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 .
Election/Restrictions
Claims 1-2, 5, 8-9, 13, 18, 23-25, 27-30, 33, and 35-39 are currently pending. Claims 18, 23-25, 27-30, 33, and 35-39 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-2, 5, 8-9, and 13 are directed to the elected invention and have been examined per the species election requirement.
Amendments
Claim 1 now requires that at least one amino acid residue of the peptide is modified to comprise an acetyl group, a fluorenylmethoxy carbonyl group, a formyl group, a palmitoyl group, a myristyl group, a stearyl group, or polyethylene glycol.
Claim 9 has been amended to recite the generic term levetiracetam.
Specification
Previous objection to the specification
The specification was previously objected to for containing hyperlinks and for containing trademarks without accompanied generic terminology. Applicant has made the appropriate correction to the impermissible hyperlink but has not made the appropriate correction to the use of trade names. Therefore, the objection to the specification is maintained.
Maintained objection to the specification
The specification is objected to because of the use of the term “Keppra®”, which is a trade name or a mark used in commerce. Although the appropriate correction has been made to distinguish this word as a trademark, the term should be accompanied by the generic terminology (i.e., should define the composition of Keppra® (levetiracetam). Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
For the purposes of amendment, the Examiner notes that any such amendment to include the generic terminology for Keppra® would not introduce new matter in the specification because Keppra®, at the time of filing, was widely known to be a brand name for levetiracetam.
Appropriate correction is required.
Claim Objections
Previous objection to the claims
Claim 9 was objected to for a minor informality and applicant has made the appropriate correct. Therefore, the objection to claim 9 is withdrawn.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Previous rejection under 35 U.S.C. § 112(b)
RE: Rejection of claim 9 under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint, regards as the invention.
Claim 9 was rejected for reciting a trademark/trade name (Keppra®) to describe a particular material or product. Applicant has retained the trademark language and has argued that “the meaning of Keppra® is well-established in the literature and has a definite meaning to a person of ordinary skill in the art at the time of invention” (Remarks, p. 10, par. 4). Specifically, applicant asserts that Keppra® is the brand name for levetiracetam for use in treating seizures and levetiracetam is commonly known by the brand name Keppra®. As such, applicant requests that the rejection be withdrawn.
Applicant’s arguments have been fully considered but a rejection under 35 U.S.C. § 112(b) is still applicable to the amended claims. Specifically, although applicant has appropriately amended the claim such that the structure is defined by the generic terminology for Keppra®’s active ingredient (levetiracetam) rather than by the trade name, the use of the parenthetical with the trade name after “levetiracetam” renders it unclear if applicant’s claim implies that only the Keppra® formulation of levetiracetam is encompassed by the claim. In other words, does the scope of the claim encompass levetiracetam, Keppra®, or does it also include the generic formulation of the drug?
In the interest of preserving trademark rights, it is not permissible to use the trade name as an interchangeable term with the generic name. In other words, the trade name should not be used to identify the levetiracetam molecule. Moreover, it is noted that Keppra® may be commonly understood to refer to levetiracetam but Keppra® is a formulation including other components such as colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, polyethylene glycol 3350, polyethylene glycol 6000, polyvinyl alcohol, talc, titanium dioxide, and artificial dyes (KEPPRA® (levetiracetam), www.accessdata.fda.gov/drugsatfda_docs/label/2009/021035s078s080%2C021505s021s024lbl.pdf (accessed September 2025), FDA Label Search).
Because the scope of the claim is not clearly defined, the claim is indefinite and a new ground of rejection is set forth below.
New ground of rejection under 35 U.S.C. § 112(b)
Claim 9 is rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint, regards as the invention.
Claim 9 contains the trademark/trade name Keppra® in parenthesis following the generic term “levetiracetam”. This parenthetical language of this claim renders the claim indefinite. Specifically, it is not clear if the claim requires the Keppra® formulation of levetiracetam or is merely limiting to levetiracetam and providing Keppra® as an exemplary source of the levetiracetam. In other words, must the composition contain Keppra® in order to read on the claimed invention or is levetiracetam from any other source (such as a generic manufacturer) considered to be encompassed by the claim?
In the interest of compact prosecution, this claim is interpreted to merely require levetiracetam. As discussed in MPEP § 2173.05(u), if a trademark or trade name appears in a claim and is not intended as a limitation in the claim, the question of why it is in the claim should be addressed. It is recommended that applicant simply remove the trade name from the claim. This line of amendment would be consistent with Eli Lilly & Co. v. Apotex, Inc., 837 Fed. Appx. 780, 784-85, 2020 USPQ2d 11531 (Fed. Cir. 2020), wherein Eli Lilly removed the tradename and simply replaced it with the generic terminology in order to overcome a rejection under pre-AIA 35 U.S.C. § 112, second paragraph.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Previous rejections under 35 U.S.C. § 101
RE: Rejection of claims 1-2, 5, 8-9, and 13 under 35 U.S.C. 101 because the claimed invention is directed to a law of nature and natural phenomenon without significantly more.
Claims 1-2, 5, 8-9, and 13 were rejected for reciting natural products without significantly more. Applicant traverses this rejection by arguing that the amended claims are subject matter eligible because each of the claims require a peptide wherein at least one amino acid residue of the peptide is modified to comprise an acetyl group, a fluorenylmethoxy carbonyl group, a formyl group, a palmitoyl group, a myristyl group, a stearyl group, or polyethylene glycol which allegedly does not occur in nature as a single molecule. Additionally, applicant asserts that these modifications improve stability and stability of a non-naturally occurring composition is a marked difference.
Applicant’s arguments have been fully considered but are not sufficient to render the claimed compositions subject matter eligible for the following reasons.
The post-translational modifications required by the amended claims encompass post-translational modifications which occur in nature. For example, Kitamura et al. (Biochemical Journal, 2023, Vol. 480, pages 1241-1265; hereinafter Kitamura) reviews in vivo post-translational modifications and teaches acetylation, formylation, and palmitoylation as post-translational modifications found in the human proteome (p. 1243-1246). Kitamura teaches that “the vast majority of PTMs are derived from non-enzymatic reactions and driven through site availability, local electrostatics and mass action” (p. 1253, par. 4). Moreover, “many PTMs may simply be along for the ride, having no measurable impact of protein function” (p. 1255, par. 3). Lys acetylation is a “widely ubiquitous PTM” and many of these modifications do not impact protein function nor physiological outcome (Id.). Current estimates indicate that 20-50% of all proteins are acetylated (Id.).
Therefore, because modifications such as the widely ubiquitous acetylation occur in nature due to site availability, local electrostatics, and mass action, it is reasonable to conclude that the naturally-occurring peptide comprising the sequence of SEQ ID NO: 1 is acetylated in nature on at least one of its amino acids. The peptide is clearly not markedly different from its natural counterpart because the natural counterpart is similarly acetylated on at least one amino acid residue. And even if the peptide is one of the peptides which are not acetylated in nature, Kitamura demonstrates that merely adding post-translational modification such as an acetyl group does not necessarily improve the characteristics of the peptide such that they are markedly different from the natural counterpart. This is evidenced by Kitamura’s teachings that many PTMs are along for the ride and have no measurable impact on protein function or physiological outcome. In order to support a conclusion of markedly different characteristics, applicant must demonstrate that each of the proposed modifications would impart the alleged markedly different characteristic on every amino acid covered by the scope of “at least one amino acid”.
Accordingly, the claims still encompass products of nature and require rejection under 35 U.S.C. § 101. In the interest of addressing applicant’s amendments to the claims, the rejection of record is withdrawn and a new ground of rejection is made below.
Claims 1-2, 5, 8-9, and 13 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature and natural phenomenon without significantly more.
The instant claims recite laws of nature and natural phenomena. These judicial exceptions (JEs) are not integrated into a practical application and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception as explained below:
Subject Matter Eligibility Guidance
A three-step inquiry has been established to determine subject matter eligibility under 35 U.S.C. 101, in accordance with MPEP § 2106:
Step (1): Is the claim directed to a process, machine, manufacture, or composition of matter?
Step (2A): Is the claim directed to a law of nature, natural phenomenon (product of nature), or an abstract idea?
Prong 1 – Does the claim recite a law of nature, natural phenomenon, or an abstract idea?
Product of Nature Definition
When a law of nature or natural phenomenon is claimed as a physical product, the courts have often referred to the exception as a "product of nature". See Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 580, 106 USPQ2d 1972, 1975 (2013); University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 758-59, 113 USPQ2d 1241, 1243 (Fed. Cir. 2014). As explained in those decisions, products of nature are considered to be an exception because they tie up the use of naturally occurring things, but they have been labeled as both laws of nature and natural phenomena. See Myriad Genetics, Inc., 569 U.S. at 590-91, 106 USPQ2d at 1979.
The Markedly Different Characteristics Analysis
The first step in the analysis is to select the appropriate counterpart to the nature-based product. When the nature-based product is derived from a naturally occurring thing, then the naturally occurring thing is the counterpart. See MPEP § 2106.04(c)(II)(A).
The second step in the analysis is to identify appropriate characteristics to compare. Appropriate characteristics must be possessed by the claimed product, because it is the claim that must define the invention to be patented. Cf. Roslin, 750 F.3d at 1338, 110 USPQ2d at 1673. See MPEP § 2106.04(c)(II)(B).
The final step in the markedly different characteristics analysis is to compare the characteristics of the claimed nature-based product to its naturally occurring counterpart in its natural state, in order to determine whether the characteristics of the claimed product are markedly different. See MPEP § 2106.04(c)(II)(C).
Prong 2 – If the claim recites a judicial exception, does it recite additional elements that integrate the judicial exception into a practical application?
Limitations that are indicative of integration into a practical application include:
Improvements to the functioning of a computer, or to any other technology or technical field. See MPEP § 2106.05(a);
Applying the judicial exception with, or by use of, a particular machine. See MPEP § 2106.05(b);
Effecting a transformation or reduction of a particular article to a different state or thing. See MPEP § 2106.05(c);
Applying or using a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition. See MPEP § 2106.05(d);
Applying or using the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception. See MPEP § 2106.05(e).
Step (2B). If the recited judicial exception is not integrated into a practical application, does the claim recite additional elements that amount to significantly different than the judicial exception such that they provide an inventive concept? This step includes evaluation of the same considerations under Step (2A), Prong 2, as well as two additional considerations:
Adding a specific limitation or combination of limitations that are not well-understood, routine, conventional activity in the field, which is indicative that an inventive concept may be present; and
Simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, which is indicative that an inventive concept may not be present.
Analysis
Step (1)(direction to a process, machine, manufacture, or composition of matter):
Claims 1-2, 5, 8-9, and 13 are directed to compositions of matter, which is a statutory category.
Therefore, the answer to this step for claims 1-2, 5, 8-9, and 13 is yes.
Step (2A) Prong 1 (recitation of a law of nature, natural phenomenon, or an abstract idea):
Claims 1-2, 5, 8-9, and 13 are directed to compositions comprising a peptide comprising the sequence of SEQ ID NO: 1. SEQ ID NO: 1 is representative ATAD1 (human ATPase family AAA domain-containing protein)(Specification, p. 20, lines 9-19). Because the recited sequence is the human protein sequence, the peptide is a product of nature (a law of nature and natural phenomenon).
Claims 1-2, 5, 8, and 13 only comprise the natural product per se and therefore are not markedly different from the naturally occurring ATAD1 protein.
Claim 1 further requires that at least one amino acid residue of the peptide is modified to comprise an acetyl group, a fluoroenylmethoxy carbonyl group, a formyl group, a palmitoyl group, a myristyl group, a stearyl group, or polyethylene glycol.
Kitamura et al. (Biochemical Journal, 2023, Vol. 480, pages 1241-1265) teaches that “the vast majority of PTMs are derived from non-enzymatic reactions and driven through site availability, local electrostatics and mass action” (p. 1253, par. 4). Moreover, “many PTMs may simply be along for the ride, having no measurable impact of protein function” (p. 1255, par. 3). Lys acetylation is a “widely ubiquitous PTM” and many of these modifications do not impact protein function nor physiological outcome (Id.). Current estimates indicate that 20-50% of all proteins are acetylated (Id.).
Therefore, because modifications such as the widely ubiquitous acetylation occur in nature due to site availability, local electrostatics, and mass action, it is reasonable to conclude that the naturally-occurring peptide comprising the sequence of SEQ ID NO: 1 is acetylated in nature. The peptide is clearly not markedly different from its natural counterpart because the natural counterpart is similarly acetylated on at least one amino acid residue. And even if the claimed peptide is one of the peptides which is not acetylated in nature, Kitamura demonstrates that merely adding post-translational modification such as an acetyl group does not necessarily improve the characteristics of the peptide such that they are markedly different from the natural counterpart. This is evidenced by Kitamura’s teachings that “many PTMs” are along for the ride and have no measurable impact on protein function or physiological outcome.
Claim 9 further includes baclofen or levetiracetam. Although baclofen and levetiracetam are not naturally occurring, that does not necessarily mean that the claim is subject matter eligible. Where the claim is to a nature-based product in combination with non-nature-based elements (e.g., a claim to "a yogurt starter kit comprising Lactobacillus in a container with instructions for culturing Lactobacillus with milk to produce yogurt"), the markedly different characteristics analysis should be applied only to the nature-based product limitation (MPEP § 2106.04(c)(I)(A)). In this case, there is no evidence that the recited protein is markedly different in structure, property, and/or function as a result of being combined with baclofen or levetiracetam.
Therefore, the answer to this prong for claims 1-2, 5, 8-9, and 13 is yes.
Step (2A) Prong 2 (recitation of additional elements that integrate the JE into a practical application):
As discussed above, claims 1-2, 5, 8, and 13 are directed to the natural product per se, accordingly, they cannot integrate the JE into a practical application as discussed below.
Claims 1-2 are directed to the sequence of the peptide and the modification to at least one amino acid residue of the peptide does not necessarily integrate the judicial exception. There is no evidence that every modification to every “at least one” amino acid would integrate the judicial exception such as by transforming or reducing the JE to a different state or thing.
Claims 5 and 8 are directed to properties of the peptide.
The sequence and properties of a peptide do not integrate the JE into a practical application.
Claim 9 further requires the composition to comprise baclofen or levetiracetam. Including an additional agent such as baclofen or levetiracetam does not integrate the JE into a practical application such as by effecting a transformation or reduction of a particular article to a different state or thing.
Claim 13 requires that the composition is a “pharmaceutical composition”. Merely calling a composition a “pharmaceutical composition” does not integrate the JE such as by applying or using a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition.
Therefore, the answer to this prong for claims 1-2, 5, 8-9, and 13 is no.
Step (2B)(recitation of additional elements that amount to significantly different than the JE such that they provide an inventive concept):
Claims 1-2 are directed to the sequence of the peptide. And although the claims require at least one amino acid residue to comprise one of the recited modifications, this does not necessarily provide an inventive concept. For example, as discussed above, Kitamura demonstrates that at least some of these modifications occur in nature. Moreover, Roberts et al. (Advanced Drug Delivery Reviews, 2002, Vol. 54, pages 459-476) teaches that those in biomedical, biotechnical and pharmaceutical communities have become quite familiar with the improved pharmacological and biological properties that are associated with the covalent attachment of polyethylene glycol (PEG) to therapeutically useful polypeptides (p. 460, left col., par. 3). PEG conjugation can shield antigenic epitopes of the polypeptide, thus reducing reticuloendothelial clearance and recognition by the immune system (Id.). Additionally, PEG reduces degradation by proteolytic enzymes and increases the apparent size of the polypeptide, thus reducing renal filtration and altering biodistribution (Id.). Thus, the modifications on at least one amino acid do not provide an inventive concept because the record is clear that modifications encompassed by these claims were either known to be naturally occurring or were “quite familiar” to people having ordinary skill in the art.
Claims 5 and 8 are directed to properties of the peptide.
Merely describing the sequence and properties of a peptide do not provide an inventive concept.
Claim 9 further requires the composition to comprise baclofen or levetiracetam. Including an additional agent such as baclofen or levetiracetam does not amount to significantly different from the JE. For example, Chun et al. (US 2006/0014244 A1; cited in the four-page IDS filed on 12/12/2022) teaches pharmaceutical compositions comprising ATPase-like proteins ([0199]). Chun’s proteins include the protein encoded by SEQ ID NO: 2 ([0068]). Chun’s SEQ ID NO: 2 is 100% identical to the peptide comprising the sequence of SEQ ID NO: 1, as claimed by applicant (see below).
Chun further teaches that the composition can comprise “supplementary active compounds” ([0199]). Accordingly, it was previously known that the JE could be combined with other active compounds and this additional element therefore does not provide an inventive concept because it is well-understood and routine activity.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Previous rejection under 35 U.S.C. § 102
RE: Rejection of claims 1-2, 5, 8, and 13 under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Chun et al. (US 2006/0014244 A1; cited in four-page IDS filed on 12/12/2022).
Applicant traverses the rejection of record by arguing that the claims, as amended, overcome the teachings of Chun because Chun allegedly does not teach the peptide wherein at least one amino acid residue of the peptide is modified to comprise an acetyl group, a fluorenylmethoxy carbonyl group, a formyl group, a palmitoyl group, a myristyl group, a stearyl group, or polyethylene glycol.
Applicant’s argument has been fully considered and is sufficient, at least, to overcome the anticipation rejection. Specifically, Chun does not explicitly teach such a modification to the peptide and therefore the claims are not anticipated by Chun. Accordingly, the rejection under 35 U.S.C. § 102 is withdrawn.
Nonetheless, for the reasons discussed in the rejection under 35 U.S.C. § 103 below, it would have been obvious to have modified the teachings of Chun in order to arrive at the claimed peptide. As such, new grounds of rejection are made below.
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.
Previous rejection under 35 U.S.C. § 103
RE: Rejection of claims 1-2, 5, 8, and 13 under 35 U.S.C. 103 as being unpatentable over Chun et al. (US 2006/0014244 A1; cited in four-page IDS filed on 12/12/2022) in view of Braverman et al. (Molecular Genetics and Metabolism, 2016, Vol. 117(3), pages 313-321).
As discussed above, Chun does not teach the peptide wherein at least one amino acid residue of the peptide is modified to comprise an acetyl group, a fluorenylmethoxy carbonyl group, a formyl group, a palmitoyl group, a myristyl group, a stearyl group, or polyethylene glycol. Braverman does not remedy this deficiency. As such, the rejection under 35 U.S.C. § 103 is withdrawn.
An updated prior art search was performed and Roberts is considered to remedy this deficiency and render obvious the recited modification to the peptide of claim 1. As such, new grounds of rejection are made below.
New ground of rejection under 35 U.S.C. § 103
Claims 1-2, 5, 8, and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Chun et al. (US 2006/0014244 A1; cited in four-page IDS filed on 12/12/2022) in view of Roberts et al. (Advanced Drug Delivery Reviews, 2002, Vol. 54, pages 459-476).
Chun et al. (hereinafter Chun) teaches novel ATPase-like molecules (abstract; [0058]). Specifically, Chun teaches that enzymes that bind to and hydrolyze ATP play a pivotal role in translating chemically stored energy into biological activity ([0058]). In particular, Chun provides isolated nucleic acid molecules comprising nucleic acid sequences encoding the amino acid sequences shown in SEQ ID NO: 2 and ATPase-like polypeptides having an amino acid sequence encoded by a nucleic acid molecule described therein ([0068]). Chun’s ATPases are useful for modulating agents in a variety of cellular processes including organelle biogenesis, cell-cycle regulation, vesicle-mediated transport, assembly of proteins through membranes, peroxisome biogenesis, protein sorting, gene expression, and 26S proteasome function ([0070]).
Regarding claim 1, Chun teaches pharmaceutical compositions comprising ATPase-like proteins ([0199]). Chun’s proteins include the protein encoded by SEQ ID NO: 2 ([0068]). Chun’s SEQ ID NO: 2 is 100% identical to the peptide comprising the sequence of SEQ ID NO: 1, as claimed by applicant (see below).
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Chun differs from claim 1 because it does not teach the peptide wherein at least one amino acid residue of the peptide is modified to comprise an acetyl group, a fluorenylmethoxy carbonyl group, a formyl group, a palmitoyl group, a myristyl group, a stearyl group, or polyethylene glycol.
Nonetheless, Roberts et al. (hereinafter Roberts) reviews the use of polyethylene glycol (PEG) in peptide pharmaceutical development (abstract). Roberts teaches that the use of proteins and peptides as human therapeutics has expanded in recent years and although more biopharmaceuticals are in development than ever before, many of these have problems that are typical of polypeptide therapeutics including short circulating half-life, immunogenicity, proteolytic degradation, and low solubility (p. 460, left col., par. 1-2). Several strategies have emerged as ways to improve the pharmacokinetic and pharmacodynamic properties of biopharmaceuticals (p. 460, left col., par. 2). Roberts teaches that those in biomedical, biotechnical and pharmaceutical communities have become quite familiar with the improved pharmacological and biological properties that are associated with the covalent attachment of polyethylene glycol (PEG) to therapeutically useful polypeptides (p. 460, left col., par. 3). PEG conjugation can shield antigenic epitopes of the polypeptide, thus reducing reticuloendothelial clearance and recognition by the immune system (Id.). Additionally, PEG reduces degradation by proteolytic enzymes and increases the apparent size of the polypeptide, thus reducing renal filtration and altering biodistribution (Id.).
Since Chun teaches a pharmaceutical composition comprising ATPase-like proteins including proteins having 100% identity to SEQ ID NO: 1 and because Roberts teaches that persons of ordinary skill in the art are “quite familiar” with the improved properties associated with PEGylation of therapeutic peptides including the ability of PEG to shield antigenic epitopes, reduce degradation, and decrease renal filtration, it would have been obvious to have improved Chun’s peptide by modifying at least one amino acid residue of the peptide to comprise a polyethylene glycol. The modification would have predictably resulted in a peptide with improved pharmacological properties, thus improving its suitability as a therapeutic peptide. This obviousness is based upon the “Some Teaching, Suggestion, or Motivation in the Prior Art That Would Have Led One of Ordinary Skill To Modify the Prior Art Reference or To Combine Prior Art Reference Teachings To Arrive at the Claimed Invention” rationale set forth in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007). See MPEP 2143(I)(G).
Thus, claim 1 is obvious over Chun in view of Roberts.
Regarding claim 2, as discussed in the Election/Restriction section of this action, the claims stand examined under the species election (“SEQ ID NO: 1”). For the reasons discussed above, Chun teaches compositions comprising the elected species.
Regarding claims 5 and 8, the recited limitations are inherent properties to the polypeptide previously described by Chun. Because Chun describes the same composition, it must have the same properties (MPEP § 2112.01(I)). In other words, Chun’s polypeptide must inherently be capable of recognizing, binding and removing one or more peroxins embedded in an outer mitochondrial membrane of a cell (claim 5) wherein the one or more peroxins is PEX13, PEX11, PEX2, PEX17, PEX3, PEX22, PEX25, PEX14, PEX4 (claim 8). And although Chun may not have taught the capability to recognize, bind, and remove the recited peroxins, "the 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" (MPEP § 2112(I)). There is no requirement that Chun (or any other person) would have recognized this property, and the previously known polypeptide does not become patentably new simply by recognizing this property.
Regarding claim 13, as discussed above, Chun’s composition is a pharmaceutical composition ([0199]).
Claims 1-2, 5, 8-9, and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Chun et al. (US 2006/0014244 A1; cited in four-page IDS filed on 12/12/2022) in view of Roberts et al. (Advanced Drug Delivery Reviews, 2002, Vol. 54, pages 459-476) and Braverman et al. (Molecular Genetics and Metabolism, 2016, Vol. 117(3), pages 313-321).
The teachings of Chun and Roberts are set forth above and applied herein. Chun in view of Roberts is found to render obvious claims 1-2, 5, 8, and 13.
Regarding claim 9, as discussed above, Chun in view of Roberts renders obvious the composition comprising the peptide of SEQ ID NO: 1 and further comprising modification of at least one amino acid residue to comprise polyethylene glycol. Chun also teaches that the ATPases of its disclosure are known to be involved in peroxisome biogenesis ([0060]) and can be used as modulating agents for peroxisome biogenesis ([0070]). Chun further teaches that the composition can comprise “supplementary active compounds” ([0199]).
Chun, however, does not teach that the composition further comprises a therapeutic agent, wherein the therapeutic agent is baclofen or levetiracetam.
Braverman et al. (hereinafter Braverman) reviews the state of peroxisome biogenesis disorders and teaches that peroxisome biogenesis disorders in the Zellweger spectrum (PBD-ZSD) are genetic disorders caused by mutations in PEX genes (abstract). Braverman teaches that neonatal seizures are seen in “nearly all severely affected PBD-ZSD patients” and have been reported in 23% of less severe patients (p. 8, par. 2). Mild and intermediate seizures are also seen later in life (p. 18, Table 1). For seizure control, standard antiepileptic drugs (AEDs) may be used with no types of AEDs being contraindicated for PBD-ZSD seizure control (p. 5, par. 4 through p. 6, par. 1). Common medications used to control seizures in children affected by PBD-ZSD are levetiracetam, phenobarbital, clonazepam, topiramate, and lamotrigine (p. 8, par. 2).
Accordingly, because Chun in view of Roberts renders obvious the composition comprising the peptide defined in claim 1 which can be used for modulating peroxisome biogenesis and which can further comprise “supplementary active compounds”, and because Braverman teaches that AEDs such as levetiracetam are commonly used to treat peroxisome biogenesis-related disorder-associated seizures, it would have been obvious to have combined the two previously known compositions to arrive at the composition of claim 9. Each of the components of the combined composition merely perform the same function as they do separately (i.e., the peptide performs its ATPase function and the levetiracetam performs its anti-epileptic function). Additionally, the modification would have been expected to result in an improved therapeutic composition for biogenesis disorders such as by treating the underlying peroxisome biogenesis dysfunction and treating the common seizure symptom. There would have been a reasonable expectation of success because Chun contemplates the combination of its peptides with additional active compounds and because, as discussed above, the compositions are merely performing the same function as they do independently. This obviousness is based upon the “Combining Prior Art Elements According to Known Methods to Yield Predictable Results” rationale set forth in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007). See MPEP 2143(I)(A).
Thus, claim 9 is obvious over Chun in view of Roberts and Braverman.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/GRANT C CURRENS/Examiner, Art Unit 1651
/MICHELLE F. PAGUIO FRISING/Primary Examiner, Art Unit 1651