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 with traverse of Group I (Claims 1-5, and 9-10) in the reply filed on 04/22/2026 is acknowledged. The traversal is based on applicant’s amendment to remove the term “oligomeric” from the current claims followed by inserting the term “IgM or IgM-type” anti-insulin antibody. Thus applicants argue there is no longer support for the examiner’s reliance on of Ikematsu et al. because Ikematsu et al. only teaches anti-insulin IgG autoantibodies and therefore unity of invention is retained. This is not found persuasive because prior to the examiner’s lack of unity based on “oligomeric” IgM anti-insulin antibodies, the written opinion of the international searching authority already held that there was lack of unity based on the IgM isotype and that these antibodies were well known in the state of the art (documents D1 to D4). For example:
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Thus, an IgM or IgM-type anti-insulin antibody that is monospecific for insulin was known and unity of invention is not retained. Further, Groups I and II (a priori) were drawn to multiple products (IgM antibodies and nucleic acids) which is not one of the categories of inventions provided in 37 CFR 1.475(b), and thus unity was lacking.
Upon review and reconsideration, the requirement for a species election has been withdrawn.
The requirement is still deemed proper and is therefore made FINAL.
Claim Status
Claims 1-10, 13-14, and 17-24 are currently pending.
Claims 6-8, 13-14, and 17-24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-5, and 9-10 are currently pending and under consideration.
Specification
The disclosure is objected to because of the following informalities: The brief description of the drawings has several references to colored items. For example, the specification teaches:
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Also see descriptions of Figure 3 and Figure 22.
Thus, it appears that some of applicants’ drawings may need to be submitted in color to distinguish these details. Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d). Applicants are reminded that color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification: Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Drawings
Figure 3b is objected to for recitation of amino acid sequences in the absence of corresponding sequence identifiers. See 37 CFR 1.821(c). 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.
Claim Objections
Claim 9 is objected to because of the following informalities: Claim 9 also claims pharmaceutical compositions comprising polynucleotides and host cells which are drawn to non-elected subject matter. Appropriate correction is requested.
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 1-5 and 9-10 are rejected for reciting “IgM or IgM-type” anti-insulin antibody 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. Specifically, it’s not clear how to interpret the metes and bounds of an “IgM type” anti-insulin antibody. The claims are set forth in the alternative, thus one can choose between an IgM antibody or an IgM-type antibody. However, what is the structural difference between an “IgM type” antibody compared to an IgM antibody? While the specification teaches [0089] that the term “IgM” has its general meaning in the art and refers to an immunoglobulin that possesses heavy m-chains, the specification does not appear to discuss what encompasses an IgM-type antibody and/or distinguish between an IgM and an IgM-type antibody. As written, it’s not clear how to distinguish between the two options.
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 2 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. Specifically, it’s not clear how claim 2 specifies a further limitation of Claim 1 because Claim 1 already sets forth that the antibodies are of the IgM isotype. 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.
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 1-3, 9-10 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.
The claims are broadly drawn to IgM anti-insulin antibodies that are monospecific for insulin and/or proinsulin OR IgM anti-insulin antibodies that have an affinity to insulin and/or proinsulin of Kd less than 5 x 10-7. However, disclosure of an antigen fully characterized by its structure, formula, chemical name, physical properties, or deposit in a public depository does not, without more, provide an adequate written description of an antibody claimed by its binding affinity to that antigen, even when preparation of such an antibody is routine and conventional. See Amgen Inc. v. Sanofi, 872 F.3d 1367, 1378, 124 USPQ2d 1354, 1361 (Fed. Cir. 2017)("knowledge of the chemical structure of an antigen [does not give] the required kind of structure-identifying information about the corresponding antibodies"); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1351-52, 97 USPQ2d 1870, 1877 (Fed. Cir. 2011) (patent disclosed the antigen the claimed antibody was supposed to bind, but did not disclose any antibodies with the specific claimed properties). See also MPEP 2163.II.A.3(a).
It is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin.
The fact that not just one CDR is essential for antigen binding or maintaining the conformation of the antigen binding site, is underscored by Casset et al. ("A peptide mimetic of an anti-CD4 monoclonal antibody by rational design", Biochemical and Biophysical Research Communications, Vol. 307, pg. 198-205. 2003) which constructed a peptide mimetic of an anti CD4 monoclonal antibody binding site by rational design and the peptide was designed with 27 residues formed by residues from 5 CDRs (Abstract). Casset et al. also states that although CDR H3 is at the center of most if not all antigen interactions, clearly other CDRs play an important role in the recognition process (page 199, left col.) and this is demonstrated in this work by using all CDRs except L2 and additionally using a framework residue located just before the H3 (see page 202, left col.). Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function. Rudikoff et al. ("Single amino acid substitution altering antigen-binding specificity"; Proceedings of the National Academies of Sciences, Vol. 79, pg. 1979-1983. March 1982) teaches that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function (Abstract).
The references demonstrate that an antibody must comprise all 6 CDRs in order to maintain the antigen binding specificity and affinity which is characteristic of the immunoglobulin. The instant claims fail to meet the requirements for disclosure because the antibody is described solely by the antigen to which it binds or by the affinity of the antibody to its antigen. Therefore, absent the defined CDRs of Claim 4 or the VH and VL chain sequences of claim 5 which are not rejected, the rejected claim(s) only define the anti-insulin or anti-proinsulin antibodies by their affinity for antigen or by the antigen it binds to which (as set forth above) would not reasonably convey to one skilled in the relevant art that the inventors at the time the application was filed, had possession of the claimed invention.
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 1-3, and 9-10 are rejected under 35 U.S.C. 101 because the claimed invention is directed to natural products without significantly more. Specifically, claims 1-3 appear to encompass naturally occurring and/or human IgM anti-insulin antibodies monospecific for insulin. For example, Sanz et al. (Jnl. of Immunol., Vol. 142, 1989, Applicant’s IDS) teach the isolation of Ab2022 which is of the IgM isotype and monospecific for insulin (Table 1, page 4055). Sanz et al. teach that Ab2022 is from a type I diabetic patient treated with heterologous insulin (page 4054, 2nd column). Further, Thomas, J. (Jnl. of Immunol., Vol. 150, 1993, Applicant’s IDS) taught the sequences of five monospecific IgM antibodies from an insulin-dependent diabetes mellitus patient. These antibodies are not polyreactive and their avidity profiles indicate that they bind human insulin comparably to circulating antibodies (page 1376, right column, paragraph 2, also Figures 1-5). Thus, the claimed antibodies do not sufficiently distinguish over IgM anti-insulin antibodies as they exist naturally because the claims do not particularly point out any non-naturally occurring differences between the claimed products and the naturally occurring products. When a law of nature or natural phenomenon is claimed as a physical product, the courts have often referred to the exception as a "product of nature". For example, the isolated DNA of Myriad and the primers of Ambry Genetics were described as products of nature by the courts. Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 580, 106 USPQ2d 1972, 1975 (2013); University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 758-59, 113 USPQ2d 1241, 1243 (Fed. Cir. 2014). As explained in those decisions, products of nature are considered to be an exception because they tie up the use of naturally occurring things, but they have been labeled as both laws of nature and natural phenomena. See MPEP 2106.04(b).
Further, the human intervention required by the claims (Claims 9-10) is limited to isolating the natural antibody products into a pharmaceutical composition with “a pharmaceutically acceptable carrier” and with a generic “therapeutic agent” (Claim 10). However, these additional elements do not add more than insignificant extra-solution activity to the judicial exception. As explained by the Supreme Court, the addition of insignificant extra-solution activity does not amount to an inventive concept, particularly when the activity is well-understood or conventional. Parker v. Flook, 437 U.S. 584, 588-89, 198 USPQ 193, 196 (1978). See MPEP 2106.05(g). Thus, the inclusion of such pharmaceutical carriers or other therapeutic agents does not add a meaningful limitation on the naturally occurring anti-insulin antibodies because it overlaps with what is well-understood, routine and conventional in the art. For example, one of ordinary skill in the art may use the antibodies as reagents to detect human insulin.
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.
Claim(s) 1-3 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Thomas, J. (Jnl. of Immunol., Vol. 150, No 4, 1993, IDS).
Thomas, J. teaches the sequences of five monospecific IgM antibodies from an insulin-dependent diabetes mellitus patient. These antibodies are not polyreactive and their avidity profiles indicate that they bind human insulin comparably to circulating antibodies (page 1376, right column, paragraph 2, also Figures 1-5).
Claim(s) 1-3 and 9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Livneh et al., Diabetes,35(1), December 1986, IDS).
Livneh et al. teach a monoclonal IgM antibody specific for human insulin isolated from a human patient with insulin-dependent diabetes mellitus (abstract, page 72, 2nd column). Figure 4 shows the estimation of binding affinity- solutions, each containing 2.5 ug of the purified monoclonal antibody and other reagents were dissolved in phosphate buffered saline (PBS) which encompasses a pharmaceutical composition of the anti-insulin antibody with a pharmaceutically acceptable carrier.
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.
Claim 1-5, 9-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim Claims 21, 23-24, 29-30 of copending Application No. 18/274605 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims cover/overlap the same products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Application No. 18/274605 claims a “protective-regulative” antibody, variant or fragment that comprises the same CDRs (Claim 23) and VH/VL chains (Claim 24) as the currently claimed CDRs and VH/VL chains of Claims 4-5. Further, the copending claims are inclusive of pharmaceutical compositions comprising a monospecifc anti-insulin antibody with “further therapeutic agents”. While the co-pending claims do not specifically define the isotype of the “protective-regulative” antibody, the specification teaches [0172] that typical antibody Ig variants discussed in context of the invention comprise IgG, IgM, IgE, IgA, or IgD antibodies and that [0186] the composition of the invention can be used to in a method to modulate an immune response to a target antigen mediated by IgM. The portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of that claim. In particular, when ascertaining the scope of the reference’s claim(s) to a compound, the examiner should consider the reference’s specification, including all of the compound’s uses that are disclosed. See Sun Pharm. Indus., 611 F.3d at 1386-88, 95 USPQ2d at 1801-02.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GARY B NICKOL, Ph.D. whose telephone number is (571)272-0835. The examiner can normally be reached M-F 9AM-5:30PM.
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, Julie Wu can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/GARY B NICKOL/Primary Examiner, Art Unit 1643
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