jNotice 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
Claims 1-17 are pending.
Claims 1-17 are under examination on the merits.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Claims 1-17 have an effective filing date of 08/01/2024, corresponding to PRO 63/678,350.
Claim Rejections
35 U.S.C. 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.
Claim 14 recites a method of producing a fusion protein of claim 1, said method comprising transiently transfecting a nucleic acid encoding for the fusion protein into a CHO cell, wherein the transfected CHO cell expresses the fusion protein, and wherein the yield of the purified or isolated fusion protein is greater than 50 mg/L in any of the foregoing expression systems. The phrase “greater than 50 mg/L in any of the foregoing expression systems” is ambiguous and unclear. As such one skilled in the art would be unable to readily delineate the metes and bounds of the claim.
Claim 17 is rejected under 35 U.S.C. 112(b), because claim 17 is a “use” claim. According to MPEP 2173.05(q), “[a]ttempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. For example, a claim which read: ‘[a] process for using monoclonal antibodies of claim 4 to isolate and purify human fibroblast interferon’ was held to be indefinite because it merely recites a use without any active, positive steps delimiting how this use is actually practiced. Ex parte Erlich, 3 USPQ2d 1011 (Bd. Pat. App. & Inter. 1986).” Claim 17 recites a fusion protein comprising the sequence of SEQ ID NO: 45 or a pharmaceutical composition thereof for use in treating associated cancers and neurological disorders; however the claim does not recite any active, positive steps defining how this use is actually practiced and is therefore rejected under 35 U.S.C. 112(b).
35 U.S.C. 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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 2, and 5-16 are rejected under 35 U.S.C. 103 as being unpatentable over Nixon et al. (US PG PUB 2013/0323279, publication date: 12/05/2013) in view of Beckman et al. (US PB PUB 2010/0111952, publication date: 05/06/2010) and Kobie et al. (US PG PUB 2020/0140527, publication date: 05/07/2020).
Nixon et al. teach that “[t]he present invention relates to isolated HERV polypeptides, and compositions, including immunogenic compositions, comprising a HERV polypeptide. The present invention provides immunogenic compositions comprising which nucleic acid comprises a nucleotide sequence encoding a HERV polypeptide. Immunogenic compositions are useful for stimulating a T cell immune response to a lentiviral peptide… The present invention additionally provides methods for treating cancer in which HERV polypeptides are expressed. Also provided are methods for treating disorders involving decreased immune response to a HERV polypeptide.” See Abstract. At [0038], Nixon et al. teach that HERV polypeptides include polypeptides encoded by any HERV class or group, e.g., of HERV-W, HERV-H, HERV-K, HERV-L, and HERV-S, and any subgroup thereof (emphasis added).” At [0051], Nixon et al. teach that “[i]n some embodiments, a subject isolated HERV polypeptide is a fusion protein, e.g., a HERV fusion protein comprises a HERV polypeptide covalently linked to a heterologous protein, where the heterologous protein is also referred to as a ‘fusion partner.’”
Based upon the teachings of Nixon et al., one of ordinary skill in the art would have been motivated to prepare a fusion protein that comprises an HERV-K polypeptide, because said fusion protein would at least be useful in the treatment of cancers that express HERV-K polypeptides. Nixon et al. does not teach or suggest a fusion protein comprising a HERV-K Env analog and an Fc fragment, wherein the HERV-K Env analog and the Fc fragment are connected by a peptide linker, wherein the HERV-K (HML-2) Env analog comprises SEQ ID NO: 24. These deficiencies are remedied by Beckman et al. and Kobie et al.
Beckman et al. teach that fusion proteins may be prepared to comprise an Fc region, which may improve “a pharmacodynamic or pharmacokinetic parameter, such as solubility or half-life.” See [0130]. Beckman et al. further teach an Fc region (SEQ ID NO: 22) that may be used to prepare fusion proteins, and SEQ ID NO: 22 comprises the instant SEQ ID NO: 1, as shown below.
Sequence 22, US/12560257A
Publication No. US20100111952A1
GENERAL INFORMATION
APPLICANT: Beckman, Evan
TITLE OF INVENTION: TREATMENT OF AUTOIMMUNE DISORDERS
CURRENT FILING DATE: 2010-01-14
LENGTH: 227
ORGANISM: Homo Sapiens
Query Match - 100.0%; Length - 227; Matches - 226; Mismatches - 0
Qy 1 DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2 DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVD 61
Qy 61 GVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 62 GVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK 121
Qy 121 GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 122 GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS 181
Qy 181 DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 226
||||||||||||||||||||||||||||||||||||||||||||||
Db 182 DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 227
At [0130], Beckman et al. teach that fusion proteins may be prepared to comprise a linker that joins the therapeutic and non-therapeutic domains.
Based upon the teachings of Beckman et al., one of ordinary skill in the art would have been motivated to prepare fusion proteins that comprise an Fc region, such as that of the instant SEQ ID NO: 1, because the addition of said Fc region would reasonably be expected to improve solubility and/or half-life of the fusion protein.
Kobie et al. teach that “HERV-K species, especially the HML-2 clade, is the most recent to enter the human genome, perhaps as recently as 150,000 years ago. There are estimated to be approximately 1000 HERV-K insertions and between 30 and 50 HERV-K proviruses in the human genome. Certain HERV-K loci are capable of expressing all of the viral proteins, and viral particle formation has been detected in teratocarcinoma cell lines. Transcription of HERV-K is strongly affected by apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3G/F (APOBEC3G/F). Under steady state HERV-K genes are not expressed, believed to be the function of suppression mediated in part by APOBEC3G/F. However, in various cancers, upon HIV infection, and other specialized cellular activation methods HERV-K genes are expressed. HERV-K Env expression is activated by malignant transformation, and its expression has been reported in germ cell tumors, melanoma, breast cancer, ovarian cancer, prostate cancer, leukemia and lymphoma.” At [0066], Kobie et al. teach SEQ ID NO 1, which is an HERV-K envelope polypeptide. SEQ ID NO: 1 comprises the instant SEQ ID NO: 24, as shown below.
Sequence 3, US/16328521
Publication No. US20200140527A1
GENERAL INFORMATION
APPLICANT: University of Rochester
APPLICANT: Kobie, James
TITLE OF INVENTION: HUMAN MONOCLONAL ANTIBODIES TO HUMAN ENDOGENOUS RETROVIRUS K ENVELOPE (HERV-K) AND USES THEREOF
CURRENT FILING DATE: 2019-02-26
LENGTH: 367
ORGANISM: Human endogenous retrovirus K
Query Match - 100.0%; Length – 367; Matches - 65; Mismatches - 0
Qy 1 KPPYMLVVGNIVIKPDSQTITCENCRLLTCIDSTFNWQHRILLVRAREGVWIPVSMDRPW 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 298 KPPYMLVVGNIVIKPDSQTITCENCRLLTCIDSTFNWQHRILLVRAREGVWIPVSMDRPW 357
Qy 61 EASPS 65
|||||
Db 358 EASPS 362
One of ordinary skill in the art would have been motivated with a reasonable expectation of success at the effective filing date of the invention to combine the teachings of Nixon et al. with the teachings of Beckman et al. and Kobie et al. to develop a fusion protein comprising a HERV-K Env analog and an Fc fragment, wherein the HERV-K Env analog and the Fc fragment are connected by a peptide linker, wherein the HERV-K (HML-2) Env analog comprises SEQ ID NO: 24. One of ordinary skill in the art would have been motivated to do so, because Nixon et al. teach or suggest a fusion protein that comprises an HERV-K polypeptide. Said fusion protein would at least be useful in the treatment of cancers that express HERV-K polypeptides. Furthermore based upon the teachings of Beckman et al., one of ordinary skill in the art would have been motivated to prepare fusion proteins that comprise an Fc region, such as that of the instant SEQ ID NO: 1, because the addition of said Fc region would reasonably be expected to improve solubility and/or half-life of the fusion protein. By combining the teachings of Nixon et al. and Beckman et al., one of ordinary skill in the art would arrive at a fusion protein comprising a HERV-K Env analog and an Fc fragment, wherein the HERV-K Env analog and the Fc fragment are connected by a peptide linker. Additionally Kobie et al. teach that HERV-K Env expression has been reported in various tumors, and Kobie et al. teach SEQ ID NO 1, which is an HERV-K envelope polypeptide. SEQ ID NO: 1 comprises the instant SEQ ID NO: 24. One of ordinary skill in the art would have been motivated to modify the invention of Nixon et al. and Beckman et al. to comprise the HERV-K Env analog of Kobie et al., which comprises the instant SEQ ID NO: 24, because there would have been a reasonable expectation that the resultant invention - a fusion protein comprising a HERV-K Env analog and an Fc fragment, wherein the HERV-K Env analog and the Fc fragment are connected by a peptide linker, wherein the HERV-K (HML-2) Env analog comprises SEQ ID NO: 24 - is effective in the treatment of cancers that express HERV-K polypeptides. The invention of Nixon et al., Beckman et al., and Kobie et al. meets the limitations of claim 1.
With respect to claim 2, as indicated above, Beckman et al. teach an Fc region (SEQ ID NO: 22) that may be used to prepare fusion proteins, and SEQ ID NO: 22 comprises the instant SEQ ID NO: 1
With respect to claim 5, at [0258] and Table 7, Beckman et al. teach that eliminating N-terminal glycosylation of the Fc region of a fusion protein may reduce protein heterogeneity, which is advantageous; however eliminating glycosylation sites also significantly reduced the expression of the desired protein in culture, which is not advantageous. As such one of ordinary skill in the art would have been motivated to prepare multiple versions of the claimed fusion protein, wherein the Fc portion is either glycosylated or non-glycosylated, in order to determine which level of glycosylation provides the desired balance between protein heterogeneity and fusion protein expression.
With respect to claims 6 and 7, at [0071], Nixon et al. teach that “[t]he immunogenic compositions to be administered are provided in a pharmaceutically acceptable diluent such as an aqueous solution, e.g., a saline solution, a semi-solid form (e.g., gel), or in powder form. Such diluents can be inert, although a subject HERV composition may also include an adjuvant. Examples of known suitable adjuvants that can be used in humans include, but are not necessarily limited to, alum, aluminum phosphate, aluminum hydroxide…”
With respect to claim 8, it would have been prima facie obvious at the effective filing date of the invention to administer the invention of Nixon et al., Beckman et al., and Kobie et al. to individuals having HERV-K-expressing cancers. The fusion protein of Nixon et al., Beckman et al., and Kobie et al. would reasonably be expected to generate T cells that are specific for HERV-K and would provide a therapeutic benefit. This is evidenced at [0079] of Nixon et al. – “The present invention provides an immunogenic composition comprising a HERV polynucleotide, e.g., a polynucleotide comprising a nucleotide sequence encoding a HERV polypeptide. When administered to an individual in need thereof, the polynucleotide (the ‘HERV polynucleotide’) comprising a nucleotide sequence encoding a HERV polypeptide is taken up by a cell, e.g., an antigen-presenting cell, the encoded HERV polypeptide is produced in the cell, and the HERV polypeptide is processed into epitope-displaying polypeptide fragments (‘epitope fragments’) that are then displayed on the surface of the cell in association with an MHC molecule. The encoded HERV polypeptide stimulates or enhances a T cell response to the epitope(s) displayed on the cell surface.” As indicated above at [0071], Nixon et al. teach that immunogenic HERV-K polypeptides may be administered in combination with an adjuvant, and at [0071], Nixon et al. teach that “[t]he effectiveness of an adjuvant may be determined by measuring the amount of antibodies directed against the immunogenic antigen.” As such the administration of the fusion protein of Nixon et al., Beckman et al., and Kobie et al. in combination with a known suitable adjuvant would be expected to elicit the production of antibodies directed against HERV-K, thus meeting the limitations of claims 8 and 13.
With respect to claim 9, as indicated above the administration of the fusion protein of Nixon et al., Beckman et al., and Kobie et al. in combination with a known suitable adjuvant would be expected to elicit the production of antibodies directed against HERV-K. These antibodies would be expected to provide a therapeutic benefit, at least due to the effector functions associated with antibodies directed against an antigen. As such one of ordinary skill in the art would have had ample motivation to administer the invention of Nixon et al., Beckman et al., and Kobie et al. to individuals that are anti-HERV-K antibody naïve.
With respect to claim 10, it would have also been prima facie obvious to administer the invention of Nixon et al., Beckman et al., and Kobie et al. to individuals that have measurable anti-HERV-K antibody titers prior to the administration of the fusion protein, because many individuals having measurable anti-HERV-K antibody titers would have low titers. For these individuals, the administration of the invention of Nixon et al., Beckman et al., and Kobie et al. would reasonably be expected to improve anti-HERV-K antibody titers, thus providing a therapeutic benefit. Furthermore it would have also been prima facie obvious to administer the invention of Nixon et al., Beckman et al., and Kobie et al. to individuals that have measurable anti-HERV-K antibody titers prior to the administration of the fusion protein, because said invention would be expected to elicit therapeutic anti-HERV-K T cell responses.
With respect to claims 11 and 12, at [0187], Beckman et al. teach that fusion proteins comprising Fc regions may be formulated for subcutaneous or intramuscular administration, which generally involves administration via injection.
With respect to claims 14-16, at [0157], Beckman et al. teach that fusion proteins may be produced in mammalian cell culture, such as CHO cells, and Beckman et al. teach host cells that express fusion proteins, wherein the host cell comprises a vector that comprises a nucleic acid encoding said fusion protein, wherein said host cell is a CHO cell. One of ordinary skill in the art would appreciate that one well-known means of introducing a vector comprising a nucleic acid of interest into a host cell is via transfection with either RNA or, typically, cDNA that encodes a protein of interest, such as a fusion protein. Therefore one of ordinary skill in the art would have been motivated to prepare the fusion protein of Nixon et al., Beckman et al., and Kobie et al. by introducing a nucleic acid encoding said fusion protein into a vector, which may then be transfected into CHO cells and cultured to yield said fusion protein. Therefore the limitations of claims 14-16 were prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention.
As such the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention, as evidenced by the references.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Nixon et al. (US PG PUB 2013/0323279, publication date: 12/05/2013) in view of Beckman et al. (US PB PUB 2010/0111952, publication date: 05/06/2010) and Kobie et al. (US PG PUB 2020/0140527, publication date: 05/07/2020), as applied to claims 1, 2, and 5-16, and further in view of Lazar et al. (US PG PUB 2005/0054832, publication date: 03/10/2005).
As indicated above one of ordinary skill in the art would have been motivated with a reasonable expectation of success at the effective filing date of the invention to combine the teachings of Nixon et al., Beckman et al., and Kobie et al. to develop a fusion protein comprising a HERV-K Env analog and an Fc fragment, wherein the HERV-K Env analog and the Fc fragment are connected by a peptide linker, wherein the HERV-K (HML-2) Env analog comprises SEQ ID NO: 24. These references do not teach a GGGSGGGS linker. This deficiency is remedied by Lazar et al.
At [0118], Lazar et al. teach that Fc fusion proteins may be prepared using peptide linkers - “Preferably, the linker is from about 1 to 30 amino acids in length, with linkers of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 19 and 20 amino acids in length being preferred. In addition, the amino acid residues selected for inclusion in the linker peptide should exhibit properties that do not interfere significantly with the activity of the polypeptide. Thus, the linker peptide on the whole should not exhibit a charge that would be inconsistent with the activity of the polypeptide, or interfere with internal folding, or form bonds or other interactions with amino acid residues in one or more of the monomers that would seriously impede the binding of receptor monomer domains. Useful linkers include glycine-serine polymers (including, for example, (GS)n, (GSGGS)n (GGGGS)n and (GGGS)n, where n is an integer of at least one), glycine-alanine polymers, alanine-serine polymers, and other flexible linkers…”
Based upon the teachings of Lazar, one of ordinary skill in the art would appreciate that flexible linkers, such as (GGGS)n, wherein n is more than one and the linker is 8 amino acids in length, may be used to prepare Fc fusion proteins.
One of ordinary skill in the art would have been motivated with a reasonable expectation of success at the effective filing date of the invention to combine the teachings of Nixon et al., Beckman et al., Kobie et al. to develop a fusion protein comprising a HERV-K Env analog and an Fc fragment, wherein the HERV-K Env analog and the Fc fragment are connected by a peptide linker, wherein the HERV-K (HML-2) Env analog comprises SEQ ID NO: 24, and wherein the linker is a GGGSGGGS linker. One of ordinary skill in the art would have been motivated to do so, because one of ordinary skill in the art would have been motivated with a reasonable expectation of success at the effective filing date of the invention to combine the teachings of Nixon et al., Beckman et al., and Kobie et al. to develop a fusion protein comprising a HERV-K Env analog and an Fc fragment, wherein the HERV-K Env analog and the Fc fragment are connected by a peptide linker, wherein the HERV-K (HML-2) Env analog comprises SEQ ID NO: 24. Furthermore based upon the teachings of Lazar, one of ordinary skill in the art would appreciate that flexible linkers, such as (GGGS)n, wherein n is more than one and the linker is 8 amino acids in length, may be used to prepare Fc fusion proteins. One of ordinary skill in the art would have had ample motivation to prepare the fusion protein of Nixon et al., Beckman et al., and Kobie et al. to comprise a flexible (GGGS)2 linker between the HERV-K Env analog component and the Fc fragment, because such a modification would result in a HERV-K Env analog/Fc fusion protein that may be used to treat cancers that express HERV-K.
As such the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention, as evidenced by the references.
Allowable Subject Matter
Claim 4 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NELSON B MOSELEY II whose telephone number is (571)272-6221. The examiner can normally be reached on M-F, 9:00-6:00 EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis, can be reached at 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642