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 Rejections 35 USC 112(A)
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, 2, 8-15, 19, 21, 26, 29, 32, 33, 35, 44, 49 and 50 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 § 2137 states that "the written description requirement for a genus must be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, 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 (see i)(C), above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
For written description, the analysis (a) considers actual reduction to practice, (b) disclosure of drawing or structural chemical formulas, (c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties, functional characteristics when coupled with known or disclosed and (d) representative number of examples.
The claims are drawn to any modified Serp-1 protein or fragment, comprising at least one therapeutic enhancing moiety, wherein the protein is biologically active and stable at a temperature of 25⁰C (standardized room temperature) or more.
actual reduction to practice/(b) disclosure of drawing or structural chemical formulas:
This application has only reduced to practice 8 modified Serp-1 full length proteins with PEG as the therapeutically enhancing moiety (Fig. 3). The examples of the specification only show making modSerp-1m5, m10, m20, m30 and m40, which is the full length Serp-1 protein modified with 5-40K PEG conjugates at multiple lysine sites (see fig. 3) and modSerp-1s10, s20, s30, and s40, which are single N-terminal 10-40k PEG conjugates of the full length Serp-1 protein (Fig. 3-4). Only PEGSerp-1m5 was reduced to practice as an example to show the Serp-1 conjugates have thermal stability above 25⁰C (Fig. 5). Furthermore, only the full length wild-types Serp-1 sequence from myxoma virus was provided as SEQ ID NO: 1. Although the wild-type Serp-1 showed less thermal stability at temperatures over 55⁰C than modserp-1m5, thermal stability was only tested for one Serp-1 peptide with one therapeutic enhancing moiety, and only at temperatures up to 95⁰C, which does not represent the full scope of Serp-1 proteins with at least one therapeutically enhancing moiety being biologically active and stable at any temperature above 25⁰C.
(c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties
Regarding the limitation “biologically active,” the art teaches that RCL loop structural features are known to be needed for some biological activities and stability, according to Dai et al. ( The Journal of Biological Chemistry, Vol. 281, No. 12, 2006; abstract). However, the specification does not disclose any of the fragment examples, as discussed above, nor does the specification discuss what regions of the full length 369 residue protein are required for it to be biologically active. The specification only states that “some characteristic Serpin features including, but not limited to, an Aß sheet and a reactive center loop (RCL) may act as a bait and trap for target proteases,” but it does not provide any sequences of RCL loop fragments or any thermally stable examples of therapeutic enhancing moieties, other than the full length Serp-1 with PEG. This fails to provide adequate support for the relationship between the fragment structure and function claimed.
Regarding stability, there is also no discussion in the specification of what fragments of the 369 residue protein would have stability over 25⁰C room temperature, and no examples of what Serp-1 proteins or fragments that would be functional at temperatures over 95⁰C, as the modSerp-1m5 bands become much fainter around 65⁰C, which can be seen in the immunoblot assay example disclosed (Fig. 5). Additionally, PEG5K conjugation at lysine is only one species of therapeutic enhancing moiety at one conjugation site that is shown to have the stability at temperatures greater than 25⁰C. This does not provide sufficient structure/function relationship for any Serp-1 fragment, with any therapeutically enhancing moiety, at any temperature over 25⁰C, as Serpin-1 is known in the art to destabilize at around 60⁰C (Dai et al., p. 8044, Col. 1, para. 3).
Furthermore, is known in the art that RCL loops of the prototypical serpin molecule consist of 20–27 amino acids near the C terminus, but the art recognizes that protease inhibiting and anti-inflammatory activity are dependent upon the individual serpin protein, and the serine proteinase target (See Dai et al., abstract, p. 8041, spanning Col. 1-2). This art-recognized unpredictability of structure-function provides further evidence that the claimed scope of biological activity and thermal stability are not support by the disclosures of the specification, as it does not provide a required common core sequence for Serp-1 fragments with any therapeutic enhancing moiety having this relationship.
(d) Representative number of examples
A "representative number of species" means that the species which are adequately described are representative of the entire 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. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004)("[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated."). One example of a PEG 5K modified full length Serp-1 having enhanced stability over 25⁰C and 8 examples of PEG modified Serp-1 with biological activity does not represent the countless species of therapeutic enhancing moieties that could be used to modify the protein and its many species of fragments. that are encompassed by the claims. Given this lack of description in the specification, the application fails to describe the claimed invention in such a full, clear, and concise and exact terms that a skilled artisan would recognize that applicants were in possession of the genus of claimed invention.
Claim Rejections 35 USC 102(A)(1)
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.
Claim(s) 1, 2, 8-11, 13-15, 19, 21, 26, 29, 32, 33, 35, 44, 49 and 50 are rejected under 35 U.S.C. 102(A)(1) as being anticipated by Lucas et al. (WO2019/113258A1; See ISR) as evidenced by Dai et al. (The Journal of Biological Chemistry, Vol. 281, No. 12, 2006).
Lucas teaches the Serp-1 protein and Serp-1 RCL peptide fragments that consists of an area on the Serp-1 fragment protein from residues 305 -331, where the Sepr-1 protein sequence is:
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204
634
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(p. 33).
This reference teaches an isolated polypeptide comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of Myxoma virus Serine Proteinase Inhibitor 1 (Serp-1) as provided in SEQ ID NO: 1, wherein the amino acid sequence of the recombinant protein comprises one or more mutations at position L316, I317, or L316 and 1317 (claim 1, p. 37). Lucas teaches that various Serp-1 peptides were modified with stabilizing amino acid substitutions and that synthetic peptides include those with modified amino acids or other moieties in place of an amino acid to stabilize the peptide, block metabolization, or to create a conformational change in the peptide which would increase its effectiveness (p. 8, lines 15-25). In specific embodiments reduced to practice, Lucas teaches that the positions of residues associated with S-7 in Serp-1 are shown to form a ẞ-strand at the core of the protein, and appear predominantly stabilized by main-chain hydrogen bonding, and that the following mutations showed greater stability:
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152
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(Table 3). Lucas teaches that Negatively charged residue substitutions, Glu and Asp (pKa of 4.07 and 3.86, respectively), were favorable in order to increase the likelihood to form stabilizing hydrogen bonds with either adjacent residues or 25 solvent at physiological pH and the resultant peptides that displayed the highest favorable binding to human serpins were: MPS7-8 (G305TTASSDTAITLEPR319) (SEQ ID NO: 2), containing a single Ile to Glu substitution, and MPS7-9 (G305 TTASSDTAITDEPR319) (SEQ ID NO: 3), which has two substitutions of Ile to Glu and Leu to Asp (FIG. 1; p. 30, lines 21-29).
This reference also teaches that polyethylene glycol 15 (PEG)4000 was attached to Serp-1 to induce crystallization and promote Serp-1 packing (p. 22, lines 3-13; Fig. 9). Additionally, Lucas teaches a multitude of proteins conjugated to the S-7 position of RCL in table 5, including human serum albumin (p. 23-29). This reference also teaches that an isolated Serp-1 variant can be modified at the amino terminus, the carboxy terminus, or both (p. 9, lines 6-19). For example, Lucas teaches that an amino acid sequence encoding an RCL peptide variant may include at least two cysteine residues, one or both of which are at the C-terminal or N-terminal of the 10RCL peptide variant or the naturally occurring sequence (p. 9 lines 6-14). This reference also teaches that Serp-1 and RCL fragment sequences can be cyclized by a disulfide bond between these two cysteine residues and that cyclic peptides generally have an advantage over linear peptides in that their cyclic structure is more rigid, providing biological activity that may be higher than that of the corresponding linear peptide (p. 9, lines 14-17).
This reference further teaches that Serp-1 or RCL peptide variants can also include another substituent(moiety) at the amino-terminus or carboxy-terminus (p. 9, lines 6-10). Lucas teaches that such substituents can be an acyl group or a substituted or unsubstituted amine group For example, this reference teaches that in one embodiment, the N-terminus can be modified with an acyl group and the C-terminus can be amidated with an amine group substituted with a lower alkyl (p. 9, lines 19-25).
This meets the limitations of claim 1 because the peptide variants of Lucas are biologically active, and the specification states [para. 0046] that “In some embodiments, the therapeutic enhancing moiety comprises one, two, three, four or more amino acid substitutions, insertions, or deletions, wherein the substitutions are with natural or non-naturally encoded amino acids.” Furthermore, Lucas also teaches PEGylated Serp-1.
As to the stability at 25⁰C, this reference is silent on thermal stability; however, this property is inherent to the claimed composition, as the prior art teaches the exact compound(s) claimed. MPEP 2112 states: "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004), the court held that the claimed promoter sequence obtained by sequencing a prior art plasmid that was not previously sequenced was anticipated by the prior art plasmid which necessarily possessed the same DNA sequence as the claimed oligonucleotides. The court stated that "just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel." Id.
As such, the limitations of a modified Serp-1 protein being biologically active and stable at a temperature of 25°C room temperature is met by the substituted and PEG conjugated Serp-1 compositions of Lucas because they meet all of the structural limitations claimed. Furthermore, this example in Lucas was conducted at room temperature, or 25⁰C. In addition, Dai provides evidence to support stability at the claimed temperature, as this reference teaches that when Serp-1 was assessed for thermal stability, it precipitated with loss of activity at temperatures greater than 60 °C, demonstrating that altered activity was not indicative of a latent state in which proteins are stable at higher temperatures. (p. 8044, Col. 1, para. 4). As such, this reference provides further evidence that Serp-1 is stable up until 60⁰C, which covers stability at temperatures in the range of being above 25⁰C (room temperature).
Based on the biologically active Serp-1 proteins taught by Lucas, the above MPEP inherency standards and what is evidenced in the art, the limitations of claim 1 are met.
Claim 2 is met because Lucas teaches Serp-1 having at least 80% sequence identity to SEQ ID NO: 1 and biologically active fragments thereof (e.g., SEQ ID NOs: 2-4). Claims 8-11, 13 and 15 are met because Lucas teaches PEG4000, which is a water-soluble polymer within the range of 57 to 100,000 Da and unbranched. Claim 14 is met because Lucas teaches an acyl and alkyl group on the termini. As to claims 19 and 21, these are met because Lucas teaches that Serp-1 or Serp-1 derived peptide fragments can be modified with cysteine and at or near either terminus. Claims 26 and 29 are met because Lucas teaches covalent stabilizing amino acid substitutions, cysteine disulfide linkers, as well as a PEG linkage, and the specification [00124-00125] states that linkers may be “a group or bond formed as a result of a chemical reaction, and include a covalent linkage.” Claims 32, 33 and 35 are met because Lucas teaches that the recombinant Serp-1 was expressed and harvested from Chinese Hamster Ovarian (CHO) cell line, which is eukaryotic (p. 16, lines 25-28). Claim 44 is met because Lucas discloses half-life enhancing fusion peptides, such as HSA (spanning p. 9-10), and the exact time of the half-life is inherent to the composition itself, as the unmodified Serp-1 would not be changed by any substitutions, additional moieties, etc. that are well known to increase half-life. Therefore, the naturally occurring/unmodified peptide would have the inherent half-life of at least one hour. Thus, any modification to increase half-life meets the limitations of this property, absent evidence to the contrary. Specifically, Table 5 shows that the first protein bound to the S-7 position and tested was human serum albumin, which Lucas teaches is half-life enhancing (p. 23). Similarly, the exact time of stability at room temperature of over one minute, as recited in claim 49 is met, as it is inherent, as discussed above in MPEP 2112 and as evidenced by Dai, because the thermal stability would have to be as long as it took to run standard assay experiments, which would take longer than one minute, and Dai teaches that Serp-1 peptides was stable at a variety of temperatures, up to 60⁰C (p. 8044, Col. 1). Claim 50 is met because Lucas teaches a variety of peptide substitutions that increase stability, which differ from the unmodified Serp-1 (See table 3). Furthermore, regarding the in vivo stability, the claims are all drawn to products, not methods of making or using the product, so the art is not required to teach a future step of administering the peptide to a subject to observe stability.
As such, the teaching of Lucas anticipate the instant claims by teaching all of the structural limitations of the claims, and Dai provides further evidence that Serp-1 variants are stable at temperatures above 25⁰C.
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.
Claim(s) 1, 2, 8-15, 19, 21, 26, 29, 32, 33, 35, 44, 49 and 50 are rejected under 35 U.S.C. 103 as being unpatentable over Lucas et al. in view of Dai et al., as applied to claims 1, 2, 8-11, 13-15, 19, 21, 26, 29, 32, 33, 35, 44, 49 and 50 above, and in further view of Wang et al. (Process Biochemistry 63 (2017) 154–162).
The teachings of Lucas as evidenced by Dai have been described supra.
The difference between the prior art and instant claims is that Lucas does not teach wherein the PEG is branched.
Wang teaches that the in vitro and in vivo bioactivities of mono-PEG-HV2 showed that branched PEG-HV2 had higher therapeutic efficacy than linear PEG-HV2 with identical molecular weight. The in vivo bioactivity of mono-B-PEG40k-HV2 (mono-PEG-HV2 derived from 40 kDa branched mPEG2-NHS) had a markedly longer duration in vivo than did unmodified HV2 (abstract). Wang further teaches that branched PEG displays higher steric hindrance, which can prevent the PEG from coupling to the protein at the bioactive and buried sites, which improves the retained bioactivity of mono-PEG-protein conjugates and the selectivity of PEGylation by reducing the formation of multi-PEG-protein conjugates (p. 154, Col. 2). This reference also teaches that branched PEG has a greater shielding effect on a protein surface, resulting in higher proteolytic resistance and lower immunogenicity of mono-PEG-protein conjugates (p. 154, Col. 2).
As such, it would have been obvious to one of ordinary skill in the art at the filing date of the invention to modify the disclosure of Lucas and used a branched PEG instead of a linear PEG, in order to provide the advantage of retaining bioactivity by preventing multi-PEG protein conjugates and shielding protein surface to impart proteolytic resistance. One would be motivated to do so with the peptides of Lucas because Wang teaches that the in vitro and in vivo bioactivities of mono-PEG proteins showed that branched PEG-proteins had higher therapeutic efficacy than linear PEG proteins with identical molecular weight. There is a reasonable expectation of success that the bioactivity of a branched PEG conjugated to Serp-1 of Lucas will have a higher therapeutic efficacy and duration than the linear PEG.
Non-Statutory 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.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 2, 8-11, 13, 15, 19, 21, 26, 29, 32, 33, 35, 44, 49 and 50 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/845,915 (reference application) as evidenced by Dai. Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of ‘915 teaches treating a subject with an acute respiratory syndrome, comprising: administering to the subject a modified Serp-1 protein comprising at least one therapeutic enhancing moiety, wherein the modified Serp-1 protein is biologically active. As to the stability of the Serp-1 protein, as discussed above, it is an inherent property of the composition itself, and Dai provides supporting evidence to show that Serp-1 is stable at temperatures above 25⁰C.
Instant claim 2 is met because claim 2 of ‘915 teaches Serp-1 that is at least 90% identical to SEQ ID NO: 1, which is the same as instantly claimed SEQ ID NO: 1. Instant claims 8-11 and 13 are met because claim 4 teaches a water soluble polymer and claim 6 teaches that it is PEG. Instant claim 15 is met because claim 6 teaches that the PEG is 50-100,000 Da. Instant claim 19 is met by claim 7, which teaches that the therapeutic enhancing moiety is linked to lysine or cysteine and instant claim 21 is met because claim 8 of ‘915 teaches that the therapeutic enhancing moiety is attached near the N or C terminus. Instant claim 26 is met because the term “linker” is broadly defined in the specification [00124-00125] as a group or a bond caused by a chemical reaction, as discussed above. Instant claim 29 is met because the PEG is covalently connected to the peptide, as it may be attached to lysine, cysteine and either terminus. Claims 32, 33, and 35 are met because the Serp-1 of these claims is a product by process, and the method by which the Serp-1 is produced does not patentably distinguish the product itself from the prior art. The MPEP states: "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted) (Claim was directed to a novolac color developer. The process of making the developer was allowed. The difference between the inventive process and the prior art was the addition of metal oxide and carboxylic acid as separate ingredients instead of adding the more expensive pre-reacted metal carboxylate. The product-by-process claim was rejected because the end product, in both the prior art and the allowed process, ends up containing metal carboxylate. The fact that the metal carboxylate is not directly added, but is instead produced in-situ does not change the end product.). Furthermore, "[b]ecause validity is determined based on the requirements of patentability, a patent is invalid if a product made by the process recited in a product-by-process claim is anticipated by or obvious from prior art products, even if those prior art products are made by different processes." Amgen Inc. v. F. Hoffmann-La Roche Ltd., 580 F.3d 1340, 1370 n. 14, 92 USPQ2d 1289, 1312, n. 14 (Fed. Cir. 2009). See also Biogen MA Inc. v. EMD Serono, Inc., 976 F.3d 1326, 1334, 2020 USPQ2d 11129 (Fed. Cir. 2020) ("Biogen is certainly correct that the scope of composition and method of treatment claims is generally subject to distinctly different analyses. But where, as here, the novelty of the method of administration rests wholly on the novelty of the composition administered, which in turn rests on the novelty of the source limitation, the Amgen analysis will necessarily result in the same conclusion on anticipation for both forms of claims."); United Therapeutics Corp. v Liquidia Techs., Inc., 74 F.4th 1360, 1373, 2023 USPQ2d 862 (Fed. Cir. 2023) (the court held that product-by-process claims were properly rejected as "anticipated by a disclosure of the same product irrespective of the processes by which they are made."); and Purdue Pharma v. Epic Pharma, 811 F.3d 1345, 117 USPQ2d 1733 (Fed. Cir. 2016). “ (See MPEP 2113).
As such, unless there are significant differences in the final product, the fact that the Serp-1 was produced or secreted by eukaryotic cells does not distinguish the instantly claimed product from the product of ‘915. Instant claims 44, 49 and 50 are met because, as discussed above, the half-life and stability are inherent to the product itself, and the claims of ‘915 are drawn to the exact same PEGylated Serp-1 as the instant claims (See MPEP 2112). As such, it would be expected to have the same inherent properties, absent evidence to the contrary.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 2, 8-11, 13-15, 19, 21, 26, 29, 32, 33, 35, 44, 49 and 50 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-20 of copending Application No. 18/845,915 in view of Lucas as evidence by Dai.
The difference between the prior art and instant claim 14 is that ‘915 does not teach adding acyl and alkyl groups to the Serp-1 protein.
The teachings of Lucas as evidenced by Dai have been described supra.
Specifically, Lucas teaches that a substituent (moiety) can be an acyl group or a substituted or unsubstituted amine group (e.g., the substituent at the N-terminus can be an acyl group and the C-terminus can be amidated a substituted amine group having a lower alkyl moiety (p. 9, lines 19-25).
As such, it would have been obvious to one of ordinary skill in the art at the time of the invention to have taken the Serp-1 of claim 1 of ‘915 and used and acyl or alkyl group as the therapeutic enhancing moiety because Lucas teaches that such groups are effective for the same peptides and the same purpose of improving therapeutic properties. One would be motivated to do so because Lucas teach that these modifications adding acyl or alkyl will retain bioactivity and enhance therapeutic properties when conjugated to the Serp-1 peptide. As such, there is a reasonable expectation of success that the Serpin-1 of ‘915 will be active and stable when conjugated to an alkyl or acyl.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 2, 8-13, 15, 19, 21, 26, 29, 32, 33, 35, 44, 49 and 50 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-20 of copending Application No. 18/845,915 as evidenced by Dai and in view of Wang.
The difference between the instant claims and those of ‘915 is that the claims of ‘915 do not teach a branched PEG.
The teachings of ‘915, Dai and Wang have been described supra.
Based on Wang’s teachings regarding branched PEG advantages, it would have been obvious to one of ordinary skill in the art at the time of the invention to modify the disclosure of ‘915 and used a branched PEG instead of a linear PEG, to provide the advantage of retaining bioactivity by preventing multi-PEG protein conjugates and shielding protein surface to impart proteolytic resistance. One would be motivated to use branched PEG with the peptides of ‘915 because Wang teaches that the in vitro and in vivo bioactivities of mono-PEG proteins showed that branched PEG proteins had higher therapeutic efficacy than linear PEG proteins with identical molecular weights. As such, there is a reasonable expectation of success that the in vivo bioactivity of a branched PEG conjugated to the Serp-1 of ‘915 will have a higher therapeutic efficacy and duration.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANETTE M LIEB whose telephone number is (571)270-3490. The examiner can normally be reached M-F 10-7.
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/JEANETTE M LIEB/Primary Examiner, Art Unit 1654