance of evidence” requires the evidence to be more convincing than the evidence which is offered in opposition to it. With regard to the rejections under 35 U.S.C. 103, the examiner must provide evidence which as a whole shows that the legal determination sought to be proved (i.e. prima facie case of obviousness has been established) is more probable than not (MPEP 2142).
Response to Applicant’s Arguments
A. The amended claims filed December 22, 2025 are drawn to a fusion polypeptide comprising a pathogen recognition domain; a linker region and an interferon domain, where in the pathogen recognition domain comprises an angiotensin-converting enzyme-2 ACE2), APN, NRP1, DPP4, CD329 (SIGLEC-9), CD206 (MMR), CD209 (DC-SIGN), CD299 (L-SIGN), or CD301 domain. Applicant's arguments filed December 22, 2025 have been fully considered but they are not persuasive.
As stated in the previous office action, Nerkamp et al teach fusion proteins comprising interferons or biologically active muteins, to specifically include interferon. Nerkamp et al teach that the preferred interferon is alpha or beta and the preferred target molecules are proteins and more specifically antigenic epitopes present on proteins. Nerkamp et al do not specifically teach an angiotensin-converting enzyme-2 (ACE2). Lei teach a recombinant protein by connecting the extracellular domain of human ACE2 to the FC region of the human immunoglobulin IgG1 and a fusion protein containing an ACE2 mutant. It would be prima facie obvious at the time the invention was made to use the ACE2 domain as taught by Lei in the fusion proteins of Nerkamp et al because Nerkamp et al teach that the fusion proteins of their invention are advantageous as compared to antibodies and pharmaceutically active components that they exhibit an improved activity, enhanced stability and increased biological half-life in the body as a pharmaceutically active component with an interferon component and Lei et al teach that these fusion proteins exhibit cross-reactivity against coronaviruses, they have potential applications in the diagnosis, prophylaxis and treatment of Sar-CoV-2 and these ACE2 fusion proteins could also be used as research agents in the development of vaccines and inhibitors. The combination of prior art references teach the claimed invention.
Applicant's arguments fail to comply with 37 CFR 1.111(b) because they amount to a general allegation that the claims define a patentable invention without specifically pointing out how the language of the claims patentably distinguishes them from the references.
B. In response to Applicant' s arguments the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). The Examiner has presented evidence just as probable or even more probable as Applicant. In this case, the Examiner has established a prima facie case of obviousness.
6. Claims 30, 41, 43 and 49 are rejected under 103 as being unpatentable over are Nerkamp et al and Lei et al as applied to claims 1-5 and 7-16 above and further in view of Schonfeld et al (WO 2012/031744 A1 published March 15, 2012).
Claim 30. A method of treating a viral infection comprising administering a therapeutically effective amount of the fusion polypeptide of claim 1 to a subject in need thereof.
Claim 41. The method o
Claim 43. The method of claim 41, wherein the viral infection comprises an infection SARS CoV-2.
Claim 49. The method of claim 30, wherein the viral infection comprises an infection with an Influenza virus or an infection with HIV.
The teachings of Nerkamp et al and Lei et al have been described previously.
Nerkamp et al and Lei et al method of treating a subject in need thereof comprising administering a therapeutically amount of the fusion polypeptide or a method of treating a viral infection comprising administering a therapeutically effective amount of the fusion polypeptide wherein the viral infection comprises an infection with influenza virus or HIV.
Schonfeld et al a multi-domain protein comprising a signal peptide, a target specific recognition domain, a linker region and an effector domain (page 3) Schonfeld et al teach the signal peptide at the N-terminus (page 6). Schonfeld et al teach a method of treatment of diseases administering to a subject in a therapeutically effective amount a multi-functional protein, a nucleic acid, an expression construct or a host cell in particular an antigen-specific effector cell (page 20). Schonfeld et al teach a protein comprising a signal peptide, a target specific recognition domain and a linker region (claim 1). Schonfeld et al teach that the target is a virus which includes HIV and Influenza virus (page 6-7). Schonfeld et al teach that preferably, the target antigen is a lineage-specific or tissue-specific tissue antigen including but not limited to CD3, CD4, CD8, CD24, CD25, CD33, CD34, CD133, CD138, CTLA-4, B7-1 (CD80), B7-2 (CD86), endoglin, a histocompatibility complex (MHC) molecule (page 7).
It would be prima facie obvious at the time the invention was made to use the IFN-AC2 fusion proteins as taught by Nerkamp et al and Lei et al above in the method of treating of Schonfeld et al because Nerkamp et al teach that the fusion proteins of their invention are advantageous as compared to antibodies and pharmaceutically active components that they exhibit an improved activity, enhanced stability and increased biological half-life in the body as a pharmaceutically active component with an interferon component (page 6), Lei et al teach that these fusion proteins exhibit cross-reactivity against coronaviruses, they have potential applications in the diagnosis, prophylaxis and treatment of Sar-CoV-2 (see the Abstract). Lei et al teach that these ACE2 fusion proteins could also be used as research agents in the development of vaccines and inhibitors (page 3, right column). Additionally, Schonfeld et al teach a method of treatment of diseases administering to a subject in a therapeutically effective amount a multi-functional protein with a reasonable expectation of success.
Additionally, KSR International Co. v. Teleflex Inc., 127 Sor. Ct. 1727, 1741 (2007), discloses combining prior art elements according to known methods to yield predictable results, thus the combination is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "The combination of familiar element according to known methods is likely to be obvious when it does no more than yield predictable results". The combination would have yielded a reasonable expectation of success along with predictable results to one of ordinary skill in the art at the time of the invention. Thus, it would have been obvious to a person of ordinary skill in the art to combine prior art elements according to known methods that is ready for improvement to yield predictable results. The claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Applicant’s Arguments
In view of the teachings of Geggel and the prior art of record taken as a whole, Applicant submits that it would not have been prima facie obvious at the time of the invention for at least the reason present above to use IFN-ACE2 fusion proteins in a method of treating a viral infection, and more particularly, for treating SARS CoV-2 of the instant claims as amended herein.
Response to Applicant’s Arguments
Applicant's arguments filed December 22, 2025 have been fully considered but they are not persuasive. Applicant is reminded that it is the combination of references that teaches the claimed invention.
The rejection teaches that It would be prima facie obvious at the time the invention was made to use the IFN-AC2 fusion proteins as taught by Nerkamp et al and Lei et al above in the method of treating of Schonfeld et al because Nerkamp et al teach that the fusion proteins of their invention are advantageous as compared to antibodies and pharmaceutically active components that they exhibit an improved activity, enhanced stability and increased biological half-life in the body as a pharmaceutically active component with an interferon component, Lei et al teach that these fusion proteins exhibit cross-reactivity against coronaviruses, they have potential applications in the diagnosis, prophylaxis and treatment of Sar-CoV-2. Lei et al teach that these ACE2 fusion proteins could also be used as research agents in the development of vaccines and inhibitors. Additionally, Schonfeld et al teach a method of treatment of diseases administering to a subject in a therapeutically effective amount a multi-functional protein with a reasonable expectation of success.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). It should be noted that Geggel is not used in this particular rejection.
7. Claims 1, 7-13, 16, 30, 41 and 49 are rejected under 35 U.S.C. 103 as being unpatentable over Nerkamp et al. (WO 2012/171541 A1 published December 20, 2012) in view of Schonfeld et al. (WO 2012/031744 A1 published March 15, 2012).
Claim 1. A fusion polypeptide comprising: a pathogen recognition domain; a linker region; and an interferon domain, wherein the pathogen recognition domain comprises an angiotensin-converting enzyme-2 (ACE2), APN, NRP1, DPP4, CD329 (SIGLEC-9), CD206 (MMR), CD209 (DC-SIGN), CD299 (L-SIGN), or CD301 domain.
Claim 7. The fusion polypeptide of claim 1, wherein the pathogen recognition domain is an antibody or antibody fragment domain.
Claim 8. The fusion polypeptide of claim 1, wherein the interferon domain is a Type I, Type II, or Type III interferon domain.
Claim 9. The fusion polypeptide of claim 1, wherein the interferon domain is a human interferon domain.
Claim 10. The fusion polypeptide of claim 9, wherein the human interferon domain is a human IFN-3 domain.
Claim 11. The fusion polypeptide of claim 1, wherein the N-terminal of the fusion polypeptide comprises the pathogen recognition domain.
Claim 12. The fusion polypeptide of claim 1, wherein the N-terminal of the fusion polypeptide comprises the interferon domain.
Claim 13. The fusion polypeptide of claim 1, wherein the pathogen recognition domain binds to a viral surface antigen.
Claim 16. A pharmaceutical composition comprising the fusion polypeptide of claim 1.
Claim 30. A method of treating a iral infection comprising administering a therapeutically effective amount of the fusion polypeptide of claim 1 to a subject in need thereof.
Claim 41. The method of claim 30, wherein the viral infection comprises an infection with a Coronaviridae family virus.
Claim 49. The method of claim 30, wherein the viral infection comprises an infection with an Influenza virus or an infection with HIV.
Nerkamp et al teach fusion proteins comprising interferons or biologically active muteins thereof (see the Abstract). Nerkamp et al teach that the invention is also directed to pharmaceutical compositions comprising a pharmaceutically acceptable carrier in combination with such fusion proteins (see the Abstract).Nerkamp et al teach ubiquitin fusion protein comprising, essentially consisting of or consisting the following parts (i) a interferon or biologically active mutein thereof; (ii) a modified heterodimeric ubiquitin that is capable of binding to a target molecule and (iii) optionally a linker (page 6). Nerkamp et al teach that the preferred interferon is alpha or beta (page 20). Nerkamp et al that the preferred target molecules are proteins and more specifically antigenic epitopes present on proteins (page 11). Nerkamp et al teach an advantage of multimerization of differently modified ubiquitin monomers in order to generate heteromultimeric binding proteins with binding activity lies in the increase of the total number of amino acid residues that can be modified to generate a new affinity binding property to a target molecule (page 12). Nerkamp et al teach a “head-to-tail” fusion is to be understood as fusing the C-terminus of the first protein to the N-terminus of the second protein. In this head-to-tail fusion, the ubiquitin monomers may be connected directly with any linker or alternatively, the fusion of ubiquitin monomers can be via linkers (pages 13-14). Nerkamp et al teach that the ubiquitin is preferably from mammals (e.g. humans) (page 15). Nerkamp et al teach the order of the parts of the fusion protein from the N-terminus to the C-terminus is as follows: INF, preferably INF-alpha or biologically active mutein thereof – linker – modified heterodimeric ubiquitin protein. Alternatively, the order of the parts of the fusion protein from the N-terminus to the C-terminus is as follows: modified heterodimeric ubiquitin protein – linker – INF biologically active mutein thereof (page 23). Nerkamp et al teach that the fusion proteins of their invention are advantageous as compared to antibodies and pharmaceutically active components that they exhibit an improved activity, enhanced stability and increased biological half-life in the body as a pharmaceutically active component with an interferon component (page 6).
Nerkamp et al do not specifically teach the fusion polypeptide of claim I, a method of treating a viral infection comprising administering a therapeutically effective amount of the fusion polypeptide of claim 1 a subject in need thereof.
Schonfeld et al a multi-domain protein comprising a signal peptide, a target specific recognition domain, a linker region and an effector domain (page 3) Schonfeld et al teach a protein comprising a signal peptide, a target specific recognition domain and a linker region (claim 1). Schonfeld et al teach that the target is a virus which includes HIV and Influenza virus (page 6-7). Schonfeld et al teach that preferably, the target antigen is a lineage-specific or tissue-specific tissue antigen including but not limited to CD3, CD4, CD8, CD24, CD25, CD33, Cd34, CD133, CD138, CTLA-4, B7-1 (CD80), B7-2 (CD86), endoglin, a histocompatibility complex (MHC) molecule (page 7). Schonfeld et al teach a method of treatment of diseases administering to a subject in a therapeutically effective amount a multi-functional protein, a nucleic acid, an expression construct or a host cell in particular an antigen-specific effector cell (page 20).
It would be prima facie obvious at the time the invention was made to use the fusion proteins of Nerkamp et al to recognize specific pathogen domain as taught by Schonfeld et al in the method of treating of Schonfeld et al because Nerkamp et al teach that the fusion proteins of their invention are advantageous as compared to antibodies and pharmaceutically active components that they exhibit an improved activity, enhanced stability and increased biological half-life in the body as a pharmaceutically active component with an interferon component (page 6) and Schonfeld et al teach a method of treatment of diseases administering to a subject in a therapeutically effective amount a multi-functional protein.
Additionally, KSR International Co. v. Teleflex Inc., 127 Sor. Ct. 1727, 1741 (2007), discloses combining prior art elements according to known methods to yield predictable results, thus the combination is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "The combination of familiar element according to known methods is likely to be obvious when it does no more than yield predictable results". The combination would have yielded a reasonable expectation of success along with predictable results to one of ordinary skill in the art at the time of the invention. Thus, it would have been obvious to a person of ordinary skill in the art to combine prior art elements according to known methods that is ready for improvement to yield predictable results. The claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Applicant’s Arguments
Applicant urges that for at least the reasons discussed hereinabove, Nerkamp fails to teach a fusion polypeptide comprising the pathogen recognition domain of independent claim 1 as amended herein, and for at least the reasons set forth hereinabove, Schoenfeld fails to explicitly teach a fusion protein comprising a pathogen recognition domain comprising an ACE2, APN, NRP1, DPP4, CD329 (SIGLEC-9), CD206 (MMR), CD209 (DC-SIGN), CD299 (L-SIGN), or CD301 domain of independent claim 1 as amended herein, and more particularly fail to explicitly teach a pathogen recognition domain comprising an ACE2 domain as set forth in dependent claim 2, or a pathogen recognition domain comprising a CD209 (DC-SIGN), a CD299 (L-SIGN), or a CD301 domain as set forth in dependent claim 6 as amended herein.
In view of the foregoing, Applicant submits that the instant claims are patentable over Nerkamp and Schoenfeld. Withdrawal of the rejection on this basis is respectfully requested.
Response to Applicant’s Arguments
Applicant's arguments filed December 22, 2025 have been fully considered but they are not persuasive. Applicant is reminded that it is the combination of references that teaches the claimed invention.
The rejection teaches that it would be prima facie obvious at the time the invention was made to use the fusion proteins of Nerkamp et al to recognize specific pathogen domain as taught by Schonfeld et al in the method of treating of Schonfeld et al because Nerkamp et al teach that the fusion proteins of their invention are advantageous as compared to antibodies and pharmaceutically active components that they exhibit an improved activity, enhanced stability and increased biological half-life in the body as a pharmaceutically active component with an interferon component (page 6) and Schonfeld et al teach a method of treatment of diseases administering to a subject in a therapeutically effective amount a multi-functional protein.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). It should be noted that claim 6 has been removed from this rejection.
8. Claims are 2-5, 14-15 and 43 rejected under 103 as being unpatentable over Schonfeld et al. (WO 2012/031744 A1 published March 15, 2012) in view Nerkamp et al. (WO 2021/171541 A1 published December 20, 2012) as applied to claims 1, 7-13, 16, 30, 41 and 49 as set forth above and in further view of Geggel (LiveScience published April 24, 2020).
Claim 2. The fusion polypeptide of claim 1, wherein the pathogen recognition domain comprises an ACE2 domain.
Claim 3. The fusion polypeptide of claim 2, wherein the ACE2 domain is a soluble form of the ACE2 domain.
Claim 4. The fusion polypeptide of claim 3, wherein the soluble form of the ACE2 domain comprises a truncated form of the soluble form of the ACE2 domain.
Claim 5. The fusion polypeptide of claim 2, wherein the ACE2 domain is enzymatically inactive.
Claim 14. The fusion polypeptide of claim 13, wherein the viral surface antigen is a SARS CoV-2 surface antigen.
Claim 15. (Currently amended) The fusion polypeptide of claim 13, wherein viral surface antigen is a SARS CoV-2 spike (S) protein.
The teaching of Nerkamp et al and Schonfeld et al have been described previously.
Nerkamp et al and Schonfeld et al do not specifically teach wherein the pathogen recognition domain comprises an angiotensin-converting enzyme-2 (ACE2) domain, wherein the viral surface antigen is a SARS2 surface antigen and
the method of claim 41, wherein the viral infection comprises an infection with Coronaviridae family virus.
Geggel discloses that ACE2 is much more than just a portal for a virus; it plays a critical role in normal lung function and in the circulatory system. Geggel discloses that we have a situation where a virus targets ACE2 as a principal entry route into cells, and at the same time can disable its own normal function. By targeting ACE2, SARS-CoV-2 could be exploiting our own antiviral defenses and tissue-protective responses simultaneously. Geggel discloses that earlier research had revealed that SARS-CoV-2 docks onto cells with ACE2 receptors with the help of an enzyme known as TMPRSS2. This enzyme slices the spike protein of the virus to activate it and allow the virus to enter the cell. Geggel discloses that interferon enhances ACE2 gene expression.
It would be prima facie obvious at the time the invention was made to use the ACE2 and the interferon an as taught by Geggel in the fusion proteins of Nerkamp et al in the method of treating of treating diseases of Schonfeld et al because Nerkamp et al teach that the fusion proteins of their invention are advantageous as compared to antibodies and pharmaceutically active components that they exhibit an improved activity, enhanced stability and increased biological half-life in the body as a pharmaceutically active component with an interferon component (page 6) and discloses that we have a situation where a virus targets ACE2 as a principal entry route into cells, and at the same time can disable its own normal function. Geggel suggests that this feature is important given that interferons are being tested as possible treatment for new coronavirus since it has been shown to contain the virus. Additionally, Geggel et al disclose that interferon enhances ACE2 gene expression and thus, establishes a nexus between ACE2 and interferon with a reasonable expectation of success.
Moreover, KSR International Co. v. Teleflex Inc., 127 Sor. Ct. 1727, t1741 (2007), discloses combining prior art elements according to known methods to yield predictable results, thus the combination is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "The combination of familiar element according to known methods is likely to be obvious when it does no more than yield predictable results". The combination would have yielded a reasonable expectation of success along with predictable results to one of ordinary skill in the art at the time of the invention. Thus, it would have been obvious to a person of ordinary skill in the art to combine prior art elements according to known methods that is ready for improvement to yield predictable results. The claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Applicant’s Arguments
Claims 2-5, 14-15 and 43 stand rejected under 35 U.S.C. § 103 as allegedly being unpatentable over Nerkamp and Schonfeld, and further in view of Live Science to Geggel (hereinafter "Geggel"). See, Item 15, pages 18-20 of the Action. In view of the present amendment, reconsideration is respectfully requested. In view of the teachings of Geggel and the prior art of record when taken as a whole, Applicant submits that it would not have been prima facie obvious at the time of the invention for at least the reasons presented hereinabove to use IFN-ACE2 fusion proteins in a method of treating a viral infection, and more particularly, for treating SARS CoV-2 of the instant claims as amended herein.
As set forth in the Action, Geggel discloses that interferon enhances ACE2 gene expression and thus, establishes a nexus between ACE2 and interferon [for treating SARS CoV-2 with a fusion protein] with a reasonable expectation of success (see, pages 19-20 of the Action). However, Geggel also teach that, "when interferons rush to alert the body to the coronavirus, they're actually stimulating the gene that ramps up expression of ACE2 receptors, which may lead to more ACE2 production and allow SARS-CoV-2 to infect even more cells" (see, page 2 second paragraph of Geggel). While Geggel may disclose that interferons enhance ACE2 gene expression, Geggel also teaches that interferons stimulating expression of ACE2 receptors may also facilitate the infection of more cells with SARS CoV-2. Accordingly, when taken as a whole, and in combination with Nerkamp and Lei, Geggel also teaches away from preparing a fusion polypeptide comprising an ACE2 and an interferon domain, and more particularly, for treating SARS CoV-2 with a reasonable expectation of success.
In view of the foregoing, Applicant submits that the instant claims are patentable over Nerkamp and Schoenfeld and in further view of Geggel. Withdrawal of the rejection on this basis is respectfully requested.
Response to Applicant’s Arguments
Applicant's arguments filed December 22, 2025 have been fully considered but they are not persuasive. Applicant is reminded that it is the combination of references that teaches the claims invention.
The rejection teaches that it would be prima facie obvious at the time the invention was made to use the ACE2 and the interferon an as taught by Geggel in the fusion proteins of Nerkamp et al in the method of treating diseases of Schonfeld et al because Nerkamp et al teach that the fusion proteins of their invention are advantageous as compared to antibodies and pharmaceutically active components that they exhibit an improved activity, enhanced stability and increased biological half-life in the body as a pharmaceutically active component with an interferon component (page 6) and discloses that we have a situation where a virus targets ACE2 as a principal entry route into cells, and at the same time can disable its own normal function. Geggel suggests that this feature is important given that interferons are being tested as possible treatment for new coronavirus since it has been shown to contain the virus. Additionally, Geggel et al disclose that interferon enhances ACE2 gene expression and thus, establishes a nexus between ACE2 and interferon with a reasonable expectation of success.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Geggel also discloses that It might be that in some patients, because of the timing or the dose, interferon can contain the virus, while in others, interferon promotes more infection," Ordovas-Montanes said in a statement. "We want to better understand where the balance lies and how we can maintain a productive antiviral response without producing more target cells for the virus to infect." This finding is important, given that interferons are being tested as a possible treatment for the new coronavirus. Surprisingly, the team found that in primary epithelial cells in the human airway, interferon did lead to more ACE2 gene expression in a dose-dependent fashion. "That is, as you add more interferon, you get more ACE2 expression.” Thus, Geggel et al do not specifically teach away from preparing a fusion protein that includes ACE2. Additionally, Nerkamp et al teach that an advantage associated with fusion proteins of the invention is an enhanced stability in plasma as compared to binding proteins without pharmaceutically active component (e.g. without an interferon part) (page 6).
With regard to rejections under 35 U.S.C. 103 of record, the examiner has provided evidence which as a whole shows that the legal determination sought to be proved (i.e., a prima facie case of obviousness has been established) is more probable than not.
New Ground of Rejection Necessitated by Applicant’s Amendment
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.
9. Claims 1 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Nerkamp et al. (WO 2012/171541 A1 published December 20, 2012) and view of Du et al (Antimicrobial Agents and Chemotherapy, September 2012, Volume 56, Number 9, page 4630-4649).
Claim 1. A fusion polypeptide comprising: a pathogen recognition domain; a linker region; and an interferon domain, wherein the pathogen recognition domain comprises an angiotensin-converting enzyme-2 (ACE2), APN, NRP1, DPP4, CD329 (SIGLEC-9), CD206 (MMR), CD209 (DC-SIGN), CD299 (L-SIGN), or CD301 domain.
Claim 6. The fusion polypeptide of claim 1, wherein the pathogen recognition domain comprises a CD209 (DC-SIGN), aCD299 (L-SIGN), or a CD301 domain.
Nerkamp et al teach fusion proteins comprising interferons or biologically active muteins thereof (see the Abstract). Nerkamp et al teach that the invention is also directed to pharmaceutical compositions comprising a pharmaceutically acceptable carrier in combination with such fusion proteins (see the Abstract).Nerkamp et al teach ubiquitin fusion protein comprising, essentially consisting of or consisting the following parts (i) a interferon or biologically active mutein thereof; (ii) a modified heterodimeric ubiquitin that is capable of binding to a target molecule and (iii) optionally a linker (page 6). Nerkamp et al teach that the preferred interferon is alpha or beta (page 20). Nerkamp et al that the preferred target molecules are proteins and more specifically antigenic epitopes present on proteins (page 11). Nerkamp et al teach an advantage of multimerization of differently modified ubiquitin monomers in order to generate heteromultimeric binding proteins with binding activity lies in the increase of the total number of amino acid residues that can be modified to generate a new affinity binding property to a target molecule (page 12). Nerkamp et al teach a “head-to-tail” fusion is to be understood as fusing the C-terminus of the first protein to the N-terminus of the second protein. In this head-to-tail fusion, the ubiquitin monomers may be connected directly with any linker or alternatively, the fusion of ubiquitin monomers can be via linkers (pages 13-14). Nerkamp et al teach that the ubiquitin is preferably from mammals (e.g. humans) (page 15). Nerkamp et al teach the order of the parts of the fusion protein from the N-terminus to the C-terminus is as follows: INF, preferably INF-alpha or biologically active mutein thereof – linker – modified heterodimeric ubiquitin protein. Alternatively, the order of the parts of the fusion protein from the N-terminus to the C-terminus is as follows: modified heterodimeric ubiquitin protein – linker – INF biologically active mutein thereof (page 23). Nerkamp et al teach that the fusion proteins of their invention are advantageous as compared to antibodies and pharmaceutically active components that they exhibit an improved activity, enhanced stability and increased biological half-life in the body as a pharmaceutically active component with an interferon component (page 6). Nerkamp et al teach that the fusion of their invention can be used in infectious diseases (page 25).
Nerkamp et al do not specifically teach the fusion polypeptide of claim I, wherein the pathogen recognition domain comprises an angiotensin-converting enzyme-2 (ACE2), APN, NRP1, DPP4, CD329 (SIGLEC-9), CD206 (MMR), CD209 (DC-SIGN), CD299 (L-SIGN), or CD301 domain.
However, Du et al teach bifunctional CD4-DC SIGN fusion proteins demonstrate enhanced avidity to gp120 an inhibit HIV-1 Infection and dissemination. Du et al designed constructs by fusing the extracellular CD4 and DC-SIGN domains together with varied arrangements of the lengths of CD4, DC-SIGN and the linker. Du et al expressed, purified and characterized a series of soluble CD4-linker–DCSIGN (CLD) fusion proteins. Several CLDs, composed of a longer linker and an extra neck domain of DC-SIGN, had enhanced affinity for gp120 as evidenced by molecular-interaction analysis. Furthermore, such CLDs exhibited significantly enhanced neutralization activity against both laboratory-adapted and primary HIV-1 isolates. Moreover, CLDs efficiently inhibited HIV-1 infection in trans via a DC-SIGN-expressing cell line and primary human dendritic cells. This was further strengthened by the results from the human cervical explant model, showing that CLDs potently prevented both localized and disseminated infections. Du et al teach that this is the first time that soluble DC-SIGN-based bifunctional proteins have demonstrated anti-HIV potency. Our study provides proof of the concept that targeting both CD4 and DC-SIGN binding sites on gp120 represents a novel antiviral strategy. Given that DC-SIGN binding to gp120 increases exposure of the CD4 binding site and that the soluble forms of CD4 and DCSIGN occur in vivo, further improvement of CLDs may render them potentially useful in prophylaxis or therapeutics (see the Abstract).
It would be prima facie obvious at the time the invention was made to combine the fusion proteins of Nerkamp et al with the CD4-DE-SIGN fusion proteins as taught by Du et al because Nerkamp et al teach that the fusion proteins of their invention are advantageous as compared to antibodies and pharmaceutically active components that they exhibit an improved activity, enhanced stability and increased biological half-life in the body as a pharmaceutically active component with an interferon component and Du et al teach that this is the first time that soluble DC-SIGN-based bifunctional proteins have demonstrated anti-HIV potency. Our study provides proof of the concept that targeting both CD4 and DC-SIGN binding sites on gp120 represents a novel antiviral strategy. Given that DC-SIGN binding to gp120 increases exposure of the CD4 binding site and that the soluble forms of CD4 and DCSIGN occur in vivo, further improvement of CLDs may render them potentially useful in prophylaxis or therapeutics.
Additionally, KSR International Co. v. Teleflex Inc., 127 Sor. Ct. 1727, 1741 (2007), discloses combining prior art elements according to known methods to yield predictable results, thus the combination is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "The combination of familiar element according to known methods is likely to be obvious when it does no more than yield predictable results". The combination would have yielded a reasonable expectation of success along with predictable results to one of ordinary skill in the art at the time of the invention. Thus, it would have been obvious to a person of ordinary skill in the art to combine prior art elements according to known methods that is ready for improvement to yield predictable results. The claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Claim Status
10. .No claims are allowed.
Conclusion
11. 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.
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to VANESSA L. FORD whose telephone number is 571.272.0857. The examiner can normally be reached 8:00-5:00 pm.
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/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674