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
This application is a 371 of PCT/US23/61416.
The amendment filed on August 4, 2026 has been entered.
Status of Claims
Claims 1, 5-8, 11, 13-14, 19, 21, 23-28, 31, 33-34, and 38-39 are pending.
Claims 1, 5-8, 11, 13-14, 19, 21, 23-28, 31, 33-34, and 38-39 are under examination.
Response to Amendments/Arguments
Drawings
Applicant’s arguments, see page 6 of the Remarks, filed August 4, 2026, with respect to the drawings have been fully considered and are persuasive. A replacement of FIG.2B has been submitted. Therefore, the objection of the drawings has been withdrawn.
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, 8, 11, 13-14, 19, 21, 23-26, 31, 33-34, and 38-39 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.
MPEP 2111.01 states that ''[d]uring examination, the claims must be interpreted as broadly as their terms reasonably allow.'' Claims 1, 8, 11, 13-14, 19, 21, 23, and 39 have been broadly interpreted to encompass a method of treating or preventing heart failure with preserved ejection fraction (HFpEF) in a subject by administering (1) any FXI polypeptide comprising a functional catalytic domain or (2) or a polynucleotide encoding the FXI polypeptide of (1), wherein the FXI polypeptide additionally modulates the expression or activity of p-Smad1/5. Claims 24-26, 31, and 33-34 have been broadly interpreted to encompass a method of activating the BMP-Smad1/5 pathway in heart tissue by overexpressing (1) any FXI polypeptide comprising a functional catalytic domain or (2) or a polynucleotide encoding the FXI polypeptide of (1). Claim 38 has been broadly interpreted to encompass a method of monitoring the effectiveness of administering a composition comprising an any FXI polypeptide comprising a functional catalytic domain or a polynucleotide encoding any FXI polypeptide in a subjecting having HFpEF by performing a first initial echocardiogram and subsequence echocardiogram. Therefore, the claims are drawn to a method of using a genus of FXI polypeptides having a functional catalytic domain having unknown structure or a genus of polynucleotides encoding FXI polypeptides having unknown structure to (1) treat or prevent HFpEF in a subject, (2) activate BMP-Smad1/5 pathway in heart tissue, and (3) monitoring the effectiveness of the administering of a composition said genus of FXI polypeptide or genus of polynucleotides.
MPEP 2163 I. states that to “satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention.
MPEP 2163. II.A.3.(a) sates that “Possession may be shown in many ways. For example, possession may be shown by describing an actual reduction to practice of the claimed invention. Possession may also be shown by a clear depiction of the invention in detailed drawings or in structural chemical formulas which permit a person skilled in the art to clearly recognize that inventor had possession of the claimed invention. An adequate written description of the invention may be shown by any description of sufficient, relevant, identifying characteristics so long as a person skilled in the art would recognize that the inventor had possession of the claimed invention.
According to MPEP 2163.II.A.3.(a).ii), “Satisfactory disclosure of a ‘representative number’ depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus…Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’"
The recitations of “FXI polypeptide comprising a functional catalytic domain” fail to provide a sufficient description of the genus of the FXI polypeptides/encoded FXI polypeptides used in the claimed method as it merely describes the functional features of the genus without providing any definition of the structural features of the species within the genus. The specification does not specifically define any of the species that fall within the genus. The specification does not define any structural features commonly possessed by members of the genus that distinguish them from others. One skilled in the art therefore cannot, as one can do with a fully described genus, visualize or recognize the identity of the members of the genus.
Zabczyk (Active tissue factor and activated factor XI in circulating blood of patients with systolic heart failure due to ischemic cardiomyopathy. Pol Arch Med Wewn. 2010 Sep;120(9):334-40– form PTO-1449) discloses that elevated clotting factors (FXI) and thrombin generation have been reported to occur in patients with heart failure (abstract). Loeffen (Factor XIa and Thrombin Generation Are Elevated in Patients with Acute Coronary Syndrome and Predict Recurrent Cardiovascular Events. PLoS One. 2016 Jul 15;11(7):e0158355 – form PTO-1449) discloses that ACS (acute coronary syndrome) patients had an enhanced prothrombotic profile, demonstrated by an increased thrombin generation potential, factor XIa and D-dimer levels. This study is the first to demonstrate the positive association between factor XIa, thrombin generation and recurrent cardiovascular events (abstract). A method of using FXI polypeptide comprising a functional catalytic domain or polynucleotide encoding said FXI polypeptide to treat heart failure with preserved ejection fraction (HFpEF) or activate BMP-Smad1/5 pathway in heart tissue was not known in the prior art.
The specification is limited to a method of treating or preventing HFpEF in a subject by administering a FXI polypeptide mutant having the amino acid sequence of SEQ ID NO:43 or 44, monitoring their effectiveness in treating or preventing HfpEF, and activating the BMP-Smad1/5 pathway in heart tissue by overexpressing the FXI polypeptide mutant having the amino acid sequence of SEQ ID NO:43 or 44. While MPEP 2163 acknowledges that in certain situations “one species adequately supports a genus,” it also acknowledges that “[f]or inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus.” In view of the widely variant species encompassed by the genus, the examples described above are not enough and does not constitute a representative number of species to describe the whole genus. Therefore, the specification fails to describe a representative species of the claimed genus.
One of skill in the art could identify variants of FXI. However, there is no teaching regarding which amino acids of any FXI can vary and result in a polypeptide having FXI activity, treating or preventing HfpEF, and/or activate BMP-Smad1/5 pathway in heart tissue.
Fransceus (J Ind Microbiol Biotechnol. 2017 May;44(4-5):687-695. – cited previously on form PTO-892) reviews protein engineering techniques, such as random mutagenesis and recombination, directed evolution and iterative or combinatory saturation “hotspots”. Fransceus states that “a recurring problem, however, is choosing which amino acid positions should be targeted. Answering this question is not an easy feat and requires substantial insight in the relationship between an enzyme’s sequence or structure and its properties.” Sanavia (Computational and Structural Biotechnology Journal, Volume 18, 2020, Pages 1968-1979. – cited previously on form PTO-892) discloses challenges in the prediction of protein stability in the occurrence of multiple mutations. “Multiple-point mutations are common variations of the protein sequence that may be needed in protein engineering when a single-point mutation is not enough to yield the desired stability change. Dealing with multiple-site variations adds another level of complexity beyond the prediction of the effect of a single variant on protein stability, since it requires the learning of many types of combinatorial effects”.
An important consideration is that structure is not necessarily a reliable indicator of function. In the instant case, there is no disclosure relating similarity of structure to conservation of function. Conservation of structure is not necessarily a surrogate for conservation of function.
While general knowledge in the art may have allowed one of skill in the art to identify other polypeptides expected to have the same or similar tertiary structure, there was no general knowledge in the art in the ability of a polypeptide having FXI activity, treating or preventing HFpEF, and/or activate BMP-Smad1/5 pathway in heart tissue. Accordingly, one of skill in the art would not accept the disclosure of the FXI polypeptide having the amino acid sequence of SEQ ID NO:43 or 44 as representative species of a FXI in the claimed method.
Given this lack of description of the representative species encompassed by the genus of the claims, the specification fails to sufficiently describe the claimed invention in such full, clear, concise, and exact terms that a skilled artisan would recognize that applicants were in possession of the inventions of claims 1, 8, 11, 13-14, 19, 21, 23-26, 31, 33-34, and 38-39.
Applicant's arguments filed August 4, 2026 have been fully considered but they are not persuasive.
Applicant argues that the specification sufficiently describes the claimed subject matter because (1) claims 1, 24, and 38 have been amended to recite a FXI polypeptide comprising a functional catalytic domain and (2) the specification provides exemplary FXI polypeptides comprising a functional catalytic domain, such as Example 9 and Table 7.
This is not found persuasive.
The instant claims are not product claims directed to FXI polypeptides or the exemplary FXI polypeptides. Instead, the claims are drawn to a method of using a genus of FXI polypeptides having a functional catalytic domain having unknown structure or a genus of polynucleotides encoding said FXI polypeptides having unknown structure to (1) treat or prevent HFpEF in a subject, (2) activate BMP-Smad1/5 pathway in heart tissue, and (3) monitoring the effectiveness of the administering of a composition said genus of FXI polypeptide or genus of polynucleotides. Example 9 and Table 7 of the instant specification are limited to an intact functional catalytic domain of two FXI polypeptides of SEQ ID NO:43 and 44 and two mutations sites that are necessary for having catalytic activity. The specification does not provide catalytic domains of any FXI polypeptides. While general knowledge in the art may have allowed one of skill in the art to identify other polypeptides expected to have the same or similar tertiary structure, there was no general knowledge in the art in the ability of a FXI polypeptide having unknown structure but having the function of FXI activity, treating or preventing HFpEF, and/or activate BMP-Smad1/5 pathway in heart tissue. Accordingly, one of skill in the art would not accept the disclosure of the FXI polypeptide having the amino acid sequence of SEQ ID NO:43 and 44 as representative species of the FXI used in the claimed method.
The specification is limited to a method of treating or preventing HFpEF in a subject by administering a FXI polypeptide mutant having the amino acid sequence of SEQ ID NO:43 or 44, monitoring their effectiveness in treating or preventing HfpEF, and activating the BMP-Smad1/5 pathway in heart tissue by overexpressing the FXI polypeptide having the amino acid sequence of SEQ ID NO:43 or 44.
As discussed above, Zabczyk (Active tissue factor and activated factor XI in circulating blood of patients with systolic heart failure due to ischemic cardiomyopathy. Pol Arch Med Wewn. 2010 Sep;120(9):334-40– form PTO-1449) discloses that elevated clotting factors (FXI) and thrombin generation have been reported to occur in patients with heart failure (abstract). Loeffen (Factor XIa and Thrombin Generation Are Elevated in Patients with Acute Coronary Syndrome and Predict Recurrent Cardiovascular Events. PLoS One. 2016 Jul 15;11(7):e0158355 – form PTO-1449) discloses that ACS (acute coronary syndrome) patients had an enhanced prothrombotic profile, demonstrated by an increased thrombin generation potential, factor XIa and D-dimer levels. This study is the first to demonstrate the positive association between factor XIa, thrombin generation and recurrent cardiovascular events (abstract). A method of using FXI polypeptide comprising a functional catalytic domain or polynucleotide encoding said FXI polypeptide to treat heart failure with preserved ejection fraction (HFpEF) or activate BMP-Smad1/5 pathway in heart tissue was not known in the prior art.
Therefore, the recitation of “FX1 polypeptide comprising a functional catalytic domain” fail to provide a sufficient description of the genus of the FXI polypeptides/encoded FXI polypeptides used in the claimed method as it merely describes the functional features of the genus without providing any definition of the structural features of the species within the genus.
Hence the rejection has been maintained.
Claims 1, 8, 11, 13-14, 19, 21, 23-26, 31, 33-34, and 38-39are 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 or preventing HFpEF in a subject by administering a FXI polypeptide mutant having the amino acid sequence of SEQ ID NO:43 or 44, monitoring their effectiveness in treating or preventing HfpEF, and activating the BMP-Smad1/5 pathway in heart tissue by overexpressing the FXI polypeptide mutant having the amino acid sequence of SEQ ID NO:43 or 44, does not reasonably provide enablement for a method of using any FXI polypeptide comprising a functional catalytic domain having unknown structure or a genus of polynucleotides encoding said FXI polypeptide to (1) treat or prevent HFpEF in a subject, (2) activate BMP-Smad1/5 pathway in heart tissue, and (3) monitoring the effectiveness of the administering of a composition comprising said any FXI polypeptide or any polynucleotide. 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 In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.
The breadth of the claims.
MPEP 2111.01 states that ''[d]uring examination, the claims must be interpreted as broadly as their terms reasonably allow.'' Claims 1, 8, 11, 13-14, 19, 21, 23, and 39 have been broadly interpreted to encompass a method of treating or preventing heart failure with preserved ejection fraction (HFpEF) in a subject by administering (1) any FXI polypeptide comprising a functional catalytic domain or (2) or a polynucleotide encoding the FXI polypeptide of (1), wherein the FXI polypeptide additionally modulates the expression or activity of p-Smad1/5. Claims 24-26, 31, and 33-34 have been broadly interpreted to encompass a method of activating the BMP-Smad1/5 pathway in heart tissue by overexpressing (1) any FXI polypeptide comprising a functional catalytic domain or (2) or a polynucleotide encoding the FXI polypeptide of (1). Claim 38 has been broadly interpreted to encompass a method of monitoring the effectiveness of administering a composition comprising an any FXI polypeptide comprising a functional catalytic domain or a polynucleotide encoding any FXI polypeptide in a subjecting having HFpEF by performing a first initial echocardiogram and subsequence echocardiogram. Therefore, the claims are drawn to a method of using any FXI polypeptide comprising a functional catalytic domain having unknown structure or a any polynucleotide encoding said FX1 polypeptide to (1) treat or prevent HfpEF in a subject, (2) activate BMP-Smad1/5 pathway in heart tissue, and (3) monitoring the effectiveness of the administering of a composition comprising said any FXI polypeptide or any polynucleotide.
The claim is not commensurate with the enablement provided by the disclosure with regard to the extremely large number of FXI polypeptides and polynucleotides encoding said FXI polypeptides for treating/preventing HFpEF in a subject and/or activating the BMP-Smad1/5 pathway in heart tissue. The specification is limited to a method of treating or preventing HFpEF in a subject by administering a FXI polypeptide mutant having the amino acid sequence of SEQ ID NO:43 or 44, monitoring their effectiveness in treating or preventing HFpEF, and activating the BMP-Smad1/5 pathway in heart tissue by overexpressing the FXI polypeptide mutant having the amino acid sequence of SEQ ID NO:43 or 44.
The quantity of experimentation required to practice the claimed invention based on the teachings of the specification.
While enzyme isolation techniques, recombinant and mutagenesis techniques were known in the art at the time of the invention, e.g. mutagenesis, and it is routine in the art to screen for variants comprising multiple substitutions or multiple modifications as encompassed by the instant claims, the specific amino acid positions within the protein's sequence where amino acid modifications can be made with a reasonable expectation of success in obtaining the desired activity/utility are limited in any protein and the result of such modifications is unpredictable. In addition, one skilled in the art would expect any tolerance to modification for a given protein to diminish with each further and additional modification, e.g. multiple substitutions.
In the absence of: (a) rational and predictable scheme for treating/preventing HFpEF in a subject and/or activating the BMP-Smad1/5 pathway in heart tissue with any FXI polypeptide comprising a functional catalytic domain or any polynucleotide encoding any FXI polypeptide comprising a functional catalytic domain and (b) a correlation between structure and the function of a FXI polypeptide/polynucleotide having the function of treating/preventing HFpEF in a subject and/or activating the BMP-Smad1/5 pathway in heart tissue, the specification provides insufficient guidance as to which of the essentially infinite possible choices is likely to be successful. One of skill in the art would have to test these infinite possible polypeptides to determine which FXI polypeptides/polynucleotides is able to treat/prevent HFpEF in a subject and/or activate the BMP-Smad1/5 pathway in heart tissue. While enablement is not precluded by the necessity for routine screening, if a large amount of screening is required, as is the case herein, the specification must provide a reasonable amount of guidance which respect to the direction in which the experimentation should proceed so that a reasonable number of species can be selected for testing. In view of the fact that such guidance has not been provided in the instant specification, it would require undue experimentation to enable the full scope of the claims.
The state of prior art, the relative skill of those in the art, and predictability or unpredictability of the art.
Zabczyk (Active tissue factor and activated factor XI in circulating blood of patients with systolic heart failure due to ischemic cardiomyopathy. Pol Arch Med Wewn. 2010 Sep;120(9):334-40– form PTO-1449) discloses that elevated clotting factors (FXI) and thrombin generation have been reported to occur in patients with heart failure (abstract). Loeffen (Factor XIa and Thrombin Generation Are Elevated in Patients with Acute Coronary Syndrome and Predict Recurrent Cardiovascular Events. PLoS One. 2016 Jul 15;11(7):e0158355 – form PTO-1449) discloses that ACS (acute coronary syndrome) patients had an enhanced prothrombotic profile, demonstrated by an increased thrombin generation potential, factor XIa and D-dimer levels. This study is the first to demonstrate the positive association between factor XIa, thrombin generation and recurrent cardiovascular events (abstract). A method of using FXI polypeptide or polynucleotide encoding FXI polypeptide to treat heart failure with preserved ejection fraction (HfpEF) or activate BMP-Smad1/5 pathway in heart tissue was not known in the prior art.
Since the amino acid sequence of the polypeptide/encoded polypeptide determines its structural and functional properties, predictability of which changes can be tolerated in a protein's amino acid sequence and obtain the desired activity requires a knowledge of and guidance with regard to which amino acids in the protein's sequence, if any, are tolerant of modification and which are conserved (i.e. expectedly intolerant to modification), and detailed knowledge of the ways in which the proteins' structure relates to its function. In the instant case, neither the specification or the art provide a correlation between structure and activity such that one of skill in the art can envision the structure of any FXI polypeptide comprising a functional catalytic domain having the function of treating/preventing HFpEF in a subject and/or activating the BMP-Smad1/5 pathway in heart tissue or predict said function of a polypeptide from its primary structure. In addition, the art does not provide any teaching or guidance as to (1) which amino acids within any FXI polypeptide that can be modified and which ones are conserved such that one of skill in the art can make and use the polypeptide to treating/preventing HFpEF in a subject and/or activating the BMP-Smad1/5 pathway in heart tissue, (2) which segments of any FXI polypeptide are essential for having the function of treating/preventing HFpEF in a subject and/or activating the BMP-Smad1/5 pathway in heart tissue, and (3) the general tolerance of any FXI polypeptide to structural modifications and the extent of such tolerance. The art clearly teaches that changes in a protein's amino acid sequence to obtain the desired activity without any guidance/knowledge as to which amino acids in a protein are required for that activity is highly unpredictable. At the time of the invention there was a high level of unpredictability associated with altering a polypeptide sequence with an expectation that the polypeptide will maintain the desired activity. For example, Studer (Residue mutations and their impact on protein structure and function: detecting beneficial and pathogenic changes. Biochem. J. (2013) 449, 581–594. – cited previously on form PTO-892) teach that (1) protein engineers are frequently surprised by the range of effects caused by single mutations that they hoped would change only one specific and simple property in enzymes, (2) the often surprising results obtained by experiments where single mutations are made reveal how little is known about the rules of protein stability, and (3) the difficulties in designing de novo stable proteins with specific functions.
Fransceus (J Ind Microbiol Biotechnol. 2017 May;44(4-5):687-695. – cited previously on form PTO-892) reviews protein engineering techniques, such as random mutagenesis and recombination, directed evolution and iterative or combinatory saturation “hotspots”. Fransceus states that “a recurring problem, however, is choosing which amino acid positions should be targeted. Answering this question is not an easy feat and requires substantial insight in the relationship between an enzyme’s sequence or structure and its properties.” Sanavia (Computational and Structural Biotechnology Journal, Volume 18, 2020, Pages 1968-1979. – cited previously on form PTO-892) discloses challenges in the prediction of protein stability in the occurrence of multiple mutations. “Multiple-point mutations are common variations of the protein sequence that may be needed in protein engineering when a single-point mutation is not enough to yield the desired stability change. Dealing with multiple-site variations adds another level of complexity beyond the prediction of the effect of a single variant on protein stability, since it requires the learning of many types of combinatorial effects”.
The amount of direction or guidance presented and the existence of working examples.
The specification is limited to a method of treating or preventing HFpEF in a subject by administering a FXI polypeptide mutant having the amino acid sequence of SEQ ID NO:43 or 44, monitoring their effectiveness in treating or preventing HFpEF, and activating the BMP-Smad1/5 pathway in heart tissue by overexpressing the FXI polypeptide mutant having the amino acid sequence of SEQ ID NO:43 or 44. However, the speciation fails to provide any information as to the structural elements required in a FXI polypeptide/polynucleotide having the function of treating/preventing HfpEF in a subject and/or activating the BMP-Smad1/5 pathway in heart tissue.
Thus, in view of the overly broad scope of the claims, the lack of guidance and working examples provided in the specification, the high level of unpredictability of the prior art in regard to structural changes and their effect on function and the lack of knowledge about a correlation between structure and function, an undue experimentation would be necessary one having ordinary skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims. The scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without sufficient guidance, determination of polypeptides having the desired biological characteristics recited in the claims are unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988).
Applicant's arguments filed August 4, 2026 have been fully considered but they are not persuasive.
Applicant argues that the specification sufficiently describes the claimed subject matter because (1) claims 1, 24, and 38 have been amended to recite a FXI polypeptide comprising a functional catalytic domain and (2) given the highly conserved nature of the Factor XI proteins, one having ordinary skill in the art would have been able to predictably identify members of this genus without undue experimentation, and (3) the specification provides exemplary FXI polypeptides comprising a functional catalytic domain, such as Example 9 and Table 7.
This is not found persuasive.
The instant claims are not product claims directed to FXI polypeptides or the exemplary FXI polypeptides. Instead, the claims are drawn to a method of using any FXI polypeptide having a functional catalytic domain having unknown structure or any polynucleotides encoding said FXI polypeptides having unknown structure to (1) treat or prevent HFpEF in a subject, (2) activate BMP-Smad1/5 pathway in heart tissue, and (3) monitoring the effectiveness of the administering of a composition said genus of FXI polypeptide or genus of polynucleotides. Example 9 and Table 7 of the instant specification are limited to an intact functional catalytic domain of two FXI polypeptides of SEQ ID NO:43 and 44 and two mutations sites that are necessary for having catalytic activity. The specification does not provide catalytic domains of any FXI polypeptides.
In the absence of: (a) rational and predictable scheme for treating/preventing HFpEF in a subject and/or activating the BMP-Smad1/5 pathway in heart tissue with any FXI polypeptide comprising a functional catalytic domain or any polynucleotide encoding any FXI polypeptide comprising a functional catalytic domain and (b) a correlation between structure and the function of a FXI polypeptide/polynucleotide having the function of treating/preventing HfpEF in a subject and/or activating the BMP-Smad1/5 pathway in heart tissue, the specification provides insufficient guidance as to which of the essentially infinite possible choices is likely to be successful. One of skill in the art would have to test these infinite possible polypeptides to determine which FXI polypeptides/polynucleotides is able to treat/prevent HfpEF in a subject and/or activate the BMP-Smad1/5 pathway in heart tissue. While enablement is not precluded by the necessity for routine screening, if a large amount of screening is required, as is the case herein, the specification must provide a reasonable amount of guidance which respect to the direction in which the experimentation should proceed so that a reasonable number of species can be selected for testing. In view of the fact that such guidance has not been provided in the instant specification, it would require undue experimentation to enable the full scope of the claims.
Hence the rejection is maintained.
Allowable Subject Matter
Claims 5-7 and 27-28 are 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
Claims 1, 5-8, 11, 13-14, 19, 21, 23-28, 31, 33-34, and 38-39 are pending.
Claims 1, 8, 11, 13-14, 19, 21, 23-26, 31, 33-34, and 38-39 are rejected.
Claims 5-7 and 27-28 are objected.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/YONG D PAK/Primary Examiner, Art Unit 1652
