Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Election/Restrictions
Applicant’s election without traverse of Group I, composition SA100680 of Table 5, SEQ ID NO: 1 (follistatin), and SEQ ID NO: 17 (fetuin A) in the reply filed on 8/28/2026 is acknowledged.
Applicants elected species (i.e. the composition of Table 5) was deemed to be free of the prior art. In accordance with Markush Practice, the search was extended to the Markush group/independent claim, and a reference was discovered that rendered it obvious. As a result, claims 1-7, 10-16 and 30-37 have been examined and claims 8-9, 17-29 and 38-49 are withdrawn from consideration. While applicant’s elected species may read on one or more withdrawn claims, they have not been fully examined for patentability, and thus a determination of allowability cannot be made with respect to these claims at this time. This is proper, as MPEP 803.02 states that, in these circumstances, the prior art search, however, will not be extended unnecessarily to cover all nonelected species (MPEP 803.02).
Status of the Claims
Claims 1-49 are pending in this application.
Claims 8-9, 17-29 and 38-49 are withdrawn from consideration as being drawn to a non-elected species/invention.
Claims 1-7, 10-16 and 30-37 are presently under consideration as being drawn to the elected species/invention.
Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
Claims 13, 15 and 31 are objected to because of the following informalities: Claim 13 should be amended to recite “The pharmaceutical composition of 12, wherein the myogenic antagonist factors further comprise Periostin, TGFb1, IL-6, FGF-21, TGFb2, TNFb, TGFb3, Activin A, TGFa”. Claim 15 should be amended to recite “The pharmaceutical composition of claim 14, wherein the pro-myogenic factors comprise one or more of OPN, IGFBP-4, MMP-1, TSP-1, GROa, MMP-10, bIG-H3, hCGb, RGM- B, VEGF, Cripto-1, HGF, BMP-5, bFGF, IGF-2, PDGF-AA, FGF-19, and WISP-1”. Claim 31 should be amended to recite “The composition of claim 30, wherein the at least two myogenic agonists further comprise OPN, IGFBP-4, MMP-1, TSP-1, GROa (CXCL1), MMP-10,bIG-H3, hCGb, RGM-B, VEGF, Cripto-1, HGF, BMP-5, bFGF, IGF-2, PDGF-AA, FGF-19, WISP-1, or combinations thereof”. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1-6 and 11-16 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are drawn to a pharmaceutical composition comprising (A) a follistatin protein or a variant thereof, and (B) a fetuin A protein (alpha-2-HS-glycoprotein) or a fragment or variant thereof, wherein (B) is capable of binding to TGF-(3, and wherein the total amount of (A) and (B) is greater than about 10% of total proteins in the composition.
When referring to the fragment or variant of fetuin A, the specification teaches that said fragment or variant of fetuin A is capable of binding to TGF-b.
Without a correlation between structure and function, the claims do little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (“A definition by function alone “does not suffice” to sufficiently describe a coding sequence because it is only an indication of what the gene does, rather than what it is”).”
Here, the specification fails to describe what part of the sequence of fetuin A correlates with the required activity (i.e. binding to TGF-b).
The MPEP states that a broad genus can be described by a showing of representative number of examples. The claims in the instant application are broad.
Based on the teachings of the specification, the fragment or variant of fetuin A can be any fragment or variant of the 367 amino acids long fetuin A.
However, the specification fails to provide a representative number of examples for the claimed fragment or variant.
The specification does not provide any teaching of what modifications can be made within the claimed sequence to allow for the claimed function (i.e. binding to TGF-b).
Furthermore, the specification does not provide any teaching of the specific amino acid motifs necessary for the claimed function.
The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming a rejection for lack of written description because the specification does “little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate”).
Therefore, since the specification fails to identify any relevant structural characteristics that can be attributed to the claimed function and activity, the claimed invention lacks written description.
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 16 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 16 recites the limitations “pro-myogenic factors” and “myogenic antagonist factors” in lines 1-2. There is insufficient antecedent basis for this limitation in the claim.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 3 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 3 is drawn to the pharmaceutical composition of claim 2, wherein the variant of the follistatin protein has at least 75% sequence identity to any one of SEQ ID NOS: 1-13. It is noted that claim 1 states that the composition comprises a follistatin protein or a variant. Therefore, since claim 2 is limited to the follistatin protein, claim 3 fails to include all the limitations of claim 2. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-7, 10-16 and 30-37 are rejected under 35 U.S.C. 103 as being unpatentable over Guatam et al. (US 2019/0224277).
With respect to claims 1, 11-13 and 30, Guatam et al. teach a bio-mimetic formulation comprising about 50 to about 200 recombinant peptides (claim 17), or at least about 100 recombinant peptides (claim 18).
It is noted that the bio-mimetic formulation of Guatam et al. comprises a total of 280 recombinant peptides, including follistatin, fetuin A and follistain like-1.
Given the finite possibilities, one of ordinary skill in the art would have arrived at a bio-mimetic formulation comprising follistatin, fetuin A and follistain like-1.
With respect to the claimed amount of follistain and fetuin A (i.e. greater than about 10%, greater than about 20%, or between about 1-20 pmol/mL), and with respect to the claimed amount of myogenic antagonist factors (not more than about 20%), the MPEP 2144.05 A states that “[G]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997)”.
Since Applicant has not disclosed that the specific limitations recited in the instant claims are for any particular purpose or solve any stated problem, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum amount of follistain and fetuin A by normal optimization procedures known in the pharmaceutical art.
With respect to claims 2-7 and 10, Guatam et al. teach that the bio-mimetic formulation is for treating a condition, illness or disease in a human (paras [0165], [0167], [0171], [0173]).
Therefore, one of ordinary skill in the art would have been motivated to use homologous (i.e., human) follistatin and fetuin-A (which correspond to instant SEQ ID NOs: 1 and 17, respectively) to treat human patients, with a reasonable expectation of success in minimizing immune rejection.
It is noted that SEQ ID NO: 1 comprises SEQ ID NO: 14, and SEQ ID NO: 17 comprises SEQ ID NO: 27.
With respect to claims 14-15, 31-32 and 34, the bio-mimetic formulation of Guatam et al. comprises OPN, IGFBP-4, MMP-1, GRO, MMP-10, bIG-H3, hCGb, RGM-B, VEGF, Cripto-1, HGF, BMP-5, bFGF, IGF-2, PDGF-AA, Activin A and TGFb1 (see claim 16 and Table 9).
With respect to claims 16, 33 and 35-37, since Applicant has not disclosed that the specific limitations recited in the instant claims are for any particular purpose or solve any stated problem, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum amount of pro-myogenic factors (i.e. myogenic agonist), myogenic antagonists factors (i.e. myogenic antagonists) by normal optimization procedures known in the pharmaceutical art (see MPEP 2144.05 A).
Claims 1-7, 10-15 and 30-31 are rejected under 35 U.S.C. 103 as being unpatentable over Zuber et al. (US 2008/0089868).
With respect to claims 1, 11-13 and 30, Zuber et al. teach a composition comprising a population of retinal stem cells, said retinal stem cells comprising a population of reprogrammed non-retinal cells (claim 1), wherein the non-retinal cell types are reprogrammed by externally applying or causing the cells to express or over express one or more secreted activator or inhibitor of a signaling pathway involved in retinal stem cell formation (claim 11), wherein said activator or inhibitor is an antagonist of BMP (claim 13), wherein said antagonist of BMP is selected from one or more of the following: (a) fetuin; (b) noggin; ( c) chordin; ( d) gremlin; ( e) follistatin; (f) cerberus; (g) arnnionless; (h) DAN; and (i) the ecto domain of the BMP receptor protein BMRlA (claim 14), and wherein the signaling pathway is TGF-b (claim 16).
Zuber et al. do not specifically teach that fetuin is fetuin A.
However, since there are only two fetuin proteins (i.e. Fetuin A and B), one would have at once envisaged using fetuin A.
With respect to the claimed amount of follistain and fetuin A (i.e. greater than about 10%, or between about 1-20 pmol/mL), the MPEP 2144.05 A states that “[G]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997)”.
Since Applicant has not disclosed that the specific limitations recited in the instant claims are for any particular purpose or solve any stated problem, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum amount of follistain and fetuin A by normal optimization procedures known in the pharmaceutical art.
With respect to claims 2-7 and 10, Zuber et al. teach that the retinal stem cells are human (claim 3).
Therefore, one of ordinary skill in the art would have been motivated to use homologous (i.e., human) follistatin and fetuin-A (which correspond to instant SEQ ID NOs: 1 and 17, respectively) to reprogram human retinal stem cells, with a reasonable expectation of success in minimizing immune rejection.
It is noted that SEQ ID NO: 1 comprises SEQ ID NO: 14, and SEQ ID NO: 17 comprises SEQ ID NO: 27.
With respect to claims 14-15 and 31, the composition Zuber et al. further comprises VEGF (para [0054]).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SERGIO COFFA whose telephone number is (571)270-3022. The examiner can normally be reached M-F: 6AM-4PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MELISSA FISHER can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SERGIO COFFA Ph.D./
Primary Examiner
Art Unit 1658
/SERGIO COFFA/Primary Examiner, Art Unit 1658
