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 .
Response to Election/Restriction filed on April 9, 2026 is acknowledged.
Claims 1-2, 6-8, 12, 15, 17-18, 20, 22, 26-27, 29-32, 34, 37 and 42 are pending in this application.
Restriction
Applicant’s election without traverse of Group 1 (claims 1-2, 6-8, 12, 15, 17-18, 20, 22, 26 and 31) and the election without traverse of SEQ ID NO: 1 as the fully defined API5 protein and a His tag as a species of moiety in the reply filed on April 9, 2026 is acknowledged. Restriction is deemed to be proper and is made FINAL in this office action. Claims 27, 29-30, 32, 34, 37 and 42 are withdrawn from consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions, there being no allowable generic or linking claim. Applicant indicates claims 1-2, 6-8, 12 and 31 read on the elected species. Claim 12 recites SEQ ID NOs: 3 and 6, which do not read on SEQ ID NO: 1, therefore, claim 12 is withdrawn from further consideration. Claims 12, 15, 17-18, 20, 22 and 26 are withdrawn from further consideration as being drawn to nonelected species. Claims 1-2, 6-8 and 31 are examined on the merits in this office action.
Objections
5. The abstract is objected to for the following minor informality:
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words. It is important that the abstract not exceed 150 words in length since the space provided for the abstract on the computer tape used by the printer is limited. The form and legal phraseology often used in patent claims, such as "means" and "said," should be avoided. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, "The disclosure concerns," "The disclosure defined by this invention," "The disclosure describes," etc.
In the instant case, the abstract recites, “The disclosure provides, among other things...” at line 1 of the abstract. Applicant should correct these informalities. See MPEP 608.01(b). For example, the abstract may be amended to recite, “Recombinant API5 proteins…are described.”
Please note, the specification has not been checked to the extent necessary to determine the presence of all possible error. Applicant's cooperation is required in correcting any errors of which applicant may become aware in the specification. MPEP § 608.01.
Rejections
35 U.S.C. 101
6. 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.
7. Claims 1-2 and 31 are rejected under 35 U.S.C. 101 because the claimed invention is directed to natural phenomenon without significantly more. Claim(s) 1-2 recite(s) a naturally occurring peptide/protein fragment, which is not markedly different from its naturally occurring counterpart because it conveys the same amino acid sequences at the residues 1-524 for instant SEQ ID NO: 1 of the naturally occurring protein, as evidenced by UniProt A02K5JEB2 is a naturally occurring protein isolated from Colobus angolensis palliates (Peter’s Angolan colobus). Claim 31 is directed to a pharmaceutical composition comprising the recombinant protein comprising SEQ ID NO: 1 and a pharmaceutically acceptable carrier or excipient. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the following reasons. This judicial exception is not integrated into a practical application because the peptide being claimed is naturally occurring. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because for the following reasons.
The rationale for this determination is explained below and is based on the analysis presented in the USPTO’s “2014 Interim Eligibility Guidance” as set forth on December 16, 2014, Revised Guidance set forth on May 2016, and 2019 Revised patent Subject Matter Eligibility Guidance set forth on January 7, 2019. See MPEP 2106.04(c).
Step 1: Is the claim to a process, machine, manufacture or composition of matter? The instant claims are directed to a statutory patent-eligible subject matter category, a composition of matter.
Step 2a Prong 1: Is the claim directed to a law of nature, a natural phenomenon (Product of nature), or an abstract idea? The claims are directed to a natural phenomenon, specifically a natural-based product limitation.
Step 2a Prong 2: Does the claim recite additional elements that integrate the judicial exception into a practical application? This judicial exception is not integrated into a practical application because the peptide being claimed is naturally occurring.
As evidenced by UniProt A02K5JEB2 (see amino acids 1-524, enclosed), instant SEQ ID NO: 1 is a naturally occurring protein isolated from Colobus angolensis palliates (Peter’s Angolan colobus). Additionally, as evidenced by Poyet et al (US 2017/0058010 or issued as US Patent No. 10358469), instant SEQ ID NO: 1 is a naturally occurring protein isolated from Homo sapiens (see SEQ ID NO: 1).
The term “pharmaceutical composition” is not specifically defined in the specification. Although one of ordinary skill in the art would construe the limitations “pharmaceutical composition” to mean isolated or purified or having additional components, this does not render the claim markedly different from what exists in nature, because the other components may also be naturally occurring, such as water. Myriad clarified that not every change to a product will result in a marked difference, and that the mere recitation of particular words (e.g., “isolated”) in the claims does not automatically confer eligibility. Id. at 2119. See also Mayo, 132 S. Ct. at 1294 (eligibility does not “depend simply on the draftsman' s art”).
Step 2b: Does the claim recite additional elements that amount to significantly more than the judicial exception? The claims, as a whole, do not recite any additional elements that amount to significantly more than the judicial exception. Specifically, the claims do not include any elements in addition to the natural product.
In sum, when the relevant steps are analyzed, they weigh against a significant difference. Accordingly, claims 1-2 and 31 do not qualify as eligible subject matter.
Please see Example 7 (claim 1 analysis) of “Guidance” and Example 28 (claim 3 analysis) and Example 30 (claims 1-2 analyses) of “Revised Guidance”. MPEP 2106.
U.S.C. 112
8. 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.
9. Claims 1-2, 6-8 and 31 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The courts have stated:
“To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient.” MPEP 2163.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co., the court stated:
“A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials. Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284-85 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus. . . ."). Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP 2163. The MPEP does state that for generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP 2163. Although the MPEP does not define what constitute a sufficient number of representative, the Courts have indicated what do not constitute a representative number species to adequately describe a broad generic. In Gostelli, the Court determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872 F.2d at 1012, 10 USPQ2d at 1618.
In the instant case, the claims are drawn to a recombinant protein comprising an apoptosis inhibitor 5 (API5) protein, or a fragment or a variant thereof (claim 1); wherein the API5 protein comprises the amino acid sequence of SEQ ID NO: 1 or 2, or a sequence having at least 90% identity thereto (claim 2a)). The generic statements a fragment or a variant thereof of an apoptosis inhibitor 5 (API5) protein and at least 90% identity to SEQ ID NO: 1 or 2 do not provide ample written description for the compounds since the claims do not describe a single structural feature. The specification does not clearly define or provide examples of what qualify as compounds of the claimed invention.
As stated earlier, the MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic. It is unquestionable claims 1 and 2 are broad generics with respect all possible compounds encompassed by the claims. The possible structural variations are limitless to any class of peptide or a peptide-like molecule that can form amide bonds. It must not be forgotten that the MPEP states that if a peptide is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP 2163. Here, though the claims may recite some functional characteristics, the claims lack written description because there is no disclosure of a correlation between function and structure of the compounds beyond compounds disclosed in the examples in the specification. Moreover, the specification lack sufficient variety of species to reflect this variance in the genus since the specification does not provide any examples of derivatives/variants. The specification is void of organic molecules that functions as a peptide-like molecule that qualify for the functional characteristics claimed as a peptide or a peptide-like molecule or other peptidic molecules and other synthetic peptide or peptide-like molecule that can form amide bonds.
The specification discloses that “the fragment of API5 comprises the N-terminal HEAT repeat region of API5. In some embodiments, the fragment of API5 comprises residues 1-448 of SEQ ID NO: 1. In some embodiments, the fragment of API5 comprises residues 1-206 of SEQ ID NO: 1” (see paragraph [0006]). The specification discloses that “The term “fragment” in regard to polypeptides refers to a polypeptide that has an amino-terminal and/or carboxy-terminal deletion, but where the remaining amino acid sequence is identical to the corresponding positions in the full-length naturally-occurring sequence…Up to 10, up to 20, up to 30, up to 40 or more amino acids may be removed from the N and/or C terminal in this way…at least 14, at least 20, at least 50, or at least 70, 80, 90, 100, 150, 200 or 400 amino acids long” (see paragraph [0040]). The specification does not have a clear definition of what is encompassed within the “variant thereof”. Example 4 describes that API5 protects intestinal organoids and restores paneth cells. Example 4 describes SEQ ID NO: 3, a 481 residue protein sequence having a His-tag at positions 3-8 of the protein sequence. Example 5 describes what residues of API5 are necessary for protective effects. The working Examples describe SEQ ID NOs: 3-5 and 11, as fragments of API5. The specification does not describe any other fragments and what sequences are encompassed within “variant” of API5. Description of SEQ ID NOs: 3-5 and 11 is not sufficient to encompass numerous other proteins and proteases that belong to the same genus. For example, there are varying lengths, varying amino acid compositions, and numerous distinct qualities that make up the genus. Instant specification describes “the fragment of API5 comprises the N-terminal HEAT repeat region of API5. In some embodiments, the fragment of API5 comprises residues 1-448 of SEQ ID NO: 1. In some embodiments, the fragment of API5 comprises residues 1-206 of SEQ ID NO: 1” (see paragraph [0006]). The specification discloses that “The term “fragment” in regard to polypeptides refers to a polypeptide that has an amino-terminal and/or carboxy-terminal deletion, but where the remaining amino acid sequence is identical to the corresponding positions in the full-length naturally-occurring sequence…Up to 10, up to 20, up to 30, up to 40 or more amino acids may be removed from the N and/or C terminal in this way…at least 14, at least 20, at least 50, or at least 70, 80, 90, 100, 150, 200 or 400 amino acids long” (paragraph [0040]). Thus, according to instant definition of “fragment”, the fragment may have up to 10, 20, 30, 40 or more amino acids may be removed from the N and/or C terminal ends. Thus, a fragment may be any dipeptide (two amino acids) within SEQ ID NO: 1 up to 523 residues (instant SEQ ID NO: 1 is a 524mer protein). Additionally, a variant may have multiple different amino acid substitutions, additions, deletions and non-natural amino acids in the protein sequence. Yampolsky et al (Genetics, 2005, 170: 1459-1472) teach the effect of amino acid substitution and/or mutation on the activity of the peptide (see Table 3, for example). There is not sufficient amount of examples provided to encompass the numerous characteristics of the whole genus claimed.
The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate"). Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
U.S.C. 102
10. 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.
11. 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.
12. Claim(s) 1-2 and 31 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Poyet et al (US 2017/0058010 or issued as US Patent No. 10358469).
13. Poyet et al teach a protein sequence that is 100% identical to instant SEQ ID NO: 1 (see SEQ ID NO: 1). Poyet et al teach a pharmaceutical composition comprising the polypeptide and a pharmaceutically acceptable carrier (see for example, paragraphs [0209]-[0213] of US 2017/0058010). Since Poyet et al teach the protein sequence that is 100% identical to instant SEQ ID NO: 1 and a pharmaceutical composition comprising the peptide/protein and a pharmaceutically acceptable carrier, Poyet et al anticipates instant claims 1-2 and 31.
U.S.C. 103
14. 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.
15. 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.
16. 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.
17. 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.
18. Claim(s) 1-2, 6-7 and 31 is/are rejected under 35 U.S.C. 103 as being unpatentable over Poyet et al (US 2017/0058010 or issued as US Patent No. 10358469) in view of Veronese et al (Drug Discovery Today, 2005, 10(21): 1451-1458).
19. Poyet et al teach a protein sequence that is 100% identical to instant SEQ ID NO: 1 (see SEQ ID NO: 1). Poyet et al teach a pharmaceutical composition comprising the polypeptide and a pharmaceutically acceptable carrier (see for example, paragraphs [0209]-[0213] of US 2017/0058010). Since Poyet et al teach the protein sequence that is 100% identical to instant SEQ ID NO: 1 and a pharmaceutical composition comprising the peptide/protein and a pharmaceutically acceptable carrier, Poyet et al anticipates instant claims 1-2 and 31.
The difference between the reference and the instant claims is that the reference does not teach that the API5 protein is fused to and/or chemically conjugated to one or more heterologous moieties, such as PEG polymer.
20. However, Veronese et al teach that “PEGylation defines the modification of a protein, peptide or non-peptide molecule by the linking of one or more polyethylene glycol (PEG) chains. This polymer is non-toxic, non-immunogenic, non-antigenic, highly soluble in water and FDA approved. The PEG-drug conjugates have several advantages: a prolonged residence in body, a decreased degradation by metabolic enzymes and a reduction or elimination of protein immunogenicity” (see abstract).
21. Therefore, it would have been obvious to one of ordinary skill in the art to combine the teachings of Poyet et al and Veronese et al to produce a PEG conjugated proteins. One of ordinary skill in the art would be motivated to combine with a reasonable expectation since Veronese et al teach the benefits of attaching at PEG moiety to a protein: polymer is non-toxic, non-immunogenic, non-antigenic, highly soluble in water and FDA approved, and the PEG-drug conjugates have a prolonged residence in body, a decreased degradation by metabolic enzymes and a reduction or elimination of protein immunogenicity. Therefore, the combined art is prima facie obvious over instant claims 1-2, 6-7 and 31.
22. Claim(s) 1-2, 6-8 and 31 is/are rejected under 35 U.S.C. 103 as being unpatentable over Poyet et al (US 2017/0058010 or issued as US Patent No. 10358469) in view of Marvelgent biosciences (PolyHis tag: how length matters in protein purification | MarvoBlog – Marvelgent Biosciences, January 29, 2018, pp. 1-8).
23. The teachings of Poyet et al is described above. The difference between the reference and instant claims is that the reference does not teach an affinity tag, and the elected species His-Tag.
24. However, Marvelgent biosciences teaches that greater number of histidine residues results in higher binding affinity, and is effective in purification of various target proteins.
25. Therefore, it would have been obvious to one of ordinary skill in the art to combine the teachings of Poyet et al and Marvelgent biosciences to attach a His-tag to the protein since it is well known in the art in the purification, that a His-tag is effective. Additionally, Marvelgent biosciences teaches that greater number of histidine residues results in higher binding affinity. One of ordinary skill in the art would be motivated to combine with a reasonable expectation of success, since proteins are conjugated to His-tags for high purification purposes. Therefore, the combined art is prima facie obvious over instant claims 1-2, 6-8 and 31.
CONCLUSION
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JULIE HA whose telephone number is (571)272-5982. The examiner can normally be reached Monday-Thursday 5:00 am- 6:30 pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, LIANKO GARYU can be reached at 571-270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JULIE HA/Primary Examiner, Art Unit 1654
6/16/2026
Prosecution Insights