Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
DETAILED ACTION
Status of Application, Amendments, and/or Claims
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 05/27/2026 has been entered. Claims 1, 3-9, 11-18, 23-27, and 93-97 are pending and currently under consideration.
Claim Rejections under 35 U.S.C. § 101
(i). 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.
(ii). Claims 1, 3-9, 11-18, 23-27, and 93-97 are rejected under 35 U.S.C. 101 because the claimed invention is not supported by either a specific and substantial asserted utility or a well-established utility.
Claims 1, 3-9, 11-18, 23-27, and 93-97 are drawn to a method for producing an antigen-binding molecule, comprising the following steps: (a) providing a polypeptide sequence of an antigen-binding molecule comprising an antigen- binding domain that comprises a heavy chain variable region and a light chain variable region,and an FcRn binding domain,(b) designing a modification of at least one amino acid position in the polypeptide sequence to form a sugar chain linking motif comprising the sequence Asn-X-Ser/Thr, wherein X is any amino acid residue other than proline, (c) preparing a gene encoding the antigen-binding molecule comprising the sugar chain linking motif designed in (b), (d) expressing the gene prepared in (c) in a host cell, (e) recovering the antigen-binding molecule expressed in (d), and (f) processing the antigen-binding molecule recovered in (e) with a neuraminidase and/or beta galactosidase so as to form a sugar chain linked to the sugar chain linking motif, wherein the sugar chain comprises a terminal galactose or terminal mannose. The claimed invention is not supported by either a specific and substantial asserted utility or a well-established utility. A specific and substantial utility is one that is particular to the subject matter claimed and that identifies a “real world” context of use for the claimed invention which does not require further research.
First, since the claims are directed to a specific method of use, the utility of the claims are limited to that use. Consequently, there is no "well-established" utility for the method (See REVISED INTERIM UTILITY GUIDELINES TRAINING MATERIALS, Example 12, http://www.uspto.gov/web/patents/guides.htm).
Secondly, the utility of the claimed method is determined based upon the utility of the product produced by the method. In the instant case, the product produced by the instant method is a sugar chain linked to the sugar chain linking motif (see claim 1, step (f)), wherein the sugar chain comprises a terminal galactose or terminal mannose, and wherein the sugar chain linking motif comprising the sequence Asn-X-Ser/Thr. There is no specific and substantial utility for the sugar chain linked to the sugar chain linking motif. Any uses of the sugar chain linked to the sugar chain linking motif are all considered research uses and are not a substantial utility. See, e.g., Brenner v. Manson, 383 U.S. 519, 148 USPQ 689 (Sup. Ct. 1966) wherein a research utility was not considered a "substantial utility." Clearly, further research would be required to identify a disease that can be treated with the recited molecules. See Brenner v. Manson, 383 U.S. 519, 148 USPQ 689 (Sup. Ct. 1966), noting that "a patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion."
In summary, the claimed method is not supported by a specific and substantial utility because the instant disclosure does not identify or reasonably confirm a "real world" context of use, for example, treatment of a particular disease. "Congress intended that no patent be granted on a chemical compound whose sole 'utility' consists of its potential role as an object of use-testing." Brenner v. Manson, 148 USPQ at 696.
(iii). Claims 1, 3-9, 11-18, 23-27, and 93-97 are also rejected under 35 U.S.C. 112, first paragraph. Specifically, since the claimed invention is not supported by either a specific and substantial asserted utility or a well established utility for the reasons set forth above, one skilled in the art clearly would not know how to use the claimed invention.
Claim Rejections under 35 USC § 112 (a)
(i). The following is a quotation of the first paragraph of 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.
(ii). Claims 1, 3-9, 11-18, 23-27, and 93-97 are rejected under 35 U.S.C. 112(a), 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 at the time the application was filed, had possession of the claimed invention.
MPEP §2163 II.A.3(a) ii) (page 2100-189) states, “The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A), above), reduction to drawings (see i)(B), above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C), above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406”. Adequate written description requires more than a mere statement that it is part of the invention are reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016 (Fed. Cir.1991).
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus."). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) ("[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated."). "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).
Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation." Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date." See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014) (Holding that claims to all human antibodies that bind IL-12 with a particular binding affinity rate constant (i.e., koff) were not adequately supported by a specification describing only a single type of human antibody having the claimed features because the disclosed antibody was not representative of other types of antibodies in the claimed genus, as demonstrated by the fact that other disclosed antibodies had different types of heavy and light chains, and shared only a 50% sequence similarity in their variable regions with the disclosed antibodies.). If a representative number of adequately described species are not disclosed for a genus, the claim to that genus must be rejected as lacking adequate written description under pre-AIA 35 U.S.C. 112, first paragraph.
In the instant case, the claims are drawn to a method for producing an antigen-binding molecule comprising a sugar chain linking motif comprising the sequence Asn-X-Ser/Thr, wherein at least one designed sugar chain linking motif is present at position 75-77 of the heavy chain variable region, position 18-20 of the light chain variable region, or position 20-22 of the light chain variable region, and wherein a sugar chain is linked to the sugar chain linking motif, and wherein the sugar chain comprises a terminal galactose or terminal mannose. The claims do not require that an antigen-binding molecule, an antigen-binding domain, or an FcRn binding domain possess any structural/functional features. The specification states that the antigen-binding molecules of the present invention has one or more binding domains to a sugar chain receptor. The binding domain to a sugar chain receptor is not particularly limited in type and number, as long as the antigen-binding molecule has a binding activity to the sugar chain receptor in a neutral pH range and as long as he binding activity to the sugar chain receptor in an acidic pH range is lower than the binding activity to the sugar chain receptor in the neutral pH range (page 156, paragraph [0205]). Thus, the claims encompass a method for producing a genus of antigen-binding molecules without any characteristic structural/functional features.
The specification discloses an antibody as an antigen-binding molecule (paragraph [0246] on page 191), in particular anti-human IL-6 receptor antibody (examples), and two pairs of sugar chain receptor binding domain and sugar chain receptor: a sugar chain receptor binding domain having N-linked sugar chain with a terminal galactose and an asialoglycoprotein receptor; a sugar chain receptor binding domain having N-linked sugar chain with a terminal mannose and a mannose receptor (pages 155 and 157). Example 2 discloses preparation of anti-human IL-6 receptor antibody being capable of binding in a pH-dependent manner and having a galactose-ended complex linked sugar chain introduced in a variable region. However, no other antigen-binding molecules are disclosed.
The specification does not describe a sufficient variety of species to reflect the variation within the genus. The instant disclosure of an antigen-binding molecule comprising an anti-human IL-6 receptor antibody is insufficient to support the broad genus of antigen-binding molecules. Moreover, the specification does not disclose a correlation of structure and function (for example, the properties recited in claims 3-9) of the genus of recited antigen-binding molecules. Furthermore, the prior art does not provide compensatory structural or correlative teachings sufficient to enable one of skill to identify what other antigen-binding molecules might be. One of skilled in the art cannot envision the structure of other antigen-binding molecule with recited properties.
Due to the breadth of the recited genus of antigen-binding molecules, one skilled in the art would not recognize from the disclosure that Applicant was in possession of the instantly claimed invention and thus the instantly claimed method of producing the genus of antigen-binding molecules.
(iii). Response to Applicant’s argument
Applicant traverses this rejection because the Office's analysis improperly applies written-description standards developed strictly for composition-of-matter claims to the present method-of-production claims. Applicant argues that the structural-genus principles do not govern method claims. Applicant argues that since a method of production is defined by a sequence of operational steps rather than a static physical structure, the structural variance of the resulting antigen-binding molecule does not alter or invalidate the reliably described steps of the claimed process itself. Applicant argues that the claimed method utilizes molecular biology techniques that are routine, conventional, and well-known in the art and that it is legally unnecessary for the specification to catalog every structural permutation of the resulting antibodies. Applicant argues that the specification provides specific embodiments and concrete examples that support the claimed method.
Applicant’s argument has been fully considered but is not deemed to be persuasive. "[T]he ‘essential goal’ of the description of the invention requirement is to clearly convey the information that an applicant [inventor] has invented the subject matter which is claimed." In re Barker, 559 F.2d 588, 592 n.4, 194 USPQ 470, 473 n.4 (CCPA 1977). Another objective is to convey to the public what the applicant claims as the invention. See Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1566, 43 USPQ2d 1398, 1404 (Fed. Cir. 1997), cert. denied, 523 U.S. 1089 (1998). To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
Whether a claim is drawn to a product or a method of making a product, a patent application must meet written description requirement under 35 U.S.C. 112(a). In the instant case, the claims are drawn to a method for producing an antigen-binding molecule comprising a sugar chain linking motif comprising the sequence Asn-X-Ser/Thr, wherein X is any amino acid residue other than proline, and wherein a sugar chain is linked to the sugar chain linking motif, and wherein the sugar chain comprises a terminal galactose or terminal mannose. The claims do not require that an antigen-binding molecule produced by the method, an antigen-binding domain, or an FcRn binding domain possess any structural/functional features. The specification states that the antigen-binding molecules of the present invention has one or more binding domains to a sugar chain receptor. The binding domain to a sugar chain receptor is not particularly limited in type and number, as long as the antigen-binding molecule has a binding activity to the sugar chain receptor in a neutral pH range and as long as the binding activity to the sugar chain receptor in an acidic pH range is lower than the binding activity to the sugar chain receptor in the neutral pH range (page 156, paragraph [0205]). Thus, the claims encompass a method for producing a genus of antigen-binding molecules without any characteristic structural/functional features.
The specification discloses an antibody as an antigen-binding molecule (paragraph [0246] on page 191), in particular anti-human IL-6 receptor antibody (examples), and two pairs of sugar chain receptor binding domain and sugar chain receptor: a sugar chain receptor binding domain having N-linked sugar chain with a terminal galactose and an asialoglycoprotein receptor; a sugar chain receptor binding domain having N-linked sugar chain with a terminal mannose and a mannose receptor (pages 155 and 157). Example 2 discloses preparation of anti-human IL-6 receptor antibody being capable of binding in a pH-dependent manner and having a galactose-ended complex linked sugar chain introduced in variable region. However, no other antigen-binding molecules are disclosed.
The specification does not describe a sufficient variety of species to reflect the variation within the genus. The instant disclosure of an antigen-binding molecule comprising an anti-human IL-6 receptor antibody is insufficient to support the broad genus of antigen-binding molecules. Moreover, the specification does not disclose a correlation of structure and function (for example, the properties recited in claims 3-9) of the genus of recited antigen-binding molecules. Furthermore, the prior art does not provide compensatory structural or correlative teachings sufficient to enable one of skill to identify what other antigen-binding molecules might be. One of skilled in the art cannot envision the structure of other antigen-binding molecule with recited properties. Thus, the rejection is maintained.
Claim Rejections under 35 USC § 112 (b)
(i). The following is a quotation of the second paragraph of 35 U.S.C. 112:
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.
(ii). Claims 1, 3-9, 11-18, 23-27, and 93-97 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 1 recites in preamble “a method for producing an antigen-binding molecule”. However, the end step (f) of the method recites “processing the antigen-binding molecule recovered in (e) with a neuraminidase and/or beta galactosidase so as to form a sugar chain linked to the sugar chain linking motif, wherein the sugar chain comprises a terminal galactose or terminal mannose”. Thus, the preamble of the claim is inconsistent with the final step of the method of the claim, rendering the claim indefinite. Moreover, step (f) is not deemed to be capable of producing a sugar chain linked to the sugar chain linking motif by processing the antigen-binding molecule recovered in (e) with a neuraminidase and/or beta galactosidase. Claims 3-9, 11-18, 23-27, and 93-97 are rejected as dependent claims.
Claim Rejections under 35 USC§ 103(a)
(i). The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
(ii). Claims 1, 3-9, 11-18, 23-27, and 93-97 are rejected under 35 U.S.C. 103(a) as being unpatentable over either US 2002/0028486 A1 (Mar. 7, 2002) or Coloma et al (J. Immunol. 162:2162-2170, 1999) in view of Newkirk (Clin. Exp. Immunol. 106, 259-264, 1996).
US2002/0028486A1 teaches a method of introducing a carbohydrate recognition site into the variable region or a constant region of an antibody and the carbohydrate recognition site Asn-X-Thr/Ser (see, e.g., claims 1 and 24; paragraphs [0027-[0028] on page 3). US2002/0028486 A1 teaches an antibody prepared by the method (see, e.g., paragraph [0037] on page 4). US2002/0028486A1 teaches that an antibody includes all antibody isotypes, such as lgG (paragraph [0025] on page 3) and lgG4 (page 5, paragraph [0058]). The antibody binds high mannose (see, e.g., legend to Fig. 3A). US2002/0028486A1 further teaches that the carbohydrate recognition site may be introduced into the antibody by modifying or mutating an amino acid sequence so that the desired Asn-X-Thr/Ser sequence is obtained (page 3, paragraph [0030]).
Coloma et al teaches a method of introducing a carbohydrate recognition site Asn-X-Thr/Ser into the variable region or a constant region of an antibody (see, e.g., page 2163, left column, 2nd and 3rd paragraphs; page 2164, right column, 2nd paragraph). Coloma et al teaches an anti-dextran antibody, human IgG1, prepared by the method (see, e.g., page 2163, 1st paragraph of left column; Table 1 on page 2165). The antigen-binding domain (CDR3 of VH and CDR1 of VL) comprises two histidine residue (Table 1 on page 2165). The Fc region of the antibody comprises an FcRn binding domain that binds to FcRn.
With respect to the property of dependency of binding activity upon a pH condition recited in claims 3-9 and 15-18, either US2002/0028486 A1 or Coloma et al teach a method of producing the same antigen-binding molecule. Such a property recited in claims 3-9 and 15-18, would be inherently to the structure of antigen-binding molecule.
MPEP §2112 provides guidance as to the examiner's burden of proof for a rejection of claims under 35 U.S.C. 102 or 103 based upon the express, implicit, and inherent disclosures of a prior art reference. The case law clearly states that something which is old does not become patentable upon the discovery of a new property.
"[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art's functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. lreco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of a new use, new function or unknown property that is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977).
Further, the court has held that there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003) (rejecting the contention that inherent anticipation requires recognition by a person of ordinary skill in the art before the critical date and allowing expert testimony with respect to post-critical date clinical trials to show inherency); see also Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004)("[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention."); Abbott Labs v. Geneva Pharms., Inc., 182 F.3d 1315, 1319, 51 USPQ2d 1307, 1310 (Fed.Cir.1999). Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
While neither US2002/0028486 A1 nor Coloma et al explicitly teach the property of dependency of binding activity upon a pH condition recited in claims 3-9 and 15-18, case law establishes that the discovery of a previous unappreciated property of a prior art product, or of a scientific explanation for the prior art's functioning, does not render the old product patentably new to the discoverer.
Neither US 2002/0028486 A1 nor Coloma et al (J. Immunol. 162:2162-2170, 1999) teach (i) the step (f) of claim 1; and (ii) the limitations of claims 23-25.
However, it is well-known in the art that neuraminidase and β-galactosidase treatment can be used to make an antigen-binding molecule having a specific sugar chain and that an antibody having a high-mannose sugar chain is known to be prepared by sialidase (neuraminidase) and β-galactosidase treatment, by which galactose is removed from the sugar chain (Newkirk, Clin. Exp. Immunol. 106, 259-264, 1996). It would have been obvious for one skilled in the art to make an N- linked sugar chain comprising one, three or more terminal galactoses or to make an asialoglycoprotein receptor-binding domain with a reasonable expectation of success. One would have been motivated to do so because one of skill in the art routinely make variations in an N-linking sugar chain as needed.
Conclusion
No claims are allowed.
Advisory Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Ruixiang Li whose telephone number is (571) 272-0875. The examiner can normally be reached on Monday through Friday from 8:30 am to 5:00 pm. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Vanessa Ford, can be reached on (571) 272-0857. The fax number for the organization where this application or proceeding is assigned is (571) 273-8300.
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/RUIXIANG LI/Primary Examiner, Art Unit 1674 June 11, 2026
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