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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 5/6/2026 has been entered.
Claim Status
Claims 2 and 14-16 were canceled.
Claims 21-24 were added.
Claims 1, 3-13 and 17-24 are pending and under consideration.
Withdrawn Rejections
Rejection of Claims 1, 3-13 and 17-20 under 35 U.S.C. 103 as being unpatentable over Blais et al (WO2015/125118) in view of Blue et al (WO 2012/078482) and Hendericks et al (WO2010/142685) is withdrawn. Applicant amended the claim 1 to recite specific concentration which is not overlapping with concentration taught by prior art, thereby obviating this rejection. Furthermore, Applicant provided a persuasive argument that Blue et al. are directed towards reducing aggregation of polysaccharide-protein conjugates under agitation conditions and Blue et al. do not specifically recognize that the non-conjugated form of Protein D is subject to aggregation (Response filed 5/6/2026, page 6-7).
NEW - Claim Objections
(based on reconsideration)
Claim 1 is objected to because of the following informalities: “wherein Protein D is not conjugated to a polysaccharide” in line 5 should read “wherein the Protein D is not conjugated to a polysaccharide” because Protein D was already recited before the wherein-clause.
Appropriate correction is required.
Claims 1, 3-13 and 17-20 are objected to because of the following informalities: the preamble should read “The process according to claim X” to be consistent with new claims 21-24. Appropriate correction is required.
Claim 13 is objected to because of the following informalities: “according to the process of claim 1” should read “according to claim 1”. Appropriate correction is required.
Claim 13 is objected to because of the following informalities: “and subsequently freeze-drying” should read “further comprising subsequently freeze-drying” because the claimed process further comprises further active process step of freeze-drying. Appropriate correction is required.
NEW - Claim Rejections - 35 USC § 112
(necessitated by amendments)
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, 3-13 and 17-24 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 1 recites “mixing the Protein D polypeptide with sucrose to a concentration of 10 to 20% (w/v)”. It is unclear whether “concentration of 10 to 20% (w/v)” is the concentration of Protein D polypeptide or the concentration of sucrose because two components were recited but only one concentration was recited. Likewise, it is unclear whether “concentration of 0.5 to 1% (w/v)” in line 5 is the concentration of Protein D polypeptide or the concentration of poloxamer. If Applicant intends to recite concentrations of sucrose and poloxamer, it is suggested that Applicant amend
“mixing the Protein D polypeptide with sucrose to a concentration of 10 to 20% (w/v) and with poloxamer to a concentration of 0.5 to 1% (w/v), wherein Protein D is not conjugated to a polysaccharide”
TO
“mixing the Protein D polypeptide with sucrose and poloxamer, wherein final concentration of sucrose and poloxamer after mixing is 10 to 20% (w/v) sucrose and 0.5 to 1% (w/v) poloxamer, respectively, and wherein Protein D is not conjugated to a polysaccharide”.
Claim 3 recites “wherein the process comprises mixing the Protein D polypeptide with solution(s) comprising: (a) sucrose to a concentration of 10 to 15% (w/v), and (b) poloxamer to a concentration of 1% (w/v)”. It is not clear whether Applicant intends to recite that the process comprises mixing the Protein D polypeptide with solution(s) comprising: (a) 10 to 15% (w/v) sucrose, and (b) 1% (w/v) poloxamer” (i.e. concentration before mixing with Protein D polypeptide) because claim 3 recites solution comprising (a) sucrose, and (b) poloxamer. In other words, it is unclear if Applicant intends to recite the concentration before or after mixing with Protein D. If Applicant intends to recite the concentration after mixing with Protein D, it is suggested that Applicant amend
“wherein the process comprises mixing the Protein D polypeptide with solution(s) comprising: (a) sucrose to a concentration of 10 to 15% (w/v), and (b) poloxamer to a concentration of 1% (w/v)”
TO
“wherein the process comprises mixing the Protein D polypeptide with solution(s) comprising: (a) sucrose and (b) poloxamer, wherein final concentration of sucrose and poloxamer is 10 to 15% (w/v) sucrose and 1% (w/v) poloxamer, respectively, after mixing the Protein D polypeptide with the solution.”
Dependent claims are also rejected because they depend from claim 1 and contain same claim limitation as claim 1.
NEW - Claim Rejections - 35 USC § 112
(based on reconsideration)
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, 3-13 and 17-24 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.
MPEP § 2163 states that 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, 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. A “representative number of species” means that the species which are adequately described are representative of the entire genus. See, e.g., AbbVie Deutschland GMBH v. Janssen Biotech, 759 F.3d 1285, 111 USPQ2d 1780 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention. “Functional” terminology may be used “when the art has established a correlation between structure and function” but “merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing one has invented a genus and not just a species.” Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 598 F3d 1336, 94 USPQ2d 1161, 1171 (Fed Cir. 2010).
Claims are drawn to a process for preparing a liquid composition comprising a Protein D polypeptide, wherein the Protein D polypeptide has at least 90% identity to SEQ ID NO: 2, wherein the process comprises; mixing the Protein D polypeptide with sucrose to a concentration of 10 to 20% (w/v) and with poloxamer to a concentration of 0.5 to 1% (w/v), wherein Protein D is not conjugated to a polysaccharide.
With regard to claim limitation “at least 90% identity to SEQ ID NO: 2” of instant claim 1, instant specification disclosed only two species of protein D polypeptide SEQ ID NO: 1 and SEQ ID NO: 2 at page 40-41. However, the specification fails to provide adequate written description for the protein D polypeptide having at least 90% identity to SEQ ID NO: 2.
Instant SEQ ID NO: 2 has 348 amino acids (page 41 of instant specification). Therefore, the protein D having at least 90% identity to SEQ ID NO: 2 can have mutations at 34 amino acid positions. The possible number of combinations of selecting 34 positions out of 348 amino acids is (348,34) = 348! / ((348-34)! x 34!) = (348 x 347 x 346 x … x 316 x 315) / (34 x 33 x 32 x … x 3x2x1). For each combination, the possible substitutions at 34 positions are 2034 – 1 (wild type). Therefore, instant claim 1 encompasses practically infinite number of protein D polypeptides. Only two species of protein D polypeptides disclosed by instant specification cannot be considered as a representative number of species falling within the scope of genus encompassing practically infinite number of protein D polypeptides. Just because protein D polypeptide having SEQ ID NO: 2 does not make visible particles in solutions comprising protein stabilizer sucrose and poloxamer does not means that any possible mutation variants having at least 90% identity to SEQ ID NO: 2 will not make visible particles in solutions. This is further supported by following example well known in the art.
In the field of protein modification technology, a change of a single amino acid residue may change the properties of the protein. Sickle cell anemia, for example, results from a mutation in just one of 574 amino acids. For example, Prengler et al (Ann Neurol 2002;51:543-552; PTO-892) teaches that one amino acid substitution valine for glutamic acid at the sixth position of the beta-globin chain cause sickle cell anemia (page 544, left column, third paragraph). Because Prengler teaches that a single amino acid change can cause dramatic change in protein solubility and because instant claim 1 even encompasses variant of SEQ ID NO: 2 comprising hydrophobic amino acids at all 34 allowed positions out of 348 amino acids of protein D as discussed above, one of ordinary skill in the art would not be able to predict that all these variants will be soluble in the solution comprising sucrose and poloxamer just because instant specification showed that polypeptide of SEQ ID NO: 2 is soluble in this condition.
Furthermore, instant specification did not show that all possible variants encompassed by instant claim 1 will have same function of boosting immune response against antigens as protein D of SEQ ID NO: 2. Witkowski et al (Biochemistry 38:11643-11650, 1999; PTO-892) teach that one conservative amino acid substitution transforms a β-ketoacyl synthase into a malonyl decarboxylase and completely eliminates β-ketoacyl synthase activity. Seffernick et al., (Bacteriol. 183(8): 2405-2410, 2001; PTO-892) teach that two naturally occurring Pseudomonas enzymes having 98% amino acid sequence identity catalyze two different reactions: deamination and dehalogenation, therefore having different function. It is not always possible to make variants that retain activity if the regions have been altered.
“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). 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.
Structural features that could distinguish a “variant” in the genus from others in the protein class are missing from the disclosure and the claims. No common structural attributes identify the members of the genus. The general knowledge and level of skill in the art do not supplement the omitted description, because specific, not general guidance is needed.
The disclosure therefore does not show that applicant was in possession of the necessary common attributes or features possessed by the members of the claimed genus. Accordingly, the skilled artisan would not recognize that applicants were in possession of the invention as broadly claimed at the time the application was filed.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHEOM-GIL CHEONG whose telephone number is (571)272-6251. The examiner can normally be reached Monday - Friday 9:00 am - 5:00 pm.
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, Misook Yu can be reached at 571-272-0839. 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.
/CHEOM-GIL CHEONG/Examiner, Art Unit 1645
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
Prosecution Insights