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 .
Claim Status
Claims 1-16 are currently pending.
Election/Restrictions
Applicant’s election without traverse of Group I and the species of antibody comprising CDRs from SEQ ID NO:13 and 14 in the reply filed on 19 November 2025 is acknowledged. The antibody which corresponds to these heavy/light chain amino acid sequences is called P8B according to the instant specification.
Claims 8-10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 19 November 2025.
Information Disclosure Statement
The listing of references in the specification 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.
The information disclosure statement (IDS) submitted on 20 July 2022 has been considered by the examiner.
Drawings
The drawings are objected to because they do not comply with 37 CFR 1.84(a), (l) and (p).
1.84 Standards for drawings.
(a) Drawings. There are two acceptable categories for presenting drawings in utility and design patent applications.
(1) Black ink. Black and white drawings are normally required. India ink, or its equivalent that secures solid black lines, must be used for drawings;
(l) Character of lines, numbers, and letters. All drawings must be made by a process which will give them satisfactory reproduction characteristics. Every line, number, and letter must be durable, clean, black (except for color drawings), sufficiently dense and dark, and uniformly thick and well-defined. The weight of all lines and letters must be heavy enough to permit adequate reproduction. This requirement applies to all lines however fine, to shading, and to lines representing cut surfaces in sectional views. Lines and strokes of different thicknesses may be used in the same drawing where different thicknesses have a different meaning.
(p) Numbers, letters, and reference characters.
(1) Reference characters (numerals are preferred), sheet numbers, and view numbers must be plain and legible, and must not be used in association with brackets or inverted commas, or enclosed within outlines, e.g., encircled. They must be oriented in the same direction as the view so as to avoid having to rotate the sheet. Reference characters should be arranged to follow the profile of the object depicted.
(2) The English alphabet must be used for letters, except where another alphabet is customarily used, such as the Greek alphabet to indicate angles, wavelengths, and mathematical formulas.
(3) Numbers, letters, and reference characters must measure at least .32 cm. (1/8 inch) in height. They should not be placed in the drawing so as to interfere with its comprehension. Therefore, they should not cross or mingle with the lines. They should not be placed upon hatched or shaded surfaces. When necessary, such as indicating a surface or cross section, a reference character may be underlined and a blank space may be left in the hatching or shading where the character occurs so that it appears distinct.
Below is a screenshot of Figure 4, which is an example of the issues which are characteristic of all the drawings.
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It is also noted that the units which are recited in Figure 8 are not standard. The figure has “ug/mL” which is not an actual unit. The figure might have intended micrograms per milliliter; therefore “µg/mL” should have been used.
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
Applicant’s submission of the substitute specification to update the Sequence Listing incorporation statement filed 11 July 2025 has been received and entered. The information in the incorporation statement is correct, however, it is noted that the terminology of “approximately” was used when referencing the size of the sequence listing file. This file size is a precise measure and therefore, use of “approximately” is not encouraged when stating the file size. “Approximately” should be deleted from this paragraph.
Specification
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. The claims are not directed to uses of the antibody and therefore should not be included in the title.
The title is also objected to for the use of the acronym “ANGPTL3”. It is suggested that the full name of the protein be used (angiopoietin-like 3) in the title and at the first appearance in the abstract, specification and claims. The abbreviation can be included in the abstract, specification and claims along with its first usage and then the abbreviation can be used anytime subsequently. This provides better clarity for understanding the instant application and avoids any confusion with similar acronyms which may appear in the art.
The disclosure is objected to because of the following informalities:
The citation of “J. biol. Chem, 243, p3558 (1968)” at [0027] is not sufficient to retrieve the journal article to which specification is referring. Additional information is necessary and the citation should be updated accordingly.
The citation of “Roovers et al. (2001), Cancer Immunol” at [0044] is incomplete and therefore, the journal article which is being cited is unclear. Additional information is required and the citation should be updated accordingly.
The citation of “Protein Engineering, 7, 697 (1994)” at [0048] is incomplete and should be corrected.
The citation of “immunoglobulin journal 20011ISBN012441351” at [0060] is not sufficient to access the material to which the specification is referring. Correction of the citation such that the material that is being referenced can be obtained is required.
Paragraph [0148] is single spaced while the rest of the specification is double spaced. It is suggested that this paragraph also be double spaced unless there is some reason for the distinction.
The use of the term “FMAT™ 8100 HTS” system (see [0080]), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
The use of the term “PHERAstar®” (see [0129]), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
The use of the term “Flexstation®3” (see [0131]), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
The use of the term “GRAPHPAD PRISM®” (see [0131]), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
The use of the term “ADVIA®” (see [0135], [0138], [0140], [0145]), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Appropriate correction is required.
Claim Objections
Claim 1 is objected to because of the following informalities: the claim recites the acronym “ANGPTL3” without any explanation as to the meaning. Because the art to which the invention pertains can often include multiple acronyms for the same product or where the same acronym can be attributed to multiple products, it is routine to spell out the meaning of the acronym at the first usage. Appropriate correction is required.
Claim 1 is objected to because of the following informalities: claim 1 recites “identical in sequences to those of a heavy chain” and “identical in sequence to those of a light chain”. These recitations are grammatically cumbersome. The following language is suggested for clarity purposes:
i) the heavy chain variable region has an HCDR1, an HCDR2 and an HCDR3 amino acid sequence identical to those of the heavy chain variable region set forth in SEQ ID NO: 13, and the light chain variable region has an LCDR1, an LCDR2 and an LCDR3 amino acid sequence identical to those of the light chain variable region set forth in SEQ ID NO: 14.
Claims 2, 4 and 5 are objected to because of the following informalities: claims 2, 4 and 5 all refer to “having a sequence”; it is suggested that this recitation be amended to “having an amino acid sequence”.
Claim 4 is objected to because of the following informalities: claim 4 recites “shown below” in line 2. However, the claim does not “show” the heavy/light chain variable regions as alleged. The claim could be reworded as follows:
…according to claim 3, comprising a heavy chain variable region and a light chain variable region, wherein:
(D) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:13 and the light chain variable region comprises the amino acid sequence of SEQ ID NO:14;
(E) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:11 and the light chain variable region comprises the amino acid sequence of SEQ ID NO:12; or
(F) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:9 and the light chain variable region comprises the amino acid sequence of SEQ ID NO:10.
Claim 7 is objected to because of the following informalities: claim 7 recites heavy chain/light chain “as set forth in SEQ ID NO:”. The actual heavy/light chain is not set forth in a sequence identifier, but rather, the amino acid sequence of the heavy/light chain is set forth in the identifier. It is suggested that the claim be amended to recite “amino acid sequence as set forth in”.
Claim 11 is objected to because of the following informalities: claim 11 depends from claim 1 and claim 9, however, claim 9 is directed to a non-elected invention. Claim 11 should be amended to remove the dependency to the non-elected invention (note: the invention of claim 9 is not subject to rejoinder). Appropriate correction is required.
Appropriate correction is required.
Improper Markush
Claims 1-4 and 6-7 are rejected on the basis that it contains an improper Markush grouping of alternatives. Claims 5, 11 and 13 do not recite the improper Markush, but depend from claim 1 and therefore include the improper Markush grouping and are also rejected for this reason (as they do not obviate the issue necessitating the rejection). 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 anti-ANGPTL3 antibodies 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: the alternatives do not share both a substantial structural feature and a common use that flows from the substantial structural feature.
The specification discloses 3 anti-ANGPTL3 antibodies which are named P3, P8 and P8B. P8 and P8B are proper species of one another as the two antibodies share a substantial structural feature as the two antibodies only differ by a total of 2 amino acids in the CDR regions which are the structural feature that provides for the binding affinity of the antibodies. Below is an alignment of the heavy and light chain variable regions of P3 and P8B.
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The CDR regions for P8B are at positions 31-35, 50-66 and 99-113 relative to SEQ ID NO:13 (heavy chain) and positions 24-39, 55-61 and 94-102 relative to SEQ ID NO:14 (light chain). As can be seen in the alignments above, the regions which are responsible for binding do not share a significant structural similarity. Therefore, P3 and P8B are not proper species of one another and the Markush grouping is improper. Element (iii) of claim 1 corresponds to P3 as does (vi) of claim 2, (C) of claim 3, (F) of claim 4, (I) of claim 6, and (L) of claim 7.
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 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 5 and 11 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.
Claim 5 recites “preferably” in line 4 and “more preferably” in line 7. Regarding claim 5, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention.
Claim 11 recites “a therapeutically effective amount”. However, as the claim is directed to a pharmaceutical composition and no recited method or intended therapeutic application, the metes and bounds of “therapeutically effective amount” are unclear and indefinite. As there is no stated function which is to be achieved and because ANGPTL4 is implicated in numerous biological functions (blood vessel formation, wound healing, cancer progression, fatty acid uptake, lipid storage), the amount which would be “therapeutic” would depend on the effect to be achieved. This rejection could be avoided by deletion of the recitation “therapeutically effective amount”.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 13 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 13 is directed to a kit which comprises the anti-ANGPTL3 antibody or antigen-binding fragment thereof according to claim1. The recitation of “kit” could be interpreted as an intended use and therefore, does not further limit the subject matter of claim 1 (directed to the antibody/antigen-binding fragment). Claim 13 could also be interpreted as a composition but the only component which is recited for the composition is the antibody/antigen-binding fragment of claim 1. Therefore, claim 13 does not further limit the subject matter of the claim from which it depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-7 and 11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of copending Application No. 18/580,328 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims to an antibody or antigen binding fragment thereof which binds angiopoietin-like 4 would be obvious over pharmaceutical compositions which comprise the same antibody. The CDR amino acid sequences of the antibody of the instant application are identical to those of ‘328 as are the heavy/light chain variable chains and the heavy/light chains, therefore, the anti-ANGPTL3 antibody of the instant claims is identical to that of the anti-ANGPTL3 antibody in the pharmaceutical composition claims of ‘328. Therefore, the claims are not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Citation of Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. WO2012/174178 A1: discloses anti-ANGPTL3 antibodies. However, while anti-ANGPTL3 antibodies are disclosed, the reference does not disclose an antibody which has the same amino acid sequence structure (CDRs and heavy/light chains) as the anti-ANGPTL3 antibody of the instant claims.
Allowable Subject Matter
No claims are currently allowable. However, an anti-angiopoietin-like 3 antibody of embodiment (i) or embodiment (ii) of claim 1 are free of the prior art of record. Additionally, antibodies P8B and P8 are proper species of one another, therefore, the species election with regard to these two species is withdrawn. Claims limited to these two embodiments (antibodies P8B and P8) are free of the prior art of record. Embodiment (iii) of claim 1 is not a proper species (see improper Markush rejection above) and therefore, it has not been searched or examined.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Christine J Saoud whose telephone number is (571)272-0891. The examiner can normally be reached M-F, 8am-4pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, vanessa ford can be reached at 571-272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Christine J Saoud/Primary Examiner, Art Unit 1645
/VANESSA L. FORD/ Supervisory Patent Examiner, Art Unit 1674