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 .
Status of Claims
Claims 1-21 are pending.
Claims 18-21 are new.
Claims 1, 2, 5, 6, 10-12, 14, 16 and 17 have been amended by Applicant.
Claims 1-21 are currently under examination in the instant Office Action.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office Action.
This Office Action contains New Rejections Necessitated by Amendments.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 04/06/2026 is being considered by the examiner.
Objections Withdrawn
Specification
Given that Applicant has amended the embedded hyperlink and/or other form of browser-executable code on Pg. 7 Paragraph [0043], the specification objection is now withdrawn.
Claim Rejections Withdrawn
Given that Applicant has amended the claims, the rejection of claims 1-10, 12-13, and 15-17 under AIA 35 U.S.C. 102(a)(1) as being anticipated by NCT04078386 (Record History Version 1 Date Submitted 2019-09-01), as evidenced by PRNewswire (RemeGen Ltd Announcement Nov 15, 2019), Dhillon (Drugs 2021, 81:1671–1675; Published online: 31 August 2021) and International Nonproprietary Names for Pharmaceutical Substances (INN) (Telitacicept in WHO DRUG INFORMATION, VOL.33, NO.3, Year 2019, P.689; provided on the IDS submitted on 03/25/2024 and 11/14/2024) has been withdrawn.
Given that Applicant has amended the claims, the rejection of claims 1-17 under 35 U.S.C. 103 as being unpatentable over NCT04078386 (Record History Version 1 Date Submitted 2019-09-01), PRNewswire (RemeGen Ltd Announcement Nov 15, 2019), Dhillon (Drugs 2021, 81:1671–1675; Published online: 31 August 2021), International Nonproprietary Names for Pharmaceutical Substances (INN) (Telitacicept in WHO DRUG INFORMATION, VOL.33, NO.3, Year 2019, P.689; provided on the IDS submitted on 03/25/2024 and 11/14/2024) and Bird et al. (Curr Opin Rheumatol). 2015 September; 27(5): 461–467) has been withdrawn.
Response to Arguments
In the Reply of 04/06/26, Applicant cites for the 35 U.S.C. 102(a)(1) rejection that to advance prosecution, claim 1 is amended herein to recite that the treatment significantly improves ESSDAI score and/or MF-20 score of the patient. NCT merely teaches a clinical trial protocol without providing any results. Thus, claim 1, as amended, is not anticipated by NCT, as evidenced by PRNewswire, Dhillon, and INN. Claims 2-10, 12-13, and 15-17 all depend from claim 1 and are also not anticipated by NCT, as evidenced by PRNewswire, Dhillon, and INN.
For the 35 U.S.C. 103 rejection, Applicant cites that NCT describes a phase 2 clinical trial protocol designed to examine the efficacy of telitacicept in patients with primary Sjogren's syndrome but does not contain any results demonstrating efficacy. One of skill in the art at the time the instant application was filed would have been aware that clinical trials are unpredictable and drug candidates frequently fail to provide meaningful efficacy. Indeed, only 28.9% of all phase 2 clinical trials proceed to phase 3 and of those 28.9% that do proceed to phase 3, only 57.8% are successful. Thus, the mere fact that a compound has entered into a phase 2 trial can hardly be considered to provide a reasonable expectation that the compound will be successful in treating the indication under exploration.
Further, Applicant cites that PRNewswire, Dhillon, INN, and Bird do not remedy the deficiencies of NCT. PRNewswire and Dhillon both teach that telitacicept demonstrated efficacy in a phase 2 trial for the treatment of SLE and Dhillon teaches that telitacicept was approved for the treatment of SLE in 2021. The Examiner alleged that because Bird teaches that "both SLE and Sjogren's syndrome are autoimmune diseases that share pathogenic function of B cells," one would reasonably expect that telitacicept would be effective for the treatment of primary Sjogren's syndrome based on its efficacy in SLE. Applicant respectfully disagrees. Despite any similarities between SLE and Sjogren's syndrome that Bird described, clinical trials have shown that efficacy for the treatment of SLE does not necessarily correspond to efficacy of the same drug for the treatment of Sjogren's syndrome. For example, another BLyS inhibitor, belimumab is approved for the treatment of SLE but failed to meet the primary endpoint in a phase 2 clinical trial for Sjogren's syndrome and to date, no phase 3 trials have been initiated. Thus, one of skill in the art would not reasonably expect that telitacicept could successfully treat Sjogren's syndrome just because it was shown to be effective for the treatment of SLE.
Applicant argues that accordingly, claim 1 is not obvious over NCT, in view of PRNewswire, Dhillon, INN and Bird. Claims 2-17 all depend from claim 1 and as such, are also not obvious over NCT, in view PRNewswire, Dhillon, INN, and Bird.
Examiner’s Response: The amendments to the claims and the arguments found in the Reply of 04/06/26 have been carefully considered and are deemed persuasive. The 35 U.S.C. 102(a)(1) and 35 U.S.C. 103 rejections have therefore been withdrawn. This is because the claimed method for treating Sjogren’s syndrome (SS) produced treatment outcomes that showed significant improvement in ESSDAI sore and/or MF-20 score which are regarded as unexpected results.
Claim Objection Necessitated by Amendments
Claim 20 appears to have a typographical error. The term “Blys” in line 4 should be amended to “BLys”. Appropriate correction is required.
Claim 9 is objected to as being dependent on a rejected base claim (claim 1; see rejections 112(a) below).
Rejections Necessitated by Amendments
Claim Rejections 35 U.S.C.112(a) – Necessitated by Amendments
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-8 and 10-21 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
In the instant case, claims 1-8 and 10-19 are inclusive of a genus of TACI-Fc fusion proteins that comprises (i) any part of a TACI extracellular region or a fragment thereof that binds to BLyS and/or APRIL; and (ii) any fragment of human immunoglobulin constant region, for a method for treating SS, wherein administering a therapeutically effective amount of said TACI-Fc fusion protein to a patient with SS significantly improves ESSDAI score and/or MF-20 score of the patient.
Note that claim 2 recites “an amino acid sequence set-forth in SEQ ID NO: 1” – any two consecutive amino acids of SEQ ID NO: 1 is “an” amino acid sequence set-forth in SEQ ID NO: 1. Therefore, claims 3 to 7 which are dependents of claim 2, also carry this limitation. In fact, claim 7 recites a similar phrase of “an amino acid sequence set-forth in SEQ ID NO: 3”. Further, claim 8 also recites another similar phrase of “an amino acid sequence set-forth in SEQ ID NO: 4”. It is suggested that amendments to claim 2 be made to delete the phrase “an amino acid sequence set forth in” so that the claim recites “The method according to claim 1, wherein the TACI extracellular region or the fragment thereof that binds to BLyS and/or APRIL comprises SEQ ID NO: 1.” Similar amendments are suggested to delete the phrase “an amino acid sequence set forth in” for claims 3 and 7. As for claim 8, it is suggested that the phrase “has an amino acid sequence set forth in SEQ ID NO: 4” be amended to “comprises SEQ ID NO: 4” such that the claim recites “The method according to claim 1, wherein the TACI-Fc fusion protein comprises SEQ ID NO: 4.
In addition, claims 20-21 are inclusive of a genus of TACI-Fc fusion protein that comprises (i) any part of a TACI extracellular region or a fragment thereof that binds to BLyS and/or APRIL; and (ii) any fragment of human immunoglobulin constant region, for a method for treating pSS, wherein the patient met the 2016 ACR/EULAR classification criteria for pSS.
However, the written description in this case only sets forth ONE SPECIES in the specification as disclosed in paragraphs [0016] and [0043] that the instantly claimed TACI-Fc fusion protein is Telitacicept, and has an amino acid sequence set forth in SEQ ID NO: 4. Therefore, the specification does not disclose, and the art does not teach, the genus of TACI-Fc fusion protein as broadly as they are currently encompassed in the claims.
A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or by describing structural features common to that genus that “constitute a substantial portion of the genus.” See University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997): “A description of a genus of cDNAs may be achieved by means of a recitation of a representative number of cDNA, defined by nucleotide sequence, falling within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus.”
The inventions at issue in Lilly were DNA constructs per se, the holdings of that case is also applicable to claims such as those at issue here. Further, disclosure that does not adequately describe a product itself logically cannot adequately describe a method of using that product. See Ariad, 598 F.3d at 1354-55 (“Regardless whether the asserted claims recite a compound, Ariad still must describe some way of performing the claimed methods... the specification must demonstrate that Ariad possessed the claimed methods by sufficiently disclosing molecules capable of reducing NF-kB activity so as to ‘satisfy the inventor’s obligation to disclose the technologic knowledge upon which the patent is based, and to demonstrate that the patentee was in possession of the invention that is claimed.’”) (internal citation omitted); see also Univ. of Rochester v. G.D. Searle& Co., Inc., 358 F.3d916,918 (Fed.Cir.2004) (applying the same analysis to assess written description for claims to a “method for selectively inhibiting” a particular enzyme by administering a functionally defined compound, i.e., a “non-steroidal compound that selectively inhibits activity” of the gene product for that enzyme).
In regards to claims to a product defined by function, without a correlation between structure and function, the claim does little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 at1568 USPQ2d at 1406 (“definition by function…does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is”).
The instant specification fails to provide sufficient descriptive information, such as definitive structural features that are common to the genus. That is, the specification provides neither a representative number of TACI-Fc fusion proteins that encompass the genus of TACI-Fc fusion proteins for treating Sjogren’s syndrome that can significantly improve ESSDAI score and/or MF-20 score of the patient administered with the said fusion protein; or the genus of TACI-Fc fusion protein for treating pSS, wherein the patient met the 2016 ACR/EULAR classification criteria for pSS; nor does it provide a description of structural features that are common to the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus. “[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A “representative number of species” means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species.
One of ordinary skill in the art would recognize that the specificity and function of a fusion protein is dependent upon the binding regions and effector regions of the fusion protein. The state of the art for TACI-Fc fusion proteins is provided by Hartung et al. (Ther Adv Neurol Disord 2010 Jul;3(4):205-16) which teaches atacicept, a human recombinant fusion that comprises the extracellular ligand-binding domain of the naturally occurring TACI receptor, linked to a recombinant Fc domain of human immunoglobulin (Figure 1). They teach that atacicept binds to BLyS and APRIL on their cognate receptors, and has been shown to neutralize all forms of BLyS and APRIL homo/heterotrimers, inhibiting their effects on B-cell survival and key B-cell functions (see section on “Mechanism of action of atacicept” and Figure 3). They also teach that the efficacy of atacicept has been demonstrated in animal models for autoimmune diseases and the biological activity of atacicept in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) has been demonstrated, which includes clinical studies done to investigate the safety, tolerability and efficacy of atacicept in patients with multiple sclerosis (MS), however an unexpected increase in inflammatory activity in one of the trials led to suspension of all atacicept trials in MS. (Abstract).
Further, Shi et al. (Immunopharmacology and Immunotoxicology, 43(6), 666–673; Published online: 14 Sep 2021) teaches that while atacicept is the most extensively investigated compound targeting soluble and membrane-bound forms of both BAFF and APRIL, telitacicept is another recombinant fusion protein that comprises the ligand-binding domain of the TACI receptor and the Fc component of human IgG (Introduction fourth paragraph and section “Telitacicept: a novel recombinant fusion protein targeting on BLyS/APRIL”). They teach that telitacicept contains a longer TACI fragment than atacicept, and which could significantly reduce circulating B cells, proinflammatory cytokines, and immunoglobulin levels (section “Telitacicept: a novel recombinant fusion protein targeting on BLyS/APRIL” and Figure 1). They also teach that telitacicept has been approved in China to treat SLE while efficacy and safety in patients with RA have been studied but poor clinical response was demonstrated (Abstract and section “Therapeutic efficacy of telitacicept in the clinical study - RA”). Therefore, the differences in the TACI fragment of the TACI-Fc fusion proteins between atacicept and telitacicept and their divergent efficacies in different diseases indicate that variation in the TACI fragment would not predict their function equivalently, which in turn would also not be able to predict the applicability for treating Sjogren’s syndrome as recited in the instant claims as well as the unexpected significantly improved ESSDAI and/or MD-20 scores as recited in instant claims.
Therefore, there is insufficient evidence or nexus that would lead the skilled artisan to predict the ability of TACI-Fc fusion protein that comprises any part of the TACI extracellular region to bind to BLyS and/or APRIL for a method for treating Sjogren’s syndrome that would significantly improve ESSDAI and/or MF-20 score of a patient administered with a therapeutically effective amount of any TACI-Fc fusion protein.
Since the disclosure fails to describe common attributes or characteristics that adequately identify members of the genus, and because the genus is highly variant, the disclosure of ONE SPECIES disclosed in the specification is insufficient to describe the genus. Thus, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus as broadly claimed.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). As discussed above, even though Applicant may propose methods of screening for possible members of the genus, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolation. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. See Ariad, 94 USPQ2d at 1161; Centocor at 1876 (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”)
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Claim Rejections 35 U.S.C.112(a) – Necessitated by Amendments
Claims 1-8 and 10-21 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating SS or pSS, comprising administering a therapeutically effective amount of a TACI-Fc fusion protein that is telitacicept to a patient with SS or pSS, wherein the treatment significantly improves ESSDAI score and/or MF-20 score of the patient, or wherein the patient met the 2016 ACR/EULAR classification criteria for pSS, does not reasonably provide enablement for a method of treating SS or pSS, comprising administering a therapeutically effective amount of any TACI-Fc fusion protein that comprises (i) any part of a TACI extracellular region or a fragment thereof that binds to BLyS and/or APRIL; and (ii) any fragment of human immunoglobulin constant region, to a patient with SS or pSS, wherein the treatment significantly improves ESSDAI score and/or MF-20 score of the patient; or wherein the patient met the 2016 ACR/EULAR classification criteria for pSS. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required are summarized in Ex parte Forman, 230 USPQ 546 (BPAI 1986). They include the nature of the invention, the state of the prior art, the relative skill of those in the art, the amount of direction or guidance disclosed in the specification, the presence or absence of working examples, the predictability or unpredictability of the art, the breadth of the claims, and the quantity of experimentation which would be required in order to practice the invention as claimed.
The above instant claims are drawn to TACI-Fc fusion proteins that comprise (i) a TACI extracellular region or a fragment thereof that has the ability to bind to BLyS and/or APRIL; and (ii) a fragment of human immunoglobulin constant region, that together when linked as a fusion protein and when administered to a patient with SS or pSS as a method for treating SS or pSS, significantly improves ESSDAI score and/or MF-20 score of the patient, or wherein the patient met the 2016 ACR/EULAR classification criteria for pSS.
Note that claim 2 recites “an amino acid sequence set-forth in SEQ ID NO: 1” – any two consecutive amino acids of SEQ ID NO: 1 is “an” amino acid sequence set-forth in SEQ ID NO: 1. Therefore, claims 3 to 7 which are dependents of claim 2, also carry this limitation. In fact, claim 7 recites a similar phrase of “an amino acid sequence set-forth in SEQ ID NO: 3”. Further, claim 8 also recites another similar phrase of “an amino acid sequence set-forth in SEQ ID NO: 4”. It is suggested that amendments to claim 2 be made to delete the phrase “an amino acid sequence set forth in” so that the claim recites “The method according to claim 1, wherein the TACI extracellular region or the fragment thereof that binds to BLyS and/or APRIL comprises SEQ ID NO: 1.” Similar amendments are suggested to delete the phrase “an amino acid sequence set forth in” for claims 3 and 7. As for claim 8, it is suggested that the phrase “has an amino acid sequence set forth in SEQ ID NO: 4” be amended to “comprises SEQ ID NO: 4” such that the claim recites “The method according to claim 1, wherein the TACI-Fc fusion protein comprises SEQ ID NO: 4.
The nature of the invention
The above claims are drawn to fusion proteins comprising a TACI extracellular region or a fragment thereof that can bind BLyS and/or APRIL, that when attached to a fragment of human immunoglobulin constant region and administered to patients, is able to provide superior treatment outcomes in patients with SS as recited in claim 1 for a method for treating SS; or is administered to a specific population of patients with pSS for a method of treating pSS.
This invention is in a class of invention which the CAFC has characterized as "the unpredictable arts such as chemistry and biology". Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
The breadth of the claims
The claims are broad in that they encompass TACI extracellular region or a fragment thereof that can be any truncation or fragment of the TACI extracellular region that which still possesses the function of binding to Blys and/or APIRL and which would perform the method of treating SS with intended outcomes or would perform the method of treating a specific patient population that meets recited criteria for pSS.
The amount of direction provided by the inventor/the existence of working examples
The specification at most discloses one species as outlined in paragraphs [0016] and [0043] that the instantly claimed TACI-Fc fusion protein is Telitacicept that has an amino acid sequence set forth in SEQ ID NO: 4.
However, these teachings do not enable the full breadth of the claims because a fragment of the TACI extracellular region that can be any region or truncation of the full intact extracellular region would not predictably be capable of binding to the target of BLys and/or APIRL and when attached to any fragment of the human immunoglobulin constant region would perform the claimed method of treating a patient with SS or pSS.
The state of the art/the level of predictability in the art
The state of the art teaches that the specificity and function of a fusion protein is dependent upon the binding regions and effector regions of the fusion protein. With regards to TACI-Fc fusion proteins, Hartung et al. (Ther Adv Neurol Disord 2010 Jul;3(4):205-16) teaches atacicept, a human recombinant fusion that comprises the extracellular ligand-binding domain of the naturally occurring TACI receptor, linked to a recombinant Fc domain of human immunoglobulin (Figure 1). They teach that atacicept binds to BLyS and APRIL on their cognate receptors, and has been shown to neutralize all forms of BLyS and APRIL homo/heterotrimers, inhibiting their effects on B-cell survival and key B-cell functions (see section on “Mechanism of action of atacicept” and Figure 3). They also teach that the efficacy of atacicept has been demonstrated in animal models for autoimmune diseases and the biological activity of atacicept in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) has been demonstrated, which includes clinical studies done to investigate the safety, tolerability and efficacy of atacicept in patients with multiple sclerosis (MS), however an unexpected increase in inflammatory activity in one of the trials led to suspension of all atacicept trials in MS. (Abstract).
Further, Shi et al. (Immunopharmacology and Immunotoxicology, 43(6), 666–673; Published online: 14 Sep 2021) teaches that while atacicept is the most extensively investigated compound targeting soluble and membrane-bound forms of both BAFF and APRIL, telitacicept is another recombinant fusion protein that comprises the ligand-binding domain of the TACI receptor and the Fc component of human IgG (Introduction fourth paragraph and section “Telitacicept: a novel recombinant fusion protein targeting on BLyS/APRIL”). They teach that telitacicept contains a longer TACI fragment than atacicept, and which could significantly reduce circulating B cells, proinflammatory cytokines, and immunoglobulin levels (section “Telitacicept: a novel recombinant fusion protein targeting on BLyS/APRIL” and Figure 1). They also teach that telitacicept has been approved in China to treat SLE while efficacy and safety in patients with RA have been studied but poor clinical response was demonstrated (Abstract and section “Therapeutic efficacy of telitacicept in the clinical study - RA”). Therefore, the differences in the TACI fragment of the TACI-Fc fusion proteins between atacicept and telitacicept and their divergent efficacies in different diseases indicate that variation in the TACI fragment would not predict their function equivalently, which in turn would also not be able to predict the applicability for treating Sjogren’s syndrome as recited in the instant claims as well as the unexpected significantly improved ESSDAI and/or MD-20 scores as recited in instant claims.
Therefore, there is insufficient evidence or nexus that would lead the skilled artisan to predict the ability of a TACI-Fc fusion protein to bind to BLys and/or APIRL comprising any fragment of the TACI extracellular region that is attached to any fragment of human immunoglobulin constant region to perform the method of treating a patient with SS or pSS as has been as broadly claimed instantly.
Note that an enabling disclosure for the preparation and use of only a few analogs of a product does not enable all possible analogs where the characteristics of the analogs are unpredictable. See Amgen Inc. v. Chugai Pharmaceutical Co. Ltd. (18 USPQ 2d 1027 (CAFC 1991)).
Not knowing and absent further experimentation, which regions or fragments of TACI extracellular region can retain binding to BLyS and/or APIRL and therapeutically treat subjects with SS or pSS and which regions or fragments cannot do so to perform the method that meets the improved ESSDAI score and/or MF-20 score as broadly claimed, or wherein patient met the 2016 ACR/EUCLAR classification for pSS, even a single change of an encoded amino acid can unpredictably affect structure and function, leads to one having no predictability or expectation of success for the function of any given TACI-Fc fusion protein for a method for treating SS. Such random experimentation to identify at a later time which fragment or truncation or modification is or is not functional and is embraced by Applicant’s claims is undue experimentation.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure
Based on the instant disclosure and prior art, there is no known method through which one of ordinary skill in the art would have been able to reliably predict or otherwise envisage (1) which TACI extracellular fragment retains binding to BLys and/or APRIL; and when fused to (2) which fragment of human immunoglobulin constant region, is able to therapeutically treat subjects with SS or pSS to perform the method wherein the treatment significantly improves ESSDAI score and/or MF-20 score of the patient, or wherein the method is performed in patients that met the 2016 ACR/EULAR classification criteria for pSS.
Therefore, in order to practice the invention as claimed, one of ordinary skill in the art would have to perform undue experimentation to create and function test: (1) different fragments of TACI extracellular region for retention of functional activity that binds BLys and/or APRIL; and (2) different fragments of human immunoglobulin constant region that is fused to the TACI extracellular region, for the method that therapeutically treats subjects with SS or pSS as claimed.
Examiner confirms that Applicant is enabled for the TACI-Fc fusion protein that comprises the TACI extracellular region comprising an amino acid sequence set forth in SEQ ID NO: 1 and the human immunoglobulin comprising an amino acid sequence set forth in SEQ ID NO: 2, or the TACI-Fc fusion protein has an amino acid sequence set forth in SEQ ID NO: 4, or the TACI-Fc fusion protein is Telitacicept, which comprises the amino acid sequence of SEQ ID NO: 4.
Conclusion
One cannot extrapolate the teachings of the specification to the scope of the claims because the claims are broadly drawn to a TACI-Fc fusion protein that comprises any TACI extracellular region or fragment thereof and any fragment of human immunoglobulin constant region, that when administered to a patient with SS at a therapeutically effective amount, significantly improves outcome measures in terms of ESSDAI score and/or MF-20 score of the patient; or is administered to a patient with pSS that met the 2016 ACR/EULAR classification criteria for pSS. Further, Applicant has not enabled TACI-Fc fusion proteins that bind to BLyS and/or APRIL that comprise a TACI extracellular region or fragment other than SEQ ID NO: 1 and comprise a fragment of human immunoglobulin constant region other than SEQ ID NO: 2; or the TACI-Fc fusion protein comprises SEQ ID NO: 4 which is telitacicept, to perform the method as claimed. This is because it has not been shown that any other fragments with different truncation of the TACI extracellular region and any mutations of the human immunoglobulin constant region can perform the method for treating SS or pSS and meet the limitations recited in the above instant claims.
In view of the teachings above and the lack of guidance, workable examples and or exemplification in the specification, it would require an unreasonable amount of experimentation by one of skill in the art to determine with any predictability, that the method would function as claimed. This is because the art teaches that it is unpredictable whether or not other TACI extracellular fragments and other human immunoglobulin constant region variants will function as such, and the specification does not provide direction on which constructs below 100% identity to SEQ ID NO: 4 have function, or do not have function, as claimed in order to perform the method as claimed. In other words, the specification does nothing to ameliorate these concerns over the breadth of the claims rejected above with respect to functional variants, therefore, one would be burdened with undue experimentation to make or use the products of instant claims as broadly as they are currently claimed.
Enablement can be met by amending claim 1 and claim 20 to recite explicitly the amino acid sequences of the TACI-Fc fusion protein and/or the TACI extracellular region or fragment thereof that binds to BLyS and/or APIRL as well as the fragment of human immunoglobulin constant region, that can perform the method as claimed to arrive at the recited outcomes or to be performed in the specific patient population as claimed.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Yie-Chia (Tonya) Lee (Tonya) whose telephone number is (571)272-0123. The examiner can normally be reached Monday - Friday 8.30a - 5.30p Eastern Time Zone.
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/YIE-CHIA LEE (TONYA)/Examiner, Art Unit 1642
/SEAN E AEDER/Primary Examiner, Art Unit 1642
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