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 .
Status of the Claims
Claims 1-18 were originally filed August 23, 2022.
The amendment received October 30, 2022 canceled claims 1-18 and added new claims 19-29.
The amendment received April 19, 2026 and entered with the revival of the application approved June 11, 2026 amended claims 28 and 29 and added new claims 30-36.
Claims 19-36 are currently pending.
Claims 23-25, 27, 28, and 32-36 are currently under consideration.
Election/Restrictions
Applicant’s election without traverse of Group III (claims 23-36) in the reply filed on April 19, 2026 is acknowledged.
Claims 19-22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected product and a nonelected method, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on April 19, 2026.
Applicant’s election of inflammatory bowel disease (IBD), SEQ ID NO: 2 (Y27L mutation of SEQ ID NO: 1), intravenous administration, 2000 ng, and increasing the concentration of H+ in the cytoplasm of macrophages as the species in the reply filed on April 19, 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 26 and 29-31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species, there being no allowable generic or linking claim.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 April 19, 2026.
Please note: claim 26 is withdrawn because applicants did not elect the recited function, claim 29 is withdrawn because applicants did not elect a substitution, deletion, or addition to SEQ ID NO: 2, claim 30 is withdrawn because the cell preparation was not elected, and claim 31 is withdrawn because the cell preparation or the composition was not elected.
Priority
The present application is a 371 (National Stage) of PCT/CN2020/114587 filed September 10, 2020 which claims foreign priority to China 201910854478.3 filed September 10, 2019.
Applicant cannot rely upon the certified copy of the foreign priority application to overcome any rejection of record because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on March 3, 2022; December 19, 2023; and August 25, 2025 are being considered by the examiner.
Please note: only English language portions of the references were considered.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," 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 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) 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") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) 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 of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
See Figure 4.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, 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.
Specification
The disclosure is objected to because of the following informalities: the large gap between “SEQ ID NO.:” and “1” should be removed (see the paragraph spanning pages 25 and 26). In addition, the period should be removed (i.e. “SEQ ID NO.:” should read “SEQ ID NO:”). Please also refer to other instances of “SEQ ID NO.:” in the specification.
Appropriate correction is required.
The disclosure is objected to because of the following informalities: in withdrawn claim 25. “in the control group, in a control group” should read “in a control group”.
Appropriate correction is required.
The disclosure is objected to because of the following informalities: in withdrawn claim 26, “substances” should read “substance”.
Appropriate correction is required.
The disclosure is objected to because of the following informalities: in withdrawn claim 31, “1x104-5x107/ml” should read “1x104-5x107/ml”. See withdrawn claim 21. Please note: if this change is not made, the limitation will be considered new matter.
Appropriate correction is required.
The disclosure is objected to because of the following informalities: withdrawn claim 31 should refer to the cell preparation and not to the composition (i.e. lack of antecedent basis regarding “the phagocyte”).
Appropriate correction is required.
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
Claim 23 is objected to because of the following informalities: “inflammatory diseases” should read “inflammatory disease”. Appropriate correction is required.
Claim 23 is objected to because of the following informalities: “a non-IGF1R-binding substance or a cell preparation or a composition” should read “a non-IGF1R-binding substance, a cell preparation or a composition”. Appropriate correction is required.
Claim 23 is objected to because of the following informalities: a conjunction should be prior to the wherein clause. Appropriate correction is required.
Claim 23 is objected to because of the following informalities: it is unclear why “(a)” is utilized since there is no “(b)”, etc. Appropriate correction is required.
Claim 23 is objected to because of the following informalities: “in the control group, in a control group” should read “in a control group”. Appropriate correction is required.
Claim 23 is objected to because of the following informalities: the wherein clause should contain semicolons between each species in the Markush group (i.e. due to the commas present in some of the species). Appropriate correction is required.
Claim 23 is objected to because of the following informalities: “phenylalanine at position 26 is mutated to IGF2 mutant for Ser” should read “an IGF2 mutant where Phe at position 26 is mutated to Ser”. Appropriate correction is required.
Claim 27 is objected to because of the following informalities: “SEQ ID NO.:” should read “SEQ ID NO:”. Appropriate correction is required.
Claim 28 is objected to because of the following informalities: “SEQ ID NO.:” should read “SEQ ID NO:”. Appropriate correction is required.
Claim 32 is objected to because of the following informalities: “and remaining” should read “and the remaining”. See lines 5 and 10. Appropriate correction is required.
Sequence Interpretation
The Office interprets claims comprising SEQ ID NOs: in the following manner: “comprising a sequence of SEQ ID NO: 1” requires only a 2mer of SEQ ID NO: 1, “comprising the sequence of SEQ ID NO: 1” requires the full-length sequence with 100% identity to SEQ ID NO: 1 with any N-/C-terminal additions or any 5’/3’ additions, “consisting of SEQ ID NO: 1” requires the full-length sequence with 100% identity to SEQ ID NO: 1 and the same length as SEQ ID NO: 1, and “selected from the group consisting of SEQ ID NOs: 1, 2, and 3” requires the full-length sequence with 100% identity to SEQ ID NOs: 1, 2, or 3 and the same length as SEQ ID NOs: 1, 2, or 3. Any claim requiring a specific percent identity, necessarily requires at least the recited percent identity.
Present SEQ ID NOs: 1 and 2 are residues 25-91 of full length IGF2.
The Y27L mutation of present SEQ ID NO: 2 corresponds to Y51L of full length IGF2.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 23-25, 33, 35, and 36 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. This is a written description rejection.
With regard to the written description requirement, the attention of the Applicant is directed to The Court of Appeals for the Federal Circuit which held that 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.” University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1405 (1997), quoting Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993) (bracketed material in original) [The claims at issue in University of California v. Eli Lilly defined the invention by function of the claimed DNA (encoding insulin)] (the case is referred to herein as “Lilly”).
Additionally, it is noted that written description is legally distinct from enablement: “Although the two concepts are entwined, they are distinct and each is evaluated under separate legal criteria. The written description requirement, a question of fact, ensures that the inventor conveys to others that he or she had possession of the claimed invention; whereas, the enablement requirement, a question of law, ensures that the inventor conveys to others how to make and use the claimed invention.” See 1242 OG 169 (January 30, 2001) citing University of California v. Eli Lilly & Co.
Although directed to DNA compounds, this Eli Lilly holding would be deemed to be applicable to any compound or a generic of compounds; which requires a representative sample of compounds and/or a showing of sufficient identifying characteristics; to demonstrate possession of the compound or generic(s). In this regard, applicant is further referred to University of California v. Eli Lilly & Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997); “Guidelines for Examination of Patent Applications Under the 35 USC 112, first paragraph, ‘Written Description’ Requirement” published in 1242 OG 168-178 (January 30, 2001); and Univ. Of Rochester v G. D. Searle and Co. 249 F. Supp. 2d 216 (W.D.N.Y. 2003) affirmed by the CAFC on February 13, 2004 (03-1304) publication pending.
Additionally, Lilly sets forth a two part test for written description:
A description of a genus of cDNA’s may be achieved by means of a recitation of:
a representative number of cDNA’s, defined by nucleotide sequence, falling within the scope of the genus OR of a recitation of structural features common to the members of the genus.
See Regents of the University of California v. Eli Lilly & Co. 119 F.3d 1559 (Fed. Cir. 1997) at 1569.
Finally, University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404, 1405 held that:
...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.
Additionally, Cf. University of Rochester v G.D. Searle & Co., Inc., Monsanto Company, Pharmacia Corporation, and Pfizer Inc., No. 03-1304, 2004 WL 260813 (Fed. Cir., Feb. 13, 2004) held that:
Regardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to that subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.
In the present instance, the specification discloses only limited examples that are not representative of the claimed genus of “non-IGF1R-binding substance”, “a cell preparation” comprising a phagocyte treated with a non-IGF1R-binding substance, or “a composition” comprising a non-IGF1R-binding IGF2 mutant or inflammatory disease which can be treated with “non-IGF1R-binding substance”, “a cell preparation” comprising a phagocyte treated with a non-IGF1R-binding substance, or “a composition” comprising a non-IGF1R-binding IGF2 mutant; nor do the claims recite sufficient structural features which are common to members of the genus sufficient to demonstrate possession of the genus. The instant claims define the “non-IGF1R-binding substance” and “a cell preparation” comprising a phagocyte treated with a non-IGF1R-binding substance by the functional limitation of a non-IGF1R-binding substance. The claimed “non-IGF1R-binding substance” and “a cell preparation” comprising a phagocyte treated with a non-IGF1R-binding substance is only defined by functional properties (e.g. non-IGF1R-binding substance). The CAFC held that a functional definition is insufficient to adequately describe a product, therefore, an adequate written description not based on a functional definition is necessary.
The Examiner further notes the present claims stated by Applicant are broader in scope that those that were held to be impermissible in Lilly because, unlike Lilly, Applicants’ claims encompass a vast number of IGF2 mutants, a vector expressing an IGF2 mutant, and antibody, and/or a small molecule (see dependent claim 24). Here, the Applicant claims a method to prevent and/or treat an inflammatory disease via administering a “non-IGF1R-binding substance”, “a cell preparation” comprising a phagocyte treated with a non-IGF1R-binding substance, or “a composition” comprising a non-IGF1R-binding IGF2 mutant. The scope of these claims include a vast number of non-IGF1R-binding substances because the specification and claims do not place any limit on the number of components, the type of components, or how the components are combined. Furthermore, the specification and claims do not place any limit on the number of components, the types of components, or the manner in which the components might be connected to achieve preventing and/or treating inflammatory diseases. Moreover, the residues necessary for function and/or the mutations that retain the function of preventing and/or treating an inflammatory disease are not required by the present claims. Therefore, Applicants are using an inadequately described “non-IGF1R-binding substance”, “a cell preparation” comprising a phagocyte treated with a non-IGF1R-binding substance, or “a composition” comprising a non-IGF1R-binding IGF2 mutant to inadequately describe the claimed method. Consequently, there is no teaching that would allow a person of skill in the art to determine a priori that the Applicant was in possession of the full scope of the claimed invention at the time of filing because there is no common structural attributes that can link together all of the claimed “non-IGF1R-binding substance”, “a cell preparation” comprising a phagocyte treated with a non-IGF1R-binding substance, or “a composition” comprising a non-IGF1R-binding IGF2 mutant.
While the general knowledge and level of skill in the art for making IGF2 mutants, a vector expressing an IGF2 mutant, and antibody, and/or a small molecule and screening IGF2 mutants, a vector expressing an IGF2 mutant, an antibody, and/or a small molecule is high, this knowledge and level of skill does not supplement the omitted description because specific, not general, guidance is needed for the method of preventing and/or treating any inflammatory disease with a “non-IGF1R-binding substance”, “a cell preparation” comprising a phagocyte treated with a non-IGF1R-binding substance, or “a composition” comprising a non-IGF1R-binding IGF2 mutant. Since the disclosure fails to describe the common attributes or characteristics that identify all of the members of the genus or even a substantial portion thereof, and because the genus is vast and highly variant (e.g. non-IGF1R-binding substance, IGF2 mutant, antibody, and/or a small molecule), the limited examples in the specification (please refer to pages 4-7, 35) are insufficient to teach the entire genus. The specification teaches retinoic acid, profibriolysin, serglycin, GREG, sulfamidase, gusb, SEQ ID NO: 1 with a Y27L mutation (i.e. SEQ ID NO: 2), SEQ ID NO: 1 with Y27 mutations, SEQ ID NO: 1 with a F26 mutation, SEQ ID NO: 1 with a V43 mutation, SEQ ID NOs: 3-58 (without specifying how each sequence is mutated), and a number of inflammatory diseases without providing a correlation with IGF2. The only subject utilized in the specification is a mouse. It appears from the examples that only human IGF2 was utilized in mouse models of peritonitis (see Example 1) and IBD (see Example 5).
The specification discloses only limited examples that are not representative of the claimed genus of a “non-IGF1R-binding substance”, “a cell preparation” comprising a phagocyte treated with a non-IGF1R-binding substance, or “a composition” comprising a non-IGF1R-binding IGF2 mutant; nor do the claims recite sufficient structural features which are common to members of the genus sufficient to demonstrate possession of the genus. Therefore, the teachings in the specification are general teachings relating without guidance as to the individual components of the product. In addition, there are numerous “non-IGF1R-binding substance”, “a cell preparation” comprising a phagocyte treated with a non-IGF1R-binding substance, or “a composition” comprising a non-IGF1R-binding IGF2 mutant that could be employed in the invention with little direction or guidance for one of skill in the art to practice the claimed invention and which inflammatory disease would be treated. The expedient statements in the specification do not relate to an adequate disclosure or how to make and use the claimed invention. Consequently, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to adequately describe the vast genus. Thus, Applicant does not appear to be in possession of the claimed genus.
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 23, 25, 33, 35, and 36 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. One of skill in the art would not be able to determine the scope of the present claims. For example, it is unclear if the method of making the composition is required by the claims or not. In addition, the method is very convoluted and difficult to understand (e.g. same cell – does this mean the same cell type or the same cell is the test group and the control group – this would appear to defeat the purpose of the method and the control; what is the “unchanged or increased” in relation to, etc.).
Claims 23, 25, 33, 35, and 36 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. One of skill in the art would not be able to determine the scope of the present claims. For example, it is unclear why the wherein clause negates utilizing the preferred non-IGF1R-binding substances from the composition (e.g. IGF2 – only composition tested in the present application; see combinations thereof in relation to fragments 25-91 of WT IGF2 – SEQ ID NOs: 1 and 2, IGF2 with a Y27L mutation – SEQ ID NO: 2, IGF2 mutant with D-domain deletion).
Claim 28 is 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. One of skill in the art would not be able to determine the scope of the present claims. For example, it is unclear if the limitations in the parentheses are part of the claim limitations or not.
Claim 32 is 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. One of skill in the art would not be able to determine the scope of the present claims. For example, it is unclear if the limitations in the parentheses are part of the claim limitations or not.
Claim 36 is 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. One of skill in the art would not be able to determine the scope of the present claims. For example, it is unclear what structure is required for the function of “increases the concentration of H+ in the cytoplasm or macrophages” since only IGF2 (presumably SEQ ID NO: 1, but this is unclear also) was utilized in the specification (see Example 3).
Claim 24 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of an IGF2 mutant, a vector expressing an IGF2 mutant, an antibody, a small molecule, and combinations thereof is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: IGF2 mutant polypeptides, polynucleotides encoding IGF2 mutants in an expression vector, antibodies, and small molecules all have vastly different structures.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim 32 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of an IGF2 mutant, a vector expressing an IGF2 mutant, and combinations thereof is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: IGF2 mutant polypeptides and polynucleotides encoding IGF2 mutants in an expression vector have vastly different structures.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Please note: due to the plethora of objections and 35 USC 122 issues, applicants are respectfully requested to carefully review the entire specification and particularly the claims for any additional issues.
Claim Rejections - 35 USC § 102
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.
Claims 23, 25, 33, 35, and 36 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhang WO 97/35606 published October 2, 1997.
For present claims 23, 25, 33, 35, and 36, Zhang teaches methods of intravenously administering IGF-2 to a patient with IBD at doses of 0.1 mg/kg to 1000 mg/kg (please refer to the entire specification particularly the abstract; pages 2-5, 9, 13, 14; claims).
Therefore, the teachings of Zhang anticipate the presently claimed method.
Claims 23-25, 33, and 36 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Shi et al. CN-108114271-A published June 5, 2018; the corresponding international publication WO 2018/099363 published June 7, 2018 (translation provided); and the corresponding U.S. Patent Application Publication 2019/0381147 (utilized for the citations below; effective filing date of November 29, 2016 – by another; 35 USC 102(a)(2)).
For present claims 23-25, 33, and 36, Shi et al. teach methods of treating inflammatory bowel disease (IBD) via administering IGF2 and IGF2 active fragments including residues 25-91 SEQ ID NO: 2 (i.e. 100% identity and the same length as present SEQ ID NO: 1; same length as present SEQ ID NO: 2) at concentrations of 1 ng/ml-100 mg/ml and doses of 1 ng-1 mg/kg to a subject via injection and wherein 50 ng was administered to a mouse model of IBD (please refer to the entire specification particularly the abstract; paragraphs 1-47, 55, 56, 58, 61, 62, 64-66, 72, 74, 76, 144-152, 164-166, 190-194; Example 4, 5; claims).
Therefore, the present method is anticipated by the teachings of Shi et al.
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.
Claims 23-25, 27, 28, and 32-36 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang WO 97/35606 published October 2, 1997; Shi et al. CN-108114271-A published June 5, 2018; the corresponding international publication WO 2018/099363 published June 7, 2018 (translation provided); and the corresponding U.S. Patent Application Publication 2019/0381147 (utilized for the citations below; effective filing date of November 29, 2016 – by another) and Chettibi et al. U.S. Patent Application Publication 2008/0279765 published November 13, 2008.
For present claims 23-25, 27, 28, and 32-36, Zhang teaches methods of intravenously administering IGF-2 to a patient with IBD at doses of 0.1 mg/kg to 1000 mg/kg (please refer to the entire specification particularly the abstract; pages 2-5, 9, 13, 14; claims).
However, Zhang does not teach present SEQ ID NO: 1 or SEQ ID NO: 2.
For present claims 23-25, 27, 28, and 32-36, Shi et al. teach methods of treating inflammatory bowel disease (IBD) via administering IGF2 and IGF2 active fragments including residues 25-91 SEQ ID NO: 2 (i.e. 100% identity and the same length as present SEQ ID NO: 1; same length as present SEQ ID NO: 2) at concentrations of 1 ng/ml-100 mg/ml and doses of 1 ng-1 mg/kg to a subject via injection and wherein 50 ng was administered to a mouse model of IBD (please refer to the entire specification particularly the abstract; paragraphs 1-47, 55, 56, 58, 61, 62, 64-66, 72, 74, 76, 144-152, 164-166, 190-194; Example 4, 5; claims).
For present claims 23-25, 27, 28, and 32-36, Chettibi et al. teach methods of treating inflammation via administering to a patient and IGF2 fragment SEQ ID NO: 1 (i.e. 100% identity and the same length as present SEQ ID NO: 1) or IGF2 Tyr27Leu SEQ ID NO: 9 (i.e. 100% identity and the same length as present SEQ ID NO: 2) via intravenous injection (please refer to the entire specification particularly paragraphs 2, 32-34, 38-45, 158, 159, 176; claims). Chettibi et al. teaches that the IGF2 Tyr27Leu mutation SEQ ID NO: 9 diminishes affinity for IGF-1 receptor (see paragraph 39).
All the claimed elements (i.e. IGF2 of present SEQ ID NO: 1, IGF2 of present SEQ ID NO: 2 Y27L) were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions and the combination would have yielded predictable results (i.e. treatment of IBD with IGF2) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because the substitution of one known element (i.e. IGF2) for another (i.e. residues 25-91 of IGF2 – present SEQ ID NO: 1; residues 25-91 of IGF2 with a Y27L mutation – present SEQ ID NO: 2) would have yielded predictable results (i.e. treatment of IBD) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. utilizing IGF2 to treat IBD) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because a person of ordinary skill has good reason to pursue the known options within their technical grasp. If this leads to the anticipated success, it is likely the product no of innovation but of ordinary skill and common sense. See KSR International Co v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Claims 23-25, 27, 28, and 32-36 are rejected under 35 U.S.C. 103 as being unpatentable over Shi et al. CN-108114271-A published June 5, 2018; the corresponding international publication WO 2018/099363 published June 7, 2018 (translation provided); and the corresponding U.S. Patent Application Publication 2019/0381147 (utilized for the citations below; effective filing date of November 29, 2016 – by another) and Chettibi et al. U.S. Patent Application Publication 2008/0279765 published November 13, 2008.
For present claims 23-25, 27, 28, and 32-36, Shi et al. teach methods of treating inflammatory bowel disease (IBD) via administering IGF2 and IGF2 active fragments including residues 25-91 SEQ ID NO: 2 (i.e. 100% identity and the same length as present SEQ ID NO: 1; same length as present SEQ ID NO: 2) at concentrations of 1 ng/ml-100 mg/ml and doses of 1 ng-1 mg/kg to a subject via injection and wherein 50 ng was administered to a mouse model of IBD (please refer to the entire specification particularly the abstract; paragraphs 1-47, 55, 56, 58, 61, 62, 64-66, 72, 74, 76, 144-152, 164-166, 190-194; Example 4, 5; claims).
However, Shi et al. does not teach a Y27L mutation in present SEQ ID NO: 1 (i.e. present SEQ ID NO: 2).
For present claims 23-25, 27, 28, and 32-36, Chettibi et al. teach methods of treating inflammation via administering to a patient and IGF2 fragment SEQ ID NO: 1 (i.e. 100% identity and the same length as present SEQ ID NO: 1) or IGF2 Tyr27Leu SEQ ID NO: 9 (i.e. 100% identity and the same length as present SEQ ID NO: 2) via intravenous injection (please refer to the entire specification particularly paragraphs 2, 32-34, 38-45, 158, 159, 176; claims). Chettibi et al. teaches that the IGF2 Tyr27Leu mutation SEQ ID NO: 9 diminishes affinity for IGF-1 receptor (see paragraph 39).
All the claimed elements (i.e. IGF2 of present SEQ ID NO: 2 Y27L) were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions and the combination would have yielded predictable results (i.e. treatment of IBD with IGF2) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because the substitution of one known element (i.e. residues 25-91 of IGF2 – present SEQ ID NO: 1) for another (i.e. residues 25-91 of IGF2 with a Y27L mutation – present SEQ ID NO: 2) would have yielded predictable results (i.e. treatment of IBD) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. utilizing IGF2 to treat IBD) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because a person of ordinary skill has good reason to pursue the known options within their technical grasp. If this leads to the anticipated success, it is likely the product no of innovation but of ordinary skill and common sense. See KSR International Co v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 23-25, 33, and 36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 6 and 14-18 of copending Application No. 18/300,286 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both the present claims and the claims of copending Application No. 18/300,286 (reference application) are drawn to methods of administering present SEQ ID NO: 1 (residues 25-91 of IGF-2) to a subject with IBD.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Please note: a Notice of Allowance was mailed May 20, 2026.
Claims 23-25, 27, 28, and 32-36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 6 and 14-18 of copending Application No. 18/300,286 in view of Shi et al. CN-108114271-A published June 5, 2018; the corresponding international publication WO 2018/099363 published June 7, 2018 (translation provided); and the corresponding U.S. Patent Application Publication 2019/0381147 (utilized for the citations below; effective filing date of November 29, 2016 – by another) and Chettibi et al. U.S. Patent Application Publication 2008/0279765 published November 13, 2008.
Copending Application No. 18/300,286 (reference application) are drawn to methods of administering present SEQ ID NO: 1 (residues 25-91 of IGF-2) to a subject with IBD.
Shi et al. teach methods of treating inflammatory bowel disease (IBD) via administering IGF2 and IGF2 active fragments including residues 25-91 SEQ ID NO: 2 (i.e. 100% identity and the same length as present SEQ ID NO: 1; same length as present SEQ ID NO: 2) at concentrations of 1 ng/ml-100 mg/ml and doses of 1 ng-1 mg/kg to a subject via injection and wherein 50 ng was administered to a mouse model of IBD (please refer to the entire specification particularly the abstract; paragraphs 1-47, 55, 56, 58, 61, 62, 64-66, 72, 74, 76, 144-152, 164-166, 190-194; Example 4, 5; claims).
Chettibi et al. teach methods of treating inflammation via administering to a patient and IGF2 fragment SEQ ID NO: 1 (i.e. 100% identity and the same length as present SEQ ID NO: 1) or IGF2 Tyr27Leu SEQ ID NO: 9 (i.e. 100% identity and the same length as present SEQ ID NO: 2) via intravenous injection (please refer to the entire specification particularly paragraphs 2, 32-34, 38-45, 158, 159, 176; claims). Chettibi et al. teaches that the IGF2 Tyr27Leu mutation SEQ ID NO: 9 diminishes affinity for IGF-1 receptor (see paragraph 39).
All the claimed elements (i.e. IGF2 of present SEQ ID NO: 2 Y27L) were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions and the combination would have yielded predictable results (i.e. treatment of IBD with IGF2) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because the substitution of one known element (i.e. residues 25-91 of IGF2 – present SEQ ID NO: 1) for another (i.e. residues 25-91 of IGF2 with a Y27L mutation – present SEQ ID NO: 2) would have yielded predictable results (i.e. treatment of IBD) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. utilizing IGF2 to treat IBD) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because a person of ordinary skill has good reason to pursue the known options within their technical grasp. If this leads to the anticipated success, it is likely the product no of innovation but of ordinary skill and common sense. See KSR International Co v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
This is a provisional nonstatutory double patenting rejection.
Please note: a Notice of Allowance was mailed May 20, 2026.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
WO 97/25227
Future Communications
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMBER D STEELE whose telephone number is (571)272-5538. The examiner can normally be reached M-F 8-5.
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, Melissa Fisher can be reached at 571-270-7430. 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.
/AMBER D STEELE/Primary Examiner, Art Unit 1658
Prosecution Insights