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 .
Response to Amendment
The Amendment filed 05/11/2026 has been entered. Applicant’s amendments are in response to in the Non-Final Office Action mailed 12/11/2025. Applicant’s claims have been amended in the following manner: independent claims 1 and 3 have been amended with a “1 mg/mL” concentration limitation, independent claim 2 further specifies the condition of comparing dynamic viscosities (i.e., morphology, crystal size, instrument configuration), and claim 5 incorporates a minor semantic edit. A new ground of rejection is prompted by the amendment. The amendments find support in Applicant’s Specification (pg 38 and 39).
The following objections/rejections are withdrawn: none.
The Examiner further acknowledges the following:
Claims 1-3, 5-6, 8-9, 11, 13, 17, 19-21, 23-24, 32-33, 35-37, and 76-77 are pending.
Claims 1-3, 5-6, 8-9, 11, 13, 17, 19-21, 23-24, 32-33, 35-37, and 76-77 are presented for examination and rejected as set forth below.
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.
Claim 2 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential elements, such omission amounting to a gap between the elements. See MPEP § 2172.01. The omitted elements are: specifying the “carrier encapsulation environment” that is different. Only stating a difference in “carrier encapsulation environment” provides an unlimited choice of modification of the environment (e.g., ingredients, amounts, structure, etc.), as compared to the general composition of “crystals comprising a solid form of a polypeptide.”
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-3, 5-6, 8-9, 11, 13, 17, 19-21, 23-24, 32-33, 35-37, and 76-77 are rejected under 35 U.S.C. 103 as being unpatentable over Chandrashekhar (US20020151650A1), and in further view of Yang (PNAS, 2003; cited on the IDS filed 05/25/2023), Ickenstein (Therapeutic Delivery, 2018), and Shenoy (US20180333493A1).
Applicant’s claims (independent claim 1) are directed to a composition, comprising a hydrogel particle and a crystal comprising the solid form of a polypeptide at least partially encapsulated by the hydrogel particle. Independent claims 2 and 3 attempt to limit this general concept from a different frame of reference by employing alternate limitations. Applicant significantly adds concentration limitation of “greater than or equal to 1 mg/mL” (instant claims 1 and 3), and “same crystal morphology and crystal size distribution under conditions having the same instrument configuration and a temperature and shear rate each within 5%, but where the carrier encapsulation environment is different” (instant claim 2).
Note that claims 1-3 appear very broad, and the broadest reasonable interpretation will be taken for each. Furthermore, any expectation of unexpected results to break the obviousness of a rejection must be commensurate in scope with the claim language. In this case, the claim language appears far broader than the teachings of the examples of the Specification. Any reliance on unexpected results to demonstrate non-obviousness should meet the breadth of the instant claim scope.
Additionally, the Examiner has noted the very specific method of making that relies on a specific centrifugal extrusion process (Example 6, figure 25). See Examples 2 and 3 (on pg 60 of the Specification) for an illustrative example of the manufacturing process. Also, “crystal comprising a solid form of a polypeptide” is understood to include species such as complexes (e.g., solid form of pembrolizumab complexed to caffeine as on pg 5 of the Specification, lines 16-19). The hydrogel particles are discussed, for example, in terms of microspheres (pg 3, Specification pg 9-10, pg 52, ‘conclusions’) and polymers such as polysaccharides, polyalkylene oxides, etc. (pg 2-3).
Chandrashekhar teaches gels that comprises an antibody [0064], for the use of drug delivery (abstract).
Regarding claim 1, 3, 5-6, 8, 33, and 35: Chandrashekhar teaches a gel (reads on hydrogel) that comprises an antibody [0064], useful for therapeutics (abstract). Chandrashekhar teaches macromers that are covalently or non-covalently crosslinkable to form hydrogels, such that the macromers are provided in a carrier [0025]. The bioactive molecules are encapsulated to achieve sustained drug release [0025, 0139].
Regarding claim 9: Chandrashekhar teaches polymer chains of at least 4000 Daltons (i.e., the polymer can be more than 4 kDa) [0030], where the initial polymer molecular weight influences degradation rate, suggesting room for optimization [0056].
Regarding claims 11, 13, and 17: Chandrashekhar teaches cross-linked polyalkylene oxides, polysaccharides, and polypeptides [0025, 0040].
Regarding claims 19-21 and 23-24: Chandrashekhar teaches that the macromers of the gel can form microspheres that generally have a diameter from the nanometer range to 5 mm [0071]. Note that "[A] prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness." In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003) (see 2144.05(I)).
In summary, Chandrashekhar teaches antibody proteins encapsulated in hydrogel particles. However, Chandrashekhar does not explicitly teach incorporation of “a crystal comprising a solid form of a polypeptide” (instant claim 1), the effect where the dynamic viscosity is lowered between a composition and an aqueous suspension under the same instrument configuration (instant claim 2), low (<10 wt%) aggregation (instant claim 3), low dynamic viscosity (instant claim 32), and the specified antibody type (instant claims 36-37).
Yang teaches a composition comprising crystalline monoclonal antibodies for subcutaneous delivery (abstract). Yang further teaches that crystalline monoclonal antibodies (mAbs) overcome the issues of high viscosity, aggregation, and poor stability of high concentration preparations (compared to non-crystalline mAbs) (pg 6934, paragraph 1) through an IgG mAb example (pg 6934, paragraph 3; pg 6938, “results and discussion”). Finally, Yang teaches a crystalline antibody viscosity of 26 cps (or 0.26 Pa-s) (at 150 mg/mL concentration), and no aggregation (reads on less than or equal to 10 wt% of the crystals are aggregated) at 200 mg/mL (pg 6938, paragraphs 3 and 4).
With respect to polypeptide crystalline formulations, Yang teaches concentrations from 0-250 mg/mL as obvious (pg 6936, Figure 3) (i.e., reads on the newly amended greater than or equal to 1 mg/mL of instant claims 1 and 3).
Shenoy teaches high concentration protein formulations (e.g., 150-300 mg/mL, Shenoy – claim 1) where the viscosity can be lowered by viscosity reducing agents (i.e. “excipient” that is part of the carrier and thus, changes the “carrier encapsulation environment” of instant claim 2) (abstract, figure 3). Shenoy teaches viscosities less than 50 cP (i.e., 0.05 Pa-s), where the excipient provides approximately a 5-10 fold reduction in viscosity (reads on “at least 1.1 times lower”) of the solution (Figure 3, Shenoy – claim 1). Shenoy teaches the desirability to reduce viscosity and/or aggregation in protein formulations for drug delivery [0002]. Notably, Shenoy teaches solutions and suspensions (Shenoy - claim 41, [0142]), where the viscosity-reducing excipient and effect is applicable (Shenoy – claims 1-3, 12-15, 27-34).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the hydrogel antibody drug delivery formulation of Chandrashekhar with the crystalline mAb of Yang because there is motivation to substitute a crystalline mAb for a regular antibody such that crystalline mAbs overcome the issues of high viscosity, aggregation, and poor stability of high concentration preparations (compared to non-crystalline mAbs) (pg 6934, paragraph 1). This is exemplified by the absence of aggregation and low viscosity of high concentration crystalline mAb compositions of Yang (pg 6934, paragraph 3). Thus, if the input crystalline polypeptide demonstrates no aggregation (reads on less than or equal to 10 wt% of the crystals are aggregated) at 200 mg/mL (pg 6938, paragraphs 3 and 4), a PHOSITA would expect less than or equal to 10 wt% aggregation of a crystalline polypeptide formulation, comprising one or more hydrogels in association (reads on instant claim 3).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify a crystalline antibody formulation, as taught by Chandrashekhar and Yang, that incorporates excipients that reduce the viscosity of the resulting formulation (as taught by Shenoy) such that the viscosity of the composition would be lower than an aqueous suspension having equivalent concentration of crystalline polypeptides (i.e., Yang teaches 200 mg/mL and Shenoy teaches 150-300 mg/mL, as appropriate drug delivery concentrations) (reads on instant claim 2). The incorporation of viscosity reducing excipients is motivated because Shenoy teaches the desirability to reduce viscosity and/or aggregation in protein formulations for drug deliver [0002]. Notably, Shenoy teaches solutions and suspensions (Shenoy - claim 41, [0142]), where the viscosity-reducing excipient and effect is applicable (Shenoy – claims 1-3, 12-15, 27-34). Thus, the combined Prior Art teaches a scenario where a crystalline polypeptide in combination with a viscosity reducing excipient (reading on the BRI of “where the carrier encapsulation environment is different”) has a lower viscosity compared to an aqueous suspension of that peptide (reads on instant claim 2). Additionally, a PHOSITA would not expect the carrier comprising an additional “hydrogel” in no particular amount (instant claim 6) to affect the outcome of the viscosity reduction.
In addition, Ickenstein has directly suggested improving drug loading capacity in hydrogels by using crystalline proteins (pg 227-228, ‘conclusion & future perspective’), explicitly stating a direct motivation of replacing the antibodies of Chandrashekhar’s hydrogels with the crystalline antibodies of Yang. Thus, the discussed Prior Art are all interested in different aspects of improving mAb delivery through reduction of viscosity/aggregation and improvement in stability and teaching crystalline mAbs and hydrogel formulations as ways to accomplish this.
With respect to the totality of instant claim 2, from a perspective of obviousness (i.e., “wherein the composition has a dynamic viscosity that is at least 1.1 times lower than that of an aqueous suspension having an equivalent concentration of crystalline polypeptides crystals comprising a solid form of a polypeptide of the same crystal morphology and crystal size distribution having the same instrument configuration and a temperature and shear rate each within 5%, but where the carrier encapsulation environment is different”),
Shenoy teaches that a carrier comprising compounds can interact with proteins to lower the viscosity of mAb formulations, making the viscosity reduction of at least 1.1 obvious. Furthermore, incorporation of a hydrogel to the “aqueous suspension” vs. “composition” (i.e., these things can be the same thing, because “composition” is a generic term for a mixture of ingredients) would not change the expectation of this kind of viscosity reduction.
For crystal morphology and crystal size distribution of a crystalline polypeptide inside and outside of a “carrier” (i.e., a hydrogel in claim 6), a PHOSITA would expect these properties to remain the same because Chandrashekhar teaches antibody formulations [0064], within a hydrogel (abstract) as typical of the art, and furthermore, Yang teaches crystalline antibodies exhibit more stability compared to amorphous antibodies (pg 6934), inclusive of consideration for crystalline morphology (pg 6938, paragraph 3) and size (including potential aggregation of fragmentation) (pg 6938, paragraphs 3-4). Thus, from a point of obviousness, one would not expect the morphology and size of a crystalline antibody to significantly change inside and outside of a “carrier” (or hydrogel).
With respect to the newly limited same instrument configuration, temperature, and shear rate (of the dynamic viscosity in instant claims 2 and 32), the U.S. Patent Office is not equipped with analytical instruments to test prior art compositions for the infinite number of ways that a subsequent applicant may present previously unmeasured characteristics. When as here, the prior art appears to contain the exact same ingredients and applicant's own disclosure supports the suitability of the prior art composition as the inventive composition component, the burden is properly shifted to applicant to show otherwise. “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).
Claims 1, 8-9, 11, 13, 17, 19-21, 23-24, 33, and 35 are rejected under 35 U.S.C. 103 as being unpatentable over Chandrashekhar (US20020151650A1), in further view of Alvarez (WO2017191323A1; provided in Japanese Office Action from newly filed IDS on 10/24/2025) and Yang (PNAS, 2003; cited on the IDS filed 05/25/2023).
As discussed above, Chandrashekhar teaches the specific limitations of claims 1, 8-9, 11, 13, 17 19-21, 23-24, 33, and 35. In particular, Chandrashekhar teaches proteins (e.g., an antibody) encapsulated in hydrogel particles.
However, Chandrashekhar does not explicitly teach incorporation of “a crystal comprising a solid form of a polypeptide” into the hydrogel formulation (instant claim 1).
Alvarez teaches pharmaceutically active protein crystals (such as insulin) within a hydrogel formulation (abstract) at a final concentration of 5 mg/mL (see Example 2 - Insulin protein in di-alanine gel), which is useful for drug delivery by injection (pg 13, section 5.1). Alvarez teaches the hydrogel can be cross-linked polymer that is made of agarose, gelatin, PEG for example (Alvarez – claims 1-2), and that protein crystals can also be monoclonal antibodies (Alvarez – claim 10).
Yang teaches a composition comprising crystalline monoclonal antibodies for subcutaneous delivery (abstract). Yang further teaches that crystalline monoclonal antibodies (mAbs) overcome the issues of high viscosity, aggregation, and poor stability of high concentration preparations (compared to non-crystalline mAbs) (pg 6934, paragraph 1) through an IgG mAb example (pg 6934, paragraph 3; pg 6938, “results and discussion”). Finally, Yang teaches a crystalline antibody viscosity of 26 cps (or 0.26 Pa-s) (at 150 mg/mL concentration) compared to 275 cps (at 150 mg/mL concentration) for soluble antibody (pg 6936, Fig 3), and no aggregation (reads on less than or equal to 10 wt% of the crystals are aggregated) at 200 mg/mL (pg 6938, paragraphs 3 and 4). With respect to polypeptide crystalline formulations, Yang teaches concentrations from 0-250 mg/mL as obvious (pg 6936, Figure 3) (i.e., reads on the newly amended greater than or equal to 1 mg/mL of instant claims 1 and 3).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the hydrogel particles of Chandrashekhar to incorporate a crystalline polypeptide (such as an antibody or insulin [0064]), as taught by Alvarez (demonstrating crystalline insulin incorporation into a hydrogel), at a concentration of greater than or equal to 1 mg/mL, as taught by Yang, because Alvarez teaches that crystalline insulin (reads on “crystals comprising the solid form of the polypeptide” of instant claim 1) with a hydrogel formulation can provide unique pharmacokinetic behavior (i.e., release profile) (Example 5 on pg 13-16) and better stability (pg 1-2, ‘background of invention’).
Response to Arguments
Applicants arguments, see pg 6-11, filed 05/11/2026, with respect to the 103 rejection of claims 1-3, 5-6, 8-9, 11, 13, 17, 19-21, 23-24, 32-33, 35-37, and 76-77 under rejection have been fully considered but they are not persuasive. The 103 rejection has been modified with respect to amendments made to the claim set and new added claims.
On page 6, Applicant discusses changes made to overcome the 112(b) rejections which has resulted in a modified 112(b) rejection based on the omission of essential elements (see 112(b) rejection above for details).
On page 7-8, Applicant discusses claims 1 and 3.
Applicant argues that Ickenstein teaches away from the modification presented in the 103 rejection of the Application through “numerous perceived disadvantages and possible pitfalls”, including “possible interactions of proteins and with gel components.” Furthermore, just because an option has been described as less advantageous or desirable doesn’t negate the obviousness of its use: An obvious composition suggested as inferior does not afford patentability: In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). “A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use.” A PHOSITA would not be deterred by this teaching but would be invited to develop new formulation technologies to address the problem. In order to teach away from a proposed modification, the art must “criticize, discredit, or otherwise discourage the solution claimed….” In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). The art does not criticize, discredit, or otherwise discourage the modification proposed by the Examiner. However, Ickenstein has directly suggested improving drug loading capacity in hydrogels by using crystalline proteins (pg 227-228, ‘conclusion & future perspective’), explicitly stating a direct motivation of replacing the antibodies of Chandrashekhar’s hydrogels with the crystalline antibodies of Yang.
Additionally, Applicant has not provided any objective evidence that the formulation of a crystalline mAb within a hydrogel is beyond the abilities of a person having ordinary skill in the art technically (or operationally) unachievable (i.e., crystalline antibodies are no longer “intact, stable, and/or functional”), and therefore frustrating the purpose of Chandrashekar’s disclosure. Furthermore, Alvarez provides an embodiment of a crystalline antibody within a hydrogel formulation, directly counteracting this point. Thus, within the obviousness analysis, the proposed combination is based on a reasonable expectation of success.
Furthermore, Chandrashekhar teaches antibody formulations [0064], within a gel (i.e., hydrogel) (abstract) as typical of the art, and furthermore, Yang teaches crystalline antibodies exhibit more stability compared to amorphous antibodies (pg 6934), inclusive of consideration for crystalline morphology (pg 6938, paragraph 3) and size (including potential aggregation of fragmentation) (pg 6938, paragraphs 3-4). Thus, from a point of obviousness, one would expect the limitations of independent claims 1 and 3 as entirely within the grasp of PHOSITA, based on the available combined Prior Art, at the time of filing. As a far as reasonable expectation of success: “Applicants are reminded that obviousness does not require absolute predictability. See In re Rinehart, 531 F.2d 1048, 189 USPQ 143 (CCPA 1976) (indicating that evidence showing there was no reasonable expectation of success may support a conclusion of nonobviousness).” Thus, there is sufficient rationale and motivation to support the proposed reference combination of the 103 rejection, as obvious, based on the available Prior Art, at the time of fling. Applicant has not provided any evidence contradicting the obviousness of the combination.
On page 8-9, Applicant discusses claim 2 (highlighting “where the carrier encapsulation environment is different”). With respect to the totality of instant claim 2, from a perspective of obviousness (i.e., “wherein the composition has a dynamic viscosity that is at least 1.1 times lower than that of an aqueous suspension having an equivalent concentration of crystalline polypeptides crystals comprising a solid form of a polypeptide of the same crystal morphology and crystal size distribution having the same instrument configuration and a temperature and shear rate each within 5%, but where the carrier encapsulation environment is different”),
Shenoy teaches that a carrier comprising compounds can interact with proteins to lower the viscosity of mAb formulations, making the viscosity reduction of at least 1.1 obvious. Furthermore, incorporation of a hydrogel (which is not written into claim 2, but appears in claim 6), such as in the polypeptide/antibody hydrogel formulation of Chandrashekar (abstract, [0064]), would not change the expectation of this kind of general viscosity reduction caused by a viscosity-reducing agent. – Additionally, Applicant has not provided objective data to invalidates the Examiner’s analysis. Applicant has not argued unexpected results commensurate in claim scope to demonstrate non-obviousness.
Furthermore, as evidenced by Schermeyer (MABS, 2017), mAb viscosity can be modulated (i.e., generally reduced in Figure 3)) by a variety of additives (e.g., glycine, Na2SO4, and 0.4 m/V% PEG4000, in which PEG4000 is a known component of hydrogel structures) through a mechanism of disrupting mAb-mAb interactions that is present in concentrated formulations (pg 1179, col 1, and pg 1173, Figure 3). It is noted that Yang’s crystalline antibody formulations contain PEG400 and PEG8000 additives (pg 6936, Fig 3), Chandrashekar makes obvious the use of PEG-based copolymers [0004, 0109], Alvarez teaches a PEG hydrogel protein crystal composition (Alvarez – claims 1-2), whereby the PEG additive would have the ability to modulate the formulation viscosity based on additive concentration applied, as evidenced by Schermeyer’s work on PEG4000. Thus, the viscosity reduction of claim 2 would be an expected result of changing the “carrier encapsulation environment” under selected circumstances (i.e., whereby the claim language is not specific under what circumstances would lead to the viscosity reduction).
For crystal morphology and crystal size distribution of a crystalline polypeptide inside and outside of a “carrier” (i.e., a hydrogel in claim 6), a PHOSITA would expect these properties to remain the same because Chandrashekhar teaches antibody formulations [0064], within a hydrogel (abstract) as typical of the art, and furthermore, Yang teaches crystalline antibodies exhibit more stability compared to amorphous antibodies (pg 6934), inclusive of consideration for crystalline morphology (pg 6938, paragraph 3) and size (including potential aggregation of fragmentation) (pg 6938, paragraphs 3-4). Thus, from a point of obviousness, one would not expect the morphology and size of a crystalline antibody to significantly change inside and outside of a “carrier” (or hydrogel). – Additionally, Applicant has not provided objective data to invalidates the Examiner’s analysis.
With respect to the newly limited same instrument configuration, temperature, and shear rate (of the dynamic viscosity in instant claims 2 and 32), the U.S. Patent Office is not equipped with analytical instruments to test prior art compositions for the infinite number of ways that a subsequent applicant may present previously unmeasured characteristics. When as here, the prior art appears to contain the exact same ingredients and applicant's own disclosure supports the suitability of the prior art composition as the inventive composition component, the burden is properly shifted to applicant to show otherwise. “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).
Note that with regard to the combined limitations of independent claim 2, all elements of each prior art reference need not read on the claimed invention, rather, the proper test for obviousness is what the combined teachings would have suggested to a person of ordinary skill in the art. In re Kotzab, 217 F.3d 1365, 1370 (Fed. Cir. 2000).Thus, instant claim 2 is obvious based on the known interaction of viscosity-reducing agents (that are dissolved into a carrier environment that surrounds the polypeptide) with polypeptides that reduce the viscosity of the overall polypeptide formulations.
In order to demonstrate non-obviousness, Applicant could provide objective data invalidating the Examiner’s analysis or may show an unexpected result that is commensurate with the claim scope (i.e., the claimed composition should be able to consistently meet the claimed functional properties as demonstrated by objective data).
On page 9-10, Applicant discusses the alternate rejection (in relation to claim 1). In terms of the combining of Chandrashekhar and Alvarez. As discussed previously, note that neither reference is required to teach all elements (i.e., it is the combined teachings). All elements of each prior art reference need not read on the claimed invention, rather, the proper test for obviousness is what the combined teachings would have suggested to a person of ordinary skill in the art. In re Kotzab, 217 F.3d 1365, 1370 (Fed. Cir. 2000). Furthermore, limiting the understanding of Alvarez to Example 5 directed to insulin is a deficient reading of Alvarez as a whole who teaches crystalline polypeptides in hydrogel formulations (abstract), whereby antibodies are also discussed as obvious for incorporation (Alvarez – claim 10).
With regard to reasonable expectation of success: “Applicants are reminded that obviousness does not require absolute predictability. See In re Rinehart, 531 F.2d 1048, 189 USPQ 143 (CCPA 1976) (indicating that evidence showing there was no reasonable expectation of success may support a conclusion of nonobviousness).” Furthermore, Applicant has not provided evidence that unpredictability of the art to challenge the obviousness of the modification.
With regard to Applicant’s argument of the Office’s line of “because Alvarez teaches that crystalline mAb” of the previous Office Action, this is a typo (which has been fixed above) from a copy-paste workflow. Alvarez clearly teaches crystalline insulin (see reference), which meets the limitation so the crystalline polypeptide of instant claim 1. But also note that Alvarez as a whole teaches crystalline polypeptides in hydrogel formulations (abstract), whereby antibodies are also discussed as obvious for incorporation (Alvarez – claim 10). Furthermore, Chandrashekhar teaches mAb and proteins (including insulin [0064]), whereby it is the combined teachings that represent the Prior Art of an obviousness analysis. All elements of each prior art reference need not read on the claimed invention, rather, the proper test for obviousness is what the combined teachings would have suggested to a person of ordinary skill in the art. In re Kotzab, 217 F.3d 1365, 1370 (Fed. Cir. 2000). Thus, appropriate rationale has been provided in the 103 rejection to combine references.
On page 10-11, Applicant concludes including comments on dependent claims in relation to the independent claims. Note that independent claims 1-3 remain under rejection, and no dependent limitation resolves the obviousness taught by the Prior Art.
Correspondence
Applicant's amendment necessitated the new ground of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
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/R.P./Examiner, Art Unit 1614 5/28/2026
/SEAN M BASQUILL/Primary Examiner, Art Unit 1614
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