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
Applicant’s election without traverse of Group I, claims 1-4, 8-12, 16 in the reply filed on 12/31/25 is acknowledged.
Claims 17, 19-28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/31/25.
Regarding the requirement for species election, which specifically stated to “specify its activity and all moieties that are fused or otherwise attached to it, if such applies,” page 4 of 11/3/25 Restriction Requirement, Applicant’s election without traverse of “SEQ ID NO:12, an isolated polypeptide that is alarmin and cell-penetrating” in the reply filed on 12/31/25 is acknowledged.
Claims 10-12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/31/25. Each of claim 10’s three sequences differ from the elected SEQ ID NO:12, and claims 11 and 12 are directed to fusion peptides, not elected.
The elected species, SEQ ID NO:12, a polypeptide sequence having 37 amino acids, was found free of the art.
Given that the claims recite a plurality of alternatively usable substances or members, which may include independent and distinct inventions, and that the examiner has determined that the elected species is allowable over the prior art, the examination is extended to a non-elected species that falls within the scope of a proper Markush grouping that includes the elected species (The examiner need not extend the search to any additional species that do not share a single structural similarity and a common use with the elected species, see MPEP 803.01 A and C.2.).
The non-elected species is the polypeptide identified by SEQ ID NO:21 in US 20040002457 A1, published 1/1/2004. A comparison with instant SEQ ID NO:12 is as follows:
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852
819
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Based on the essentially identical similarity (one difference) across all of instant SEQ ID NO:12’s 37 amino acids, and the presence of glycine, arginine and phenylalanine amino acid motifs to the N- terminus of the ‘457’s SEQ ID NO:21 that are found in instant SEQ ID NO:12, that is, Lys Gly Glu Gly Gly Phe Gly Gly Arg Gly Gly Gly Arg, KGEGGFGGRGGGR, from 1 to 13 of the 457’s SEQ ID NO:21, the examiner concludes that this non-elected species falls within the scope of a proper Markush grouping of claim 1 that includes the elected species, and possesses at least one of alarmin and/or cell penetrating activity.
Claim Status
Claims 1-4, 8-12, 16, 17, and 19-28 are pending.
Claims 5-7, 13-15, 18 are cancelled.
Claims 17, 19-28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/31/25.
Claims 10-12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/31/25.
Claims 1-4, 8, 9 and 16 are pending and under examination.
Claims 1-4, 8, 9 and 16 are rejected.
Priority
The instant application, filed 01/13/2023 is a National Stage entry of PCT/SG2021/050405 , International Filing Date: 07/09/2021
claims foreign priority to 10202006656Q, filed 07/13/2020.
Information Disclosure Statement
The Examiner has considered the reference(s) provided in the 1/13/23, 4/28/25 and 10/22/25 Information Disclosure Statements, and provides a signed and dated copy of each herewith.
The listing of references in the specification, pages 44-47, is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper.” Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Drawings
The drawings are objected to because in Figure 24, page 31/33, no amino acid sequence is shown corresponding to “SEQ ID NO:12” at the bottom of the figure. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - Sequences appearing in the specification and claims are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c).
Required response – Applicant must provide: SEQ ID numbers for short peptide sequences that have at least four specifically defined amino acids, such as on page 4, line 16, page 16, line 13, and claims 2 and 3.
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specific deficiency - The incorporation by reference paragraph required by 37 CFR 1.834(c)(1), 1.835(a)(2), or 1.835(b)(2) is missing, defective or incomplete.
Required response - Applicant must:
• Provide a substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.831(a) and 1.831(b). However, this application fails to comply with the requirements of 37 CFR 1.831-1.834. The examiner has noted that sequence identifiers for short peptides falling under the rules are non-existent, and that a paragraph regarding the sequence listing is missing. Applicant must provide:
• A replacement “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2., as well as
• A statement that identifies the location of all additions, deletions, or replacements of sequence information in the “Sequence Listing XML” as required by 1.835(b)(3);
• A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.835(b)(4);
• A statement that the “Sequence Listing XML” includes no new matter in accordance with 1.835(b)(5); and
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(b)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
PLEASE ALSO NOTE – SEQ ID NUMBERS 1-3 ARE STATED IN THE SEQUENCE LISTING TO BE ARTIFICIAL SEQUENCES, HOWEVER IT IS THE EXAMINER’S UNDERSTANDING THAT THESE ARE THE SEQUENCES OF NATIVE PROTEINS. PLEASE CORRECT OR RESPOND TO EXPLAIN WHY THE <213> INDICATIONS FOR THESE SEQ ID NUMBERS ARE CORRECT.
Specification
The disclosure is objected to because of the following informalities: Several SEQ ID numbers are missing, see immediately above.
Appropriate correction is required.
Claim Interpretation
Following routine juxtaposition convention for modifying phrases, the claim 1 line 2 descriptive phrase “with alarmin and/or cell penetrating activity” is interpreted to refer to and modify the immediately preceding limitation “a glycine and arginine-rich (GAR/RGG) region.”
If applicant disagrees with such interpretation, this should be made of record in the next correspondence.
The transition phrase “comprising” is inclusive or open-ended and does not exclude additional, unrecited elements or method steps., see MPEP 2111.03 I. Therefore the claim 1 isolated polypeptide does not exclude additional, unrecited elements in addition of the “glycine and arginine-rich (GAR/RGG) region.”
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-4, 8, 9 and 16 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
First, claim 1 states the that isolated polypeptide comprises “a glycine and arginine-rich (GAR/RGG) region” further describing this, or the isolated polypeptide, to be “with alarmin and/or cell-penetrating activity.” While applicant may consider that those of ordinary skill in the art have identified this type of region, nonetheless there is no clear boundary that adequately provides metes and bounds for this region such that the claim’s boundaries are clear. Neither is there a definition in the application as filed, and also the significance of (GAR/RGG) is unclear – its seems the first part indicates “glycine and arginine” or “glycine arginine region”, rather than “glycine, alanine, arginine” whereas the second part appears to provide one possible trimer motif, if meaning to indicate single letter amino acids – arginine-glycine-glycine. If so, must the claimed region only have RGG motifs, must it have some minimum percentage of RGG motifs across the whole region (the whole region itself not clearly identified by sequence requirements)?
Also, as to function, although “alarmin and/or cell-penetrating activity” is interpreted broadly, so that any de minimis activity satisfies the requirement for either activity, the required structure(s)/motifs to achieve this/these function(s) are not set forth adequately to indicate what structure provides this/these function(s). This is an additional basis for a lack of clear metes and bounds of what is claimed, and consequent indefiniteness.
These bases of rejection apply to claim 1 and all dependent claims thereof.
Regarding the latter basis of rejection regarding function and the lack of structure required to achieve such, this basis separately and additionally applies to claims 2 and 3 because the minimum required sequence of the claimed regions comprising various ‘trimers’ and/or ‘tetramers’ to achieve the function(s) are not set forth, and to claim 4 as to fragment or mutant, and to claim 8 as to mutant.
Additionally:
Claim 2 recites the limitation "The isolated peptide" in line 1 and “the peptide” in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 3 depends from claim 2 and recites the limitation "The isolated polypeptide" in line 1 and then refers to “the peptide” in line 2. There is insufficient antecedent basis for this limitation in the claim, and as to the line 1 reference to the isolated polypeptide of claim 2, it is unclear whether this refers to the claim 2 isolated peptide or further back to the claim 1 isolated polypeptide, and as to the line 2 reference to “the peptide,” it is unclear whether this refers to the ‘isolated peptide’ of claim 2 or an ‘isolated polypeptide’ of claim 1.
Claims 4, 8-10 and 16 depend directly or indirectly from claim 1, not depending from claim 2, and in multiple places recite the limitation “the isolated peptide” or “the peptide.”
The conflicting uses of “polypeptide” and “peptide” are considered aggravated situations leading to confusion and lack of understanding of the metes and bounds of what is claimed because although a native protein such as nucleolin clearly is encompassed by “polypeptide”, it might arguably not be for “peptide,” and despite that upon a search by the examiner no distinctions were made in the application as filed, the examiner remains mindful of possible distinctions applicant might argue based on ordinary and customary meanings.
Correction is required.
Additionally, claim 8 recites the limitations "the peptide or mutant thereof" in lines 1-2. There is insufficient antecedent basis for the limitation “mutant” in the claim (and see above regarding “the peptide”).
Additionally, claim 16 part c) is confusing and unclear because there is no reference to any preceding claim following “at least one of the isolated peptide” (and see above regarding “peptide”).
Correction is required.
Claim Rejections - 35 USC § 112
Claims 2-4, 8 and 16 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 MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. 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 (Fed. Cir. 1997); In re Gostelli, 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. While all of the factors have been considered, a sufficient amount for a prima facie case under this section are discussed below.
Further, to provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include: a) the scope of the invention; b) actual reduction to practice; c) disclosure of drawings or structural chemical formulas; d) relevant identifying characteristics including complete structure, partial structure, physical and/or chemical properties, and structure/function correlation; e) method of making the claimed compounds; f) level of skill and knowledge in the art; and g) predictability in the art.
The importance of structure/function correlations has been highlighted by the courts (Abbvie Deutschland v. Janssen Biotech and Centorcor Biologics, App. No. 2013-1338, -1346 (Fed. Cir. , July 1, 2014)). The Abbvie case involved antibodies and written description. The court stated: “We have held that “a sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Id. at 1350 (quoting Eli Lilly, 119 F.3d at 1568– 69).”. The courts then further stated: “With the written description of a genus, however, merely drawing a fence around a perceived genus is not a description of the genus. One needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus.” (emphasis added) and then state: " Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Ariad, 598 F.3d at 1351 (“[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology.”); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1352 (Fed. Cir. 2011).
In the instant case, one could not visualize or recognize a sufficient number of species representative of the claimed genus with the property or properties as claimed.
First, claim 1 states no structural limitations for the isolated polypeptide nor the glycine and arginine-rich (GAR/RGG) region with alarmin and/or cell penetrating activity.
Second, given the open transition “comprising” in claim 1, when considering the range of possible unrecited sequences and structures of the isolated polypeptide of claim 1 in addition to the glycine and arginine-rich (GAR/RGG) region with alarmin and/or cell penetrating activity, claim 1 encompasses a huge genus of possible amino acid sequences attached to either or both of the N- and C-termini of the glycine and arginine-rich (GAR/RGG) region with alarmin and/or cell penetrating activity.
While applicant has demonstrated that several sequences comprising repeats of trimers and tetramers such as those listed in claims 2 and 3 provide polypeptides demonstrating one or both of alarmin and/or cell penetrating activity, these examples are very limited in their structural diversity and are not representative of the breadth of possible polypeptides of claim 1. Numerous diverse and diversely structured and diversely functioning amino acid sequences can be added to any of the evaluated and disclosed sequences, and still fall within the scope of claim 1 isolated polypeptide. Both the diversity and size range of the claim 1 isolated polypeptide are very large, and are not further limited by any of claims 2-4, 8 or 16. As to the size of proteins that could be part of or modified to be part of the claim 1 isolated polypeptide, Linke and Hamdani, Circulation Research, March 14, 2014, 1052-1068 teaches that the titan protein has 34350 amino acid residues, page 1053, so an isolated polypeptide encompassed by claim 1 can be at least this large. Based on Gotelli et al., Trends in Ecology and Evolution August 2012, Vol. 27, No. 8, pp 436-442, the number of diverse proteins is very large, page 438 and elsewhere. Given the diversity of possible amino acid sequences that are within the breadth of the claim and this size limit, the disclosed and taught species encompassed by claim 1 and other claims rejected under this section is very limited when considering the size and diversity of the genus of isolated polypeptides encompassed by these claims.
The small number of polypeptides taught and/or evaluated is clearly not representative of the claimed genus, and as such applicant was not in possession of claim 1’s subject matter in its entirety. A point that further supports this conclusion is that even though applicant has shown its limited polypeptides to have either or both of the claimed activities, applicant has not demonstrated this when a polypeptide comprising one such sequences also comprises a large, bulky heterologous amino acid sequence that through structure, charge or other factor(s) may impede or prevent such activity or activities. Please note that these functional limitations not have clearly defined and understood corresponding structural limitations in claim 1 that provide for it to be achieved, which also would limit the breadth of the claimed genus.
As stated supra, 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 that claims 1-4, 8 and 16 are broad and diverse with respect to all possible polypeptides encompassed by the claims. Moreover, the specification lacks sufficient variety of species to reflect this variance in the genus. While having written description of peptides identified in the specification, including examples, the specification does not provide sufficient descriptive support for the myriad of species embraced by the claims.
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 Appellant 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.
Accordingly, claim 1 is rejected under this section, as are claims 2-4, 8 and 161 for the same reasoning applied to claim 1.
Applicant may consider limiting the size or other structural limitation of the claimed isolated polypeptide that is supported by the application as filed.
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.
Claims 1-4, 8, 9 and 16 rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception, a natural protein2 (a product of nature natural product/natural phenomenon) without significantly more. The claim(s) recite(s) a natural phenomenon, an isolated polypeptide comprising a glycine and arginine-rich (GAR/RGG) region with alarmin and/or cell penetrating activity, this is not size-restricted and the protein nucleolin meets the claim 1 structural requirement of a glycine and arginine-rich region, as best understood, and also is known to have alarmin activity. This judicial exception is not integrated into a practical application because there are no additional elements in claims 1-4 and 8. Regarding claim 16, nucleolin in a cell meets the requirements of the composition of a) because a cell comprises multiple antigens to another species. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no additional elements in claims 1-4, 8 and 16 that result in a marked difference, or a markedly different composition as to claim 16. Regarding claim 9, given that SEQ ID Nos. 7 and 8 are subsequences of SEQ ID NO:1, nucleolin, and based on the data as understood by the examiner, there is no direct comparison of properties of the claim 9 SEQ ID Nos. 7 and 8 peptides with nucleolin, so no evidence of a markedly different characteristic.
As to the complete analysis:
Regarding Step 1, all claims rejected under this section are compositions of matter.
Regarding Step 2A Prong One, all claims rejected under this section recite a product of nature natural product/natural phenomenon, a naturally occurring protein.
Regarding Step 2A Prong One, claims 1-4, 8 and 9 rejected under this section do not recite additional elements that integrate the judicial exception into a practical application, and as to claim 9 there is no evidence of a markedly different characteristic at least of SEQ ID NO:7 or 8 which are portions of the C-terminus nucleolin protein. As to claim 16, part a), the additional presence of at least one antigen, also a natural product, would not reasonably result in a practical application, and this combination also would occur in cells, including cells during their destruction such as by apoptosis, and by this addition (of any antigen) there is no basis to conclude a markedly different characteristic of the polypeptide nor the composition.
Regarding Step 2B, claims 1-4, 8 and 9 rejected under this section do not recite additional elements that integrate the judicial exception into a practical application, and claim 16’s addition of an antigen also does not recite additional elements that integrate the judicial exception into a practical application, this because there is not a particular and specific practical application identifiable by the addition of any antigen in the claimed composition.
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.
(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.
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.
Claim(s) 1-4 and 8 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over US 20040002457 A1, published 1/1/2004.
Claim 1 is directed to an “isolated polypeptide comprising a glycine and arginine-rich (GAR/RGG) region with alarmin and/or cell penetrating activity.”
Claim 4, depending from claim 1, includes that the isolated ‘peptide’, interpreted here to mean the claim 1 isolated polypeptide, is the elected SEQ ID NO:12. Based on such dependency, SEQ ID NO:12 has alarmin and/or cell penetrating activity.
The ‘457 SEQ ID NO:1 is taught to be from the C-terminal portion of nucleolin, “and more specifically the last 63 amino acids of the C-terminal portion.” Abstract, this including per para 4, “the extreme C-terminal domain containing nine repeats of the tripeptide motif arginine-glycine-glycine (RGG domain).
As set forth above there is high similarity with instant SEQ ID NO:12, there being one additional glycine in the latter relative to the ‘457 SEQ ID NO:21 across SEQ ID NO:12’s 37 amino acid length.
The ‘457 SEQ ID NO:21 full sequence is:
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191
325
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The 13 amino acids to the N-terminus of the sequence portion that substantially (all but one glycine) corresponds with instant SEQ ID NO:12 are: KGEGGFGGRGGGR, which comprises two of the same amino acid trimers as the overlapping portion, and one amino acid tetramer, namely GGF GGR GGGR, these identified in instant claim 2 among claimed trimers and tetramers of the isolated polypeptide/peptide. The 50th amino acid, the only amino acid to the C-terminus of the sequence portion that substantially (all but one glycine) corresponds with instant SEQ ID NO:12 is G, glycine.
The ‘457 SEQ ID NO:1 falls within the broad genus of instant claim 1 as to comprising what is understood to comprise a glycine and arginine-rich region, (albeit this and “(GAR/RGG)” unclear per above). Given its similarity over its length with elected SEQ ID NO:12 and trimers and tetramers of instant dependent claims 2 and 3, and per MPEP 2112, given that the ‘457 SEQ ID NO:1 discloses all the limitations of a claim except a property or function, and the examiner cannot determine whether or not the reference inherently possesses properties which anticipate or render obvious the claimed invention, although here given the similarity the examiner strongly believes the ‘457 SEQ ID NO:1 would have at least de minimis both claimed activities, the examiner has basis for shifting the burden of proof to applicant as in In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980). See MPEP §§ 2112 - 2112.02.
Based on these considerations, the examiner rejects claims 1-4, 8 as anticipated by the ‘457 SEQ ID NO:1.
Regarding obviousness, based on the ‘457 SEQ ID NO:21 having substantial overlap with instant SEQ ID NO:12, and additionally comprising two of the same amino acid trimers and one of the same amino acid tetramer in SEQ ID NO:12 itself, and also recited in claim 2, the examiner concludes that based on close structural similarity, and the expectation that compounds similar in structure will have similar properties, see MPEP 2144.09, the ‘457 SEQ ID NO:21 has similar properties with instant SEQ ID NO:12, these properties including alarmin and/or cell penetrating activity.
Therefore the examiner rejects the following claims as obvious: claims 1 based on the above, claim 2 additionally because the ‘457 SEQ ID NO:21 comprises one or more of the recited trimers and tetramers, claim 3 based on being an alarmin-active or cell-penetrating fragment of nucleolin, SEQ ID NO:1, and claim 8 based on the similarity with instant SEQ ID NO:12 and the fact that per para 146 of the instant application instant SEQ ID NO:12 has both alarmin and cell penetrating activity (and note that any level of activity, including de minimis activity, meets the limitations of claim 8).
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.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over US 20040002457 A1, published 1/1/2004, as applied to claim 1 above, as evidenced by Wyatt et al., NATURE, VOL 393, pp 705-711, 18 JUNE 1998 (“Wyatt”).
Claim 16 is rejected as set forth above.
While the ‘457 specification teaches and suggests that nucleolin, and particularly the C-terminus section thereof that comprises more than five RGG repeats would be able to bind HIV, see para 20, and that nucleolin and the effective C-terminus portions of nucleolin (i.e., comprising more than five RGG repeats) bind or would bind HIV via the latter’s envelope glycoproteins, the gp120-gp41 complex, see paras 2, 3, 75, and FIG. 2 and description thereof, the ‘457 does not explicitly state that a peptide portion of the C-terminus 63 amino acids of nucleolin, such as its SEQ ID NO:21, is present with an antigen.
Instant SEQ ID NO:1, nucleolin, having 710 amino acids, compared to the ‘457 SEQ ID NO:21, indicates that SEQ ID NO:1 comprises 50 of the 63 C-terminus amino acids of nucleolin and 9 RGG trimers (not counting the C-terminus RGGG tetramer):
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The level of ordinary skill in the art is high.
One of ordinary skill in the art would reasonably consider that the ‘457 SEQ ID NO:21 would perform similarly to the entire C-terminus 63 amino acids when the performance were related to the presence of at least nine RGG trimers, based at least on para 20’s, “… synthetic peptides containing four or five RGG repeats were found not to bind HB-19A and moreover not affect HIV infection. Consequently, the nine RGG repeats in the nucleolin tail are required to generate a conformation that is optimum for HB-19A binding and inhibition of HIV infection.”
As to inhibiting HIV infection, the ‘457 per above teaches that HIV’s gp120-gp41 complex is involved in binding to nucleolin, but does not teach that this is an antigen.
As evidenced by Wyatt, HIV’s gp120-gp41 complex is an antigen, see Abstract and page 706.
Therefore based on these teachings and suggestions, one of ordinary skill in the art would reasonably conclude that when the ‘457’s SEQ ID NO:21 were combined in testing or in therapies against HIV infections, this peptide would be in a composition with at least one antigen. The rationale is that within the teachings of the ‘’457 one of ordinary skill in the art would have reasonably selected a peptide comprising at least nine RGG trimers of the C-terminus nucleolin protein to use for testing or therapy against HIV, the latter including the antigen gp120-gp41 complex, the ‘457’s SEQ ID NO:21 clearly known in the art in the ‘457, and that person of ordinary skill in the art could have substituted one known element for another, and the results of the substitution would have been predictable based on the substantial overlap with the full 63 amino acid C-terminus of nucleolin and SEQ ID NO:21 comprising at least nine RGG trimers.
Accordingly, claim 16 would have been obvious.
Art Made Of Record
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Zahariev et al., J. Peptide Sci, 11:17-28, 2005, cited in 10/22/25 IDS so copy not provided, and identified as D1 reference in the 12/19/24 European Partial Supplementary Search Report, also cited in 10/22/25 IDS so copy not provided, teaches 61 amino acid long peptides corresponding to the C-terminal region of human nucleolin, and are variously modified at the arginine side chain amine groups. This and other references in the 12/19/24 European Partial Supplementary Search Report were stated to be novelty destroying of the claims under consideration, however the above-applied US 20040002457 A1 SEQ ID NO:21 is considered closer to the instantly elected species.
Conclusion
No claim is allowed.
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/Joseph Fischer/
Examiner, Art Unit 1658
1 Claim 9 is not rejected assuming “isolated peptide” in each of lines 1 of claims 8 and 9 means “isolated polypeptide,” so refers back to the claim 1 isolated polypeptide.
2 For the sake of compact prosecution at least as to claim 1 the rejection is based on only one protein, notwithstanding that many proteins are known in the art that would meet the claim 1 (and other claim) limitations.