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 .
Claim Interpretation
SEQ ID NO: 5 is a peptide consisting of the TAT cell penetrating peptide SEQ ID NO: 2 (GRKKRRQRRRPPQ) fused to the N-terminus of the NaKtide peptide SEQ ID NO: 1 (SATWLALSRIAGLCNRAVFQ): GRKKRRQRRRPPQSATWLALSRIAGLCNRAVFQ.
SEQ ID NO: 5 is also named pNaKtide, as evidenced by paras. [0004] and [0050] of the specification.
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.
Issues Relevant to Both Written Description and Enablement Presented Once for Brevity
Nature of the Invention/Scope of the Claims
Claims 1-10 are drawn to methods for treating anemia. Claims 11-19 are drawn to methods of increasing the half-life of red blood cells. Both sets of claims use a polypeptide antagonist of a Na/K ATPase/Src receptor complex having the sequence of SEQ ID NO: 1, or a functional fragment and/or variant thereof, further including a cell penetrating peptide.
A “fragment” is defined at [0045] and a “variant” is defined at [0046]. The definitions permit substitution, addition, and deletion at every amino acid position in SEQ ID NO: 1 as well as fragmentation. However, only those sequences meeting the structural and functional requirements of the genus are encompassed by the claim. Therefore, claims 1, 3-11, 13-17, and 19 encompass all variants and/or fragments of SEQ ID NO: 1 that are able to antagonize a Na/K ATPase/Src receptor complex sufficient to treat anemia and/or increase the half-life of red blood cells.
Claims 2, 12, and 18 are limited to polypeptides comprising full-length SEQ ID NO: 5.
In claims 1-10, the subject is limited to those identified as having anemia characterized by a reduced number of red blood cells. In claims 11-16, the subject is limited to those in need of an increase in red blood cell half-life. In claims 17-19, the subject is limited to those having red blood cells.
Actual reduction to practice/Working examples
The instant specification includes a limited reduction to practice: the only polypeptide antagonist reduced to practice is SEQ ID NO: 5.
Guidance in the specification/Structure-function correlation
The specification does not describe a general correlation between structure and function for the claimed genus. The role of each of the amino acids of SEQ ID NO: 1 on the ability of the polypeptide to antagonize a Na/K ATPase/Src receptor complex sufficient to treat anemia and/or increase the half-life of red blood cells are not described. As a result, it is impossible to predict, based on the specification, how changing any position will affect the claimed function.
State of the Prior Art/Level of Skill in the Art/Predictability
The prior art discloses, like the reduction to practice in the specification, the use of SEQ ID NO: 5 to treat anemia in subjects with chronic kidney disease. The prior art does not reduce to practice the use of variants and/or fragments thereof. See Liu et al., Xie et al., and Chaudry et al. in the anticipation rejections below. There is a high degree of unpredictability in the prior art with respect to peptide structure-function. The specification acknowledges at [0046] that some amino acid changes result in a significant change in function, whereas others result in little or no change. The specification also acknowledges the complexity of anemia associated with chronic kidney disease [0004].
Claims 1, 3-11, 13-17, and 19 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.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
Only SEQ ID NO: 5 was reduced to practice for treating subjects with anemia associated with kidney disease or in need of increased red blood cell half-life. As discussed above the claim scope is enormous given the breadth of structural limitations and complexity of functional limitations in the claims. Therefore, one of ordinary skill in the art would not consider SEQ ID NO: 5, which comprises an antagonist identical to SEQ ID NO: 1 and a cell-penetrating peptide to be representative of the full scope of the claimed genus, which includes all functional variants and/or fragments.
The data presented in the specification raise more questions about the physical properties of the genus than they answer. The data do not suggest the physical basis for the claimed activity and therefore do not describe which substitutions, deletions or additions could be made while preserving function. Understanding the physical basis for the claimed activity is critical to determining which of the sequences that meet the structural requirements of the genus also meet the functional requirements of the genus.
The specification does not describe a general correlation between structure and function for the claimed genus. The role of the 20 amino acids of SEQ ID NO: 1 in the ability to antagonize a Na/K ATPase/Src receptor complex sufficient to treat anemia and/or increase the half-life of red blood cells are not described. As a result, it is impossible to predict, based on the specification, how changing any position will affect the claimed functions.
Given the level of unpredictability in the peptide art, one of ordinary skill in the art would not know which of the countless peptides that meet the structural requirements of the claims would also be able to perform the complicated claimed functions. The specification does not make clear which peptides are in the genus and which are not because it does not describe the physical basis for the claimed activity. In other words, the specification does not describe which peptides to make.
For these reasons, the skilled artisan would not reasonably conclude that the inventor(s), at the time the application was filed, had possession of the full scope of the claimed invention. In conclusion, only methods involving administration of SEQ ID NO: 5 meet the written description provision of 35 U.S.C. 112(a).
Claims 1, 3-11, 13-17, and 19 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 using SEQ ID NO: 5 in the claimed methods does not reasonably provide enablement for the use of any other polypeptide having the ability to antagonize a Na/K ATPase/Src receptor complex sufficient to treat anemia and/or increase the half-life of red blood cells. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
To comply with the enablement requirements of 35 U.S.C. §112, first paragraph, a specification must adequately teach how to make and how to use a claimed invention throughout its scope, without undue experimentation. Plant Genetic Systems N.V. v. DeKalb Genetics Corp., 315 F.3d 1335, 1339, 65 USPQ2d 1452, 1455 (Fed. Cir. 2003). There are a variety of factors which may be considered in determining whether a disclosure would require undue experimentation. These factors 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. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
Factors (2)-(8) are discussed above.
The scope of the claimed compositions is extremely broad relative to the narrow reduction to practice in the specification. That fact combined with the level of unpredictability and complexity in the art, the relative skill in the art, and the lack of specific guidance in the specification, poses an undue burden of experimentation on one of ordinary skill in the art seeking to practice the claimed methods. The specification is an invitation to undertake a research program to identify additional compositions that could be used to carry out different embodiments of the claims. As such, the specification fails to meet the enablement provision of 35 U.S.C. 112(a).
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-3, 5-10, and 17-19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Liu et al. (Attenuation of Na/K-ATPase Mediated Oxidant Amplification with pNaKtide Ameliorates Experimental Uremic Cardiomyopathy. Sci Rep 6, 34592 (2016)).
Liu et al. teach that pNaKtide substantially alleviates PNx-induced anemia in a mouse model of experimental renal failure (Fig. 2A). Liu et al. teach that pNaKtide reverses anemia (Fig. 4A).
Liu et al. teach that anemia in patients with chronic kidney disease is associated with poor outcome, increased cardiovascular disease and mortality, and that pNaKtide ameliorates anemia associated with chronic renal failure (p. 4, para. 3).
Liu et al. teaches all of the limitations of instant claim 1:
Claim 1
Liu et al.
Analysis
A method for treating anemia comprising
Liu et al. teach that pNaKtide substantially alleviates PNx-induced anemia in a mouse model of experimental renal failure (Fig. 2A). Liu et al. teach that pNaKtide reverses anemia (Fig. 4A). Liu et al. teach that anemia in patients with chronic kidney disease is associated with poor outcome, increased cardiovascular disease and mortality, and that pNaKtide ameliorates anemia associated with chronic renal failure (p. 4, para. 3).
The method disclosed by Liu et al. treats anemia in the subjects.
identifying a subject as having anemia characterized by a reduced number of red blood cells
Liu et al. teach measuring the hematocrit (HCT (%)) of subjects (Fig. 2A). Subjects with a significant decrease in hematocrit were characterized as being anemic (see legend of Fig. 2A).
Hematocrit is the percentage of blood volume that is occupied by red blood cells or erythrocytes, as evidenced by the definition in para. [0043] of the specification. Therefore, a step of identifying a subject with a reduced hematocrit, is a step of identifying a subject as having anemia characterized by a reduced number of red blood cells.
administering a polypeptide antagonist of a Na/K ATPase/Src receptor complex to the subject, the polypeptide antagonist having the sequence of SEQ ID NO: 1, or a functional fragment, and/or functional variant thereof, and the polypeptide antagonist further including a cell penetrating peptide
Liu et al. teach administering pNaKtide to the subjects with anemia (i.e. having a reduced hematocrit).
As evidenced by the specification at para. [0050], pNaKtide is a peptide identical to instant SEQ ID NO: 5, which consists of the cell-penetrating peptide SEQ ID NO: 2 fused to the N-terminus of SEQ ID NO: 1.
Therefore, Liu et al. anticipates instant claim 1.
With respect to claim 2, Liu et al. teach pNaKtide, which is identical to instant SEQ ID NO: 5, as evidenced by the specification para. [0050].
With respect to claim 3, Liu et al. teach pNaKtide, which contains the cell-penetrating peptide TAT identical to instant SEQ ID NO: 2, as evidenced by the specification para. [0050].
With respect to claim 5, Liu et al. teach that pNaKtide increases a hematocrit level in a subject (Fig. 2A, Fig. 4A).
With respect to claims 6-8, Liu et al. are silent regarding the effect of pNaKtide on the amount of reticulocytes, red blood cell half-life, and amount of eryptosis in the subject. Given that Liu et al. teach administering the same compound (pNaKtide) to the same subjects (anemic with chronic kidney disease), the prior art method inherently meets these functional limitations.
With respect to claims 9-10, Liu et al. teach that anemia in patients with chronic kidney disease is associated with poor outcome, increased cardiovascular disease and mortality, and that pNaKtide ameliorates anemia associated with chronic renal failure (p. 4, para. 3).
With respect to claims 17-19, the method of administration taught by Liu et al. inherently involves contacting a red blood cell of the subject with pNaKtide. Given that Liu et al. teach administering the same compound (pNaKtide) to the same subjects (anemic with chronic kidney disease, having red blood cells), the prior art method inherently meets the functional limitation “increasing red blood cell half-life”.
Claims 11-13 and 15-16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Liu et al. (Attenuation of Na/K-ATPase Mediated Oxidant Amplification with pNaKtide Ameliorates Experimental Uremic Cardiomyopathy. Sci Rep 6, 34592 (2016)), as applied to claims 1-3, 5-10, and 17-19 above, as evidenced by Li et al. (Red Blood Cell Lifespan Shortening in Patients with Early-Stage Chronic Kidney Disease. Kidney Blood Press Res (2019) 44 (5): 1158–1165).
MPEP § 2131.01(III) states: A rejection under 35 U.S.C. 102 over multiple references is proper when the extra reference or other evidence can be used to show an inherent characteristic of the thing in the primary reference. "To serve as an anticipation when the reference is silent about the asserted inherent characteristic, such gap in the reference may be filled with recourse to extrinsic evidence. Such evidence must make clear that the missing descriptive matter is necessarily present in the thing described in the reference, and that it would be so recognized by persons of ordinary skill." Continental Can Co. USA v. Monsanto Co., 948 F.2d 1264, 1268, 20 USPQ2d 1746, 1749-50 (Fed. Cir. 1991). The critical date of extrinsic evidence showing a universal fact need not antedate the filing date. See MPEP § 2124.
In the instant case, Liu et al. are silent with respect to the half-life of red blood cells in the disclosed subjects. Li et al. provide evidence that reduced red blood cell (RBC) lifespan shortening is a primary correlate of renal anemia at all stages of chronic kidney disease, present at early-stage and end-stage (abstract). Therefore, the subjects taught by Liu et al., which are an animal model for chronic kidney disease, inherently possesses the characteristic “in need of increasing red blood cell half-life” as required by claims 11-13 and 15-16. These claims are rejected for the same reasons as presented above.
Claims 1-10 and 17-19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Xie et al. (US 2020/0085918 A1).
Xie et al. teach methods for treating anemia that comprise administering a polypeptide antagonist of a Na/K ATPase/Src receptor complex to a subject in need thereof ([0016]). The polypeptides are at least 75% identical to the pNaKtide polypeptide of SEQ ID NO: 1 ([0056]), which is identical to instant SEQ ID NO: 1. The polypeptides further comprises a cell penetrating peptide (CPP) ([0054]). The CPPs include the trans-activating transcriptional activator (TAT) cell penetrating peptide (SEQ ID NO: 2), penetratin (SEQ ID NO: 3), and the N-terminal poly-lysine domain of the α1 subunit of Na/K-ATPase (SEQ ID NO: 4) ([0055]), which are identical to instant SEQ ID NOs: 2-4. Xie et al. teach pNaKtide (e.g., SEQ ID NO: 5; GRKKRRQRRRPPQSATWLALSRIAGLCNRAVFQ, which includes the TAT cell penetrating peptide of SEQ ID NO: 2 fused to the NaKtide sequence of SEQ ID NO: 1) ([0055]), which is identical to instant SEQ ID NO: 5.
Xie et al teach methods of treating profound anemia, which is generally present in chronic kidney failure, and treatment of uremic cardiomyopathy characterized by a decrease in profound anemia ([0066]). Xie et al. demonstrate that treatments with pNaKtide increased the hematocrit in a dose-dependent manner, and profound anemia caused by nephrectomy was substantially alleviated ([0066], [0076]).
Xie et al. teach that anemia refers to an absolute reduction of the total number of circulating red blood cells (RBCs), and is considered when one or more of the following are decreased: hemoglobin, hematocrit, or red blood cell (RBC) count. Hematocrit is the percentage of the blood volume that is occupied by red blood cells or erythrocytes ([0067]).
Xie et al. teach in Fig. 3A that pNaKtide increases hematocrit levels in PNx mice. PNx induced profound anemia which was substantially alleviated by concomitant administration of pNaKtide (FIG. 3A) ([0091]). PNx induced profound anemia was substantially alleviated by administration of higher doses of pNaKtide (FIG. 8B) ([0096]). Data showed that amelioration of the anemia associated with chronic renal failure was noted with pNaKtide ([0098]). One week of pNaKtide administration significantly improved established anemia in our model of experimental renal failure ([0099]).
Xie et al. teaches all of the limitations of instant claim 1:
Claim 1
Xie et al.
Analysis
A method for treating anemia comprising
Xie et al. teach in Fig. 3A that pNaKtide increases hematocrit levels in PNx mice. PNx induced profound anemia which was substantially alleviated by concomitant administration of pNaKtide (FIG. 3A) ([0091]). PNx induced profound anemia was substantially alleviated by administration of higher doses of pNaKtide (FIG. 8B) ([0096]). Data showed that amelioration of the anemia associated with chronic renal failure was noted with pNaKtide ([0098]). One week of pNaKtide administration significantly improved established anemia in our model of experimental renal failure ([0099]).
The method disclosed by Liu et al. treats anemia in the subjects.
identifying a subject as having anemia characterized by a reduced number of red blood cells
Xie et al. teach measuring the hematocrit (HCT (%)) of subjects (Fig. 3A). Subjects with a significant decrease in hematocrit were characterized as being anemic (see Example 2).
Hematocrit is the percentage of blood volume that is occupied by red blood cells or erythrocytes, as evidenced by the definition in para. [0043] of the specification. Therefore, a step of identifying a subject with a reduced hematocrit, is a step of identifying a subject as having anemia characterized by a reduced number of red blood cells.
administering a polypeptide antagonist of a Na/K ATPase/Src receptor complex to the subject, the polypeptide antagonist having the sequence of SEQ ID NO: 1, or a functional fragment, and/or functional variant thereof, and the polypeptide antagonist further including a cell penetrating peptide
Xie et al. teach administering pNaKtide to the subjects with anemia (i.e. having a reduced hematocrit).
Xie et al. teach pNaKtide (e.g., SEQ ID NO: 5; GRKKRRQRRRPPQSATWLALSRIAGLCNRAVFQ, which includes the TAT cell penetrating peptide of SEQ ID NO: 2 fused to the NaKtide sequence of SEQ ID NO: 1) ([0055]), which is identical to instant SEQ ID NO: 5.
pNaKtide is a peptide identical to instant SEQ ID NO: 5, which consists of the cell-penetrating peptide SEQ ID NO: 2 fused to the N-terminus of SEQ ID NO: 1.
Therefore, Xie et al. anticipates instant claim 1.
With respect to claim 2, Xie et al. teach pNaKtide, which is identical to instant SEQ ID NO: 5, as evidenced by [0055].
With respect to claim 3, Xie et al. teach pNaKtide, which contains the cell-penetrating peptide TAT identical to instant SEQ ID NO: 2, as evidenced by [0055]. Xie et al. also teach SEQ ID NOs: 3-4 ([0055]).
With respect to claim 4, Xie et al. teach that pNaKtide can be administered by oral administration, transdermal administration, administration by inhalation, nasal administration, topical administration, intraaural administration, rectal administration, intravenous administration, intramuscular administration, subcutaneous administration, intravitreous administration, subconjunctival administration, intracameral administration, intraocular administration or combinations thereof ([0012], [0071]).
With respect to claim 5, Xie et al. teach that pNaKtide increases a hematocrit level in a subject (Fig. 3A, Fig. 8A).
With respect to claims 6-8, Xie et al. are silent regarding the effect of pNaKtide on the amount of reticulocytes, red blood cell half-life, and amount of eryptosis in the subject. Given that Xie et al. teach administering the same compound (pNaKtide) to the same subjects (anemic with chronic kidney failure), the prior art method inherently meets these functional limitations.
With respect to claims 9-10, Xie et al teach methods of treating profound anemia, which is generally present in chronic kidney failure ([0066]).
With respect to claims 17-19, the method of administration taught by Xie et al. inherently involves contacting a red blood cell of the subject with pNaKtide. Given that Xie et al. teach administering the same compound (pNaKtide) to the same subjects (anemic with chronic kidney failure, having red blood cells), the prior art method inherently meets the functional limitation “increasing red blood cell half-life”.
Claims 11-16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Xie et al. (US 2020/0085918 A1), as applied to claims 1-10, and 17-19 above, as evidenced by Li et al. (Red Blood Cell Lifespan Shortening in Patients with Early-Stage Chronic Kidney Disease. Kidney Blood Press Res (2019) 44 (5): 1158–1165).
MPEP § 2131.01(III) states: A rejection under 35 U.S.C. 102 over multiple references is proper when the extra reference or other evidence can be used to show an inherent characteristic of the thing in the primary reference. "To serve as an anticipation when the reference is silent about the asserted inherent characteristic, such gap in the reference may be filled with recourse to extrinsic evidence. Such evidence must make clear that the missing descriptive matter is necessarily present in the thing described in the reference, and that it would be so recognized by persons of ordinary skill." Continental Can Co. USA v. Monsanto Co., 948 F.2d 1264, 1268, 20 USPQ2d 1746, 1749-50 (Fed. Cir. 1991). The critical date of extrinsic evidence showing a universal fact need not antedate the filing date. See MPEP § 2124.
In the instant case, Xie et al. are silent with respect to the half-life of red blood cells in the disclosed subjects. Li et al. provide evidence that reduced red blood cell (RBC) lifespan shortening is a primary correlate of renal anemia at all stages of chronic kidney disease, present at early-stage and end-stage (abstract). Therefore, the subjects taught by Xie et al., which have chronic kidney disease, inherently possesses the characteristic “in need of increasing red blood cell half-life” as required by claims 11-16. These claims are rejected for the same reasons as presented above.
Claims 11-13 and 15-19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chaudhry et al. (Effects of pNaKtide in 5/6 Partial Nephrectomy mouse model having benefits on Red Blood Cells survival and Cardiac Function. Proceedings of the West Virginia Academy of Science, (2020) 92(1), published April 29, 2020).
Chaudry et al. teach a method of increasing half-life of red blood cells comprising administering pNaKtide to a subject that is an experimental CKF 5/6 partial nephrectomy (PNx)mouse model (abstract). Chaudry et al. teach that the pNaKtide administration results in a statistically-significant increase in red blood cell half-life (abstract). As noted above, pNaKtide is identical to instant SEQ ID NO: 5 and consists of instant SEQ ID NO: 2 fused to instant SEQ ID NO: 1.
Therefore, Chaudry et al. satisfy all of the limitations of and anticipate instant claims 11-13 and 17-19.
With respect to claims 15-16, Chaudry et al. are silent regarding the effect of pNaKtide on the amount of reticulocytes, and amount of eryptosis in the subject. Given that Chaudry et al. teach administering the same compound (pNaKtide) to the same subjects (chronic renal failure), the prior art method inherently meets these functional limitations.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 4 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al., as applied to claims 1-3, 5-13, and 15-19 above, in further view of Xie et al. (US 2020/0085918 A1).
Liu et al. teach that pNaKtide is administered by intraperitoneal injection (p. 8), which is not recited in claims 4 or 14.
Xie et al. teach that pNaKtide can be administered by oral administration, transdermal administration, administration by inhalation, nasal administration, topical administration, intraaural administration, rectal administration, intravenous administration, intramuscular administration, subcutaneous administration, intravitreous administration, subconjunctival administration, intracameral administration, intraocular administration or combinations thereof (para. [0012], [0071]).
It would have been obvious to one of ordinary skill in the art at the time the application was filed to use any of the administration routes taught by Xie et al. for pNaKtide administration in the method taught by Liu et al. It is within the ordinary skill of the art to optimize the administration route of a drug. Xie et al. provide a reasonable expectation of success by teaching that many routes are suitable for pNaKtide.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Chaudry et al., as applied to claims 11-13 and 15-19 above, in further view of Xie et al. (US 2020/0085918 A1).
Chaudry et al. do not teach the administration route.
Xie et al. teach that pNaKtide can be administered by oral administration, transdermal administration, administration by inhalation, nasal administration, topical administration, intraaural administration, rectal administration, intravenous administration, intramuscular administration, subcutaneous administration, intravitreous administration, subconjunctival administration, intracameral administration, intraocular administration or combinations thereof (para. [0012], [0071]).
It would have been obvious to one of ordinary skill in the art at the time the application was filed to use any of the administration routes taught by Xie et al. for pNaKtide administration in the method taught by Chaudry et al. It is within the ordinary skill of the art to optimize the administration route of a drug. Xie et al. provide a reasonable expectation of success by teaching that many routes are suitable for pNaKtide.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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Claims 1-10 and 17-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 11,865,162 B2. Although the claims at issue are not identical, they are not patentably distinct from each other.
Patented claim 4 recites a method for treating anemia, comprising administering a polypeptide antagonist of a Na/K ATPase/Src receptor complex to a subject in need thereof, wherein the polypeptide antagonist comprises the sequence of SEQ ID NO: 1 or a functional fragment thereof, and wherein the anemia is chronic kidney disease-induced anemia, wherein the polypeptide antagonist further includes a cell penetrating polypeptide encoded by an amino acid sequence selected from the group consisting of SEQ ID NOS: 2-4.
The patented claims do not require a step of identifying a subject having anemia characterized by a reduced number of red blood cells.
It would have been obvious to include a step of identifying anemic patients in order to meet the claim limitation “subject in need thereof”. Anemia is defined as an absolute reduction of the total number of circulating red blood cells (RBCs), and is considered when one or more of the following are decreased: hemoglobin, hematocrit, or red blood cell (RBC) count. Hematocrit is the percentage of the blood volume that is occupied by red blood cells or erythrocytes (patent disclosure col 10, lines 39-44). Therefore, identifying a subject in need thereof, as required by the claim, involves identifying a subject with a reduction in the total number of circulating red blood cells, thereby satisfying all of the limitations of instant claims 1, 3, 9, and 10.
With respect to claim 2, the patent claims require SEQ ID NO: 1 and SEQ ID NO:2, which are the component parts of SEQ ID NO: 5.
Regarding claim 4, patented claim 5 requires that the administering step includes oral administration, transdermal administration, administration by inhalation, nasal administration, topical administration, intraaural administration, rectal administration, intravenous administration, intramuscular administration, subcutaneous administration, intravitreous administration, subconjunctival administration, intracameral administration, intraocular administration or combinations thereof.
Regarding claim 5, patented claim 2 requires that administering the polypeptide antagonist comprises administering an amount of the polypeptide antagonist sufficient to increase an amount of hematocrit in the subject.
With respect to claims 6-8, the patented claims are silent regarding the effect on the amount of reticulocytes, red blood cell half-life, and amount of eryptosis in the subject. Given that the patented claims require administering the same compound to the same subjects, they inherently meets these functional limitations.
With respect to claims 17-19, the method of administration recited in the patented claims inherently involves contacting a red blood cell of the subject. Given that the patented claims require administering the same compound to the same subjects, they inherently meets the functional limitation “increasing red blood cell half-life”.
Claims 11-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 11,865,162 B2, as applied to claims 1-10 and 17-19 above, as evidenced by Li et al. (Red Blood Cell Lifespan Shortening in Patients with Early-Stage Chronic Kidney Disease. Kidney Blood Press Res (2019) 44 (5): 1158–1165). Although the claims at issue are not identical, they are not patentably distinct from each other.
MPEP § 2131.01(III) states: A rejection under 35 U.S.C. 102 over multiple references is proper when the extra reference or other evidence can be used to show an inherent characteristic of the thing in the primary reference. "To serve as an anticipation when the reference is silent about the asserted inherent characteristic, such gap in the reference may be filled with recourse to extrinsic evidence. Such evidence must make clear that the missing descriptive matter is necessarily present in the thing described in the reference, and that it would be so recognized by persons of ordinary skill." Continental Can Co. USA v. Monsanto Co., 948 F.2d 1264, 1268, 20 USPQ2d 1746, 1749-50 (Fed. Cir. 1991). The critical date of extrinsic evidence showing a universal fact need not antedate the filing date. See MPEP § 2124.
In the instant case, the patented claims are silent with respect to the half-life of red blood cells in the disclosed subjects. Li et al. provide evidence that reduced red blood cell (RBC) lifespan shortening is a primary correlate of renal anemia at all stages of chronic kidney disease, present at early-stage and end-stage (abstract). Therefore, the subjects recited in the patented methods, which have chronic kidney disease, inherently possesses the characteristic “in need of increasing red blood cell half-life” as required by claims 11-16. These claims are rejected for the same reasons as presented above.
Conclusion
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/CHRISTINA BRADLEY/Primary Examiner, Art Unit 1654
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